86 results on '"Madalina Uzunov"'
Search Results
2. CAR T-cell therapy for central nervous system lymphomas: blood and cerebrospinal fluid biology, and outcomes
- Author
-
Claire Lacan, Jonathan Caron, Nadine Tarantino, Baptiste Fouquet, Mustapha Cherai, Christophe Parizot, Véronique Morel, Laetitia Souchet, Madalina Uzunov, Guy Gorochov, Stéphanie Nguyen-Quoc, Elise Sourdeau, Vincent Vieillard, Makoto Miyara, Angélique Vinit, Silvia Solorzano, Carole Soussain, Caroline Houillier, Carole Metz, Brigitte Autran, Elena Litvinova, Magali Le Garff-Tavernier, Françoise Norol, Damien Roos-Weil, Sylvan Choquet, Amélie Guihot, and Marine Baron
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
- Full Text
- View/download PDF
3. Impact of central nervous system involvement in adult patients with Philadelphia-negative acute lymphoblastic leukemia: a GRAALL-2005 study
- Author
-
Corentin Orvain, Sylvain Chantepie, Xavier Thomas, Martine Escofrre-Barbe, Francoise Huguet, Yohan Desbrosses, Gaelle Guillerm, Madalina Uzunov, Thibaut Leguay, Sarah Barbieux, Norbert Vey, Patrice Chevallier, Jean-Valere Malfuson, Stephane Lepretre, Michael Baumann, Murat Aykut, Abdelaziz Chaib, Magalie Joris, Hacene Zerazhi, Georg Stussi, Jacques Chapiro, Celine Berthon, Caroline Bonmati, Eric Jourdan, Diana Carp, Amb roise Marcais, Maria-Pilar Gallego-Hernanz, Iona Vaida, Karin Bilger, Alban Villate, Florence Pasquier, Yves Chalandon, Sebastien Maury, Veronique Lheritier, Norbert Ifrah, Herve Dombret, Nicolas Boissel, and Mathilde Hunault-Berger.
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Whereas the prognosis of adult patients with Philadelphia-negative acute lymphoblastic leukemia (ALL) has greatly improved since the advent of pediatric-inspired regimens, the impact of initial central nervous system (CNS) involvement has not been formerly re-evaluated. We report here the outcome of patients with initial CNS involvement included in the pediatric-inspired prospective randomized GRAALL-2005 study. Between 2006 and 2014, 784 adult patients (aged 18-59 years) with newly diagnosed Philadelphia-negative ALL were included, of whom 55 (7%) had CNS involvement. In CNSpositive patients, overall survival was shorter (median 1.9 years vs. not reached, HR=1.8 [1.3-2.6], P
- Published
- 2023
- Full Text
- View/download PDF
4. Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia
- Author
-
Fotini Kostopoulou, Clementine Gabillaud, Elise Chapiro, Beatrice Grange, Julie Tran, Simon Bouzy, Michael Degaud, Hussein Ghamlouch, Magali Le Garff‐Tavernier, Karim Maloum, Sylvain Choquet, Veronique Leblond, Jean Gabarre, Anne Lavaud, Veronique Morel, Damien Roos‐Weil, Madalina Uzunov, Romain Guieze, Olivier A. Bernard, Santos A. Susin, Olivier Tournilhac, Florence Nguyen‐Khac, and the French Innovative Leukemia Organization (FILO) group
- Subjects
2p gain ,chronic lymphocytic leukemia ,drug resistance ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The different types of drug resistance encountered in chronic lymphocytic leukemia (CLL) cannot be fully accounted for by the 17p deletion (and/or TP53 mutation), a complex karyotype (CK), immunoglobulin heavy‐chain variable region genes (IGHV) status and gene mutations. Hence, we sought to assess the associations between recurrent genomic abnormalities in CLL and the disease's development and outcome. To this end, we analyzed 64 samples from patients with CLL and gain of the short arm of chromosome 2 (2p+), which is frequent in late‐stage and relapsed/refractory CLL. We found that fludarabine/cyclophosphamide/rituximab (a common first‐line treatment in CLL) is not effective in removing the 2p+ clone ‐ even in samples lacking a CK, the 17p deletion or unmutated IGHV. Our results suggest strongly that patients with CLL should be screened for 2p+ (using karyotyping and fluorescence in situ hybridization) before a treatment option is chosen. Longer follow‐up is now required to evaluate bendamustine‐rituximab, ibrutinib, and idelalisib‐rituximab treatments.
- Published
- 2019
- Full Text
- View/download PDF
5. Aspergillus PCR in Bronchoalveolar Lavage Fluid for the Diagnosis and Prognosis of Aspergillosis in Patients With Hematological and Non-hematological Conditions
- Author
-
Sébastien Imbert, Isabelle Meyer, Martine Palous, Jean-Yves Brossas, Madalina Uzunov, Feriel Touafek, Frédérick Gay, Valéry Trosini-Desert, and Arnaud Fekkar
- Subjects
Aspergillus fumigatus ,PCR ,fungal infection ,solid organ transplant ,hematology ,galactomannan ,Microbiology ,QR1-502 - Abstract
Objectives: We evaluated the usefulness of an Aspergillus fumigatus quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis.Methods: This 4-year retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants. Thirty-five patients had proven/probable aspergillosis and thirteen had chronic non-invasive aspergillosis. We compared PCR, galactomannan index and mycological analysis of BAL.Results: For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity. Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively. Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively. Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms. Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (p < 0.05).Conclusion: Our results indicate that Aspergillus PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA. It is likewise an interesting tool for the diagnosis of non-invasive forms.
- Published
- 2018
- Full Text
- View/download PDF
6. Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy
- Author
-
Tereza Coman, Emmanuel Bachy, Mauricette Michallet, Gérard Socié, Madalina Uzunov, Jean Henri Bourhis, Simona Lapusan, Alain Brebion, Stéphane Vigouroux, Sébastien Maury, Sylvie François, Anne Huynh, Bruno Lioure, Ibrahim Yakoub-Agha, Olivier Hermine, Noël Milpied, Mohamad Mohty, and Marie Thérèse Rubio
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Optimal salvage treatment for multiple myeloma relapsing after allogeneic stem cell transplantation remains to be determined. Usually, such patients have been heavily pre-treated and present at relapse with a relatively refractory disease. Immunomodulatory properties of lenalidomide may be beneficial by facilitating a graft-versus-myeloma effect after allogeneic stem cell transplantation. However, the safety of such treatment is still under debate. We conducted a multicenter retrospective study and included 52 myeloma patients receiving lenalidomide alone or in combination with dexamethasone as salvage therapy after allogeneic stem cell transplantation. The first aim was to assess the efficacy and tolerance of this drug. The second aim was to evaluate its potential immunomodulatory effects evaluated on the occurrence of acute graft-versus-host disease under treatment. In this cohort, we show that lenalidomide can induce a high response rate of 83% (including 29% complete response). On lenalidomide therapy, 16 patients (31%) developed or exacerbated an acute graft-versus-host disease, which was the only factor significantly associated with an improved anti-myeloma response. Side effects were mostly reversible, whereas 2 deaths (4%) could be attributed to treatment toxicity and to graft-versus-host disease, respectively. With a median follow up of 16.3 months, the median overall and progression free survival were 30.5 and 18 months, respectively, independently of the occurrence of acute graft-versus-host disease under lenalidomide. Lenalidomide can induce high response rates in myeloma relapsing after allogeneic stem cell transplantation at least in part by triggering an allogeneic anti-myeloma response. Induced graft-versus-host disease has to be balanced against the potential benefit in terms of disease control. Further immunological studies would help us understand lenalidomide immunomodulatory activity in vivo.
- Published
- 2013
- Full Text
- View/download PDF
7. Younger donor’s age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
- Author
-
Claire Fabre, Serge Koscielny, Mohamad Mohty, Nathalie Fegueux, Didier Blaise, Natacha Maillard, Reza Tabrizi, Mauricette Michallet, Gérard Socié, Ibrahim Yakoub-Agha, Frédéric Garban, Madalina Uzunov, Sylvie François, Nathalie Contentin, Simona Lapusan, and Jean-Henri Bourhis
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).Design and Methods This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.Results Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.Conclusions We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies.
- Published
- 2012
- Full Text
- View/download PDF
8. Norovirus and sapovirus infections after allogeneic hematopoietic stem cell transplantation: is it worth it to look for them?
- Author
-
Arthur Mageau, Katia Ambert-Balay, David Boutolleau, Isabelle Schuffenecker, Sonia Burel, Jérome Kaplon, Stéphanie Nguyen Quoc, Madalina Uzunov, Laetitia Souchet, Alexis de Rougemont, Damien Roos-Weil, and Marine Baron
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2023
9. Supplementary Figure 3 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Waffle chart (%) of patients addressed for cytopenia exploration after OC exposed to a PARPi treatment from cytopenia diagnosis (A) and cytopenia diagnosis based on NGS results (B). Dot plots (C) showing the median WBC, hemoglobin, and platelet counts from patients referred for cytopenia exploration after OC exposed to a PARPi treatment according to t-MN diagnosis (“t-MN”) or not (“Cytopenia”).
- Published
- 2023
10. Supplementary Figure 2 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Blood smear and bone marrow aspiration of patient referred for cytopenia post PARPi.
- Published
- 2023
11. Supplementary Figure 4 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Commutation plot visualizing the mutated genes in t-MN after OC according to PARPi treatment.
- Published
- 2023
12. Supplementary Table 3 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Univariate analysis for overall survival from t-MN diagnosis of patients from the national cohort.
- Published
- 2023
13. Supplementary Figure 1 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Flow chart of the study displaying the three cohorts.
- Published
- 2023
14. Supplementary Table 2 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
TP53 mutations characteristics among t-MN PARPi national cohort.
- Published
- 2023
15. Supplementary Table 1 from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Univariate analysis for overall survival from t-MN diagnosis of patients diagnosed with t-MN after OC according to PARPi exposure.
- Published
- 2023
16. Data from Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Jean-Baptiste Micol, Alexandra Leary, Christophe Marzac, Arnaud Pagès, Hervé Dombret, Christian Récher, Pierre Fenaux, Lionel Adès, Mauricette Michallet, Pierre-Marie Morice, Matthieu Duchmann, Pascal Bourquard, Marie-Pierre Gourin, Sylvain Thepot, Thomas Boyer, Marion Lepelley, Laetitia Stefani, Myrtille Thomas, Nathalie Auger, Véronique Vergé, Patricia Pautier, Félix Blanc-Durand, Nadine Morineau, Marion Loirat, Jérémy Delage, Emmanuelle Tavernier, Emilie Lemasle, Géraldine Salmeron, Jacques Vargaftig, Pierre-Yves Dumas, Edmond Chiche, Céline Berthon, Alexis Genthon, Madalina Uzunov, Sylvain Chantepie, Célestine Simand, Lauris Gastaud, Sarah Bertoli, Amine Belhabri, Gabriel Etienne, Sylvain Garciaz, Justine Decroocq, and Vincent Marmouset
- Abstract
Purpose:To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi).Experimental Design:In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort.Results:From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4–14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS.Conclusions:In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.
- Published
- 2023
17. CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network
- Author
-
Marion Alcantara, Caroline Houillier, Marie Blonski, Marie-Thérèse Rubio, Lise Willems, Agathe Waultier Rascalou, Magali Le Garff-Tavernier, Karim Maloum, Clotilde Bravetti, Laetitia Souchet, Damien Roos-Weil, Véronique Morel, Madalina Uzunov, Carole Metz, Meriem Dhib-Charfi, Stéphanie Nguyen, Natalia Shor, Dimitri Psimaras, Nicolas Weiss, Nathalie Jacque, Silvia Solorzano, Nicolas Gauthier, Marie Le Cann, Françoise Norol, Carole Soussain, and Sylvain Choquet
- Subjects
Central Nervous System ,Male ,Immunology ,Cell Biology ,Hematology ,Middle Aged ,Immunotherapy, Adoptive ,Survival Analysis ,Biochemistry ,Central Nervous System Neoplasms ,Cohort Studies ,Humans ,Female ,France ,Lymphoma, Large B-Cell, Diffuse ,Letter to Blood ,Aged - Published
- 2022
18. Gilteritinib activity in refractory or relapsed FLT3-mutated acute myeloid leukemia patients previously treated by intensive chemotherapy and midostaurin: a study from the French AML Intergroup ALFA/FILO
- Author
-
Pierre-Yves Dumas, Emmanuel Raffoux, Emilie Bérard, Sarah Bertoli, Marie-Anne Hospital, Maël Heiblig, Yohann Desbrosses, Caroline Bonmati, Cécile Pautas, Juliette Lambert, Corentin Orvain, Anne Banos, Florence Pasquier, Pierre Peterlin, Tony Marchand, Madalina Uzunov, Jamilé Frayfer, Pascal Turlure, Thomas Cluzeau, Eric Jourdan, Chantal Himberlin, Emmanuelle Tavernier, Alban Villate, Stephanie Haiat, Marie-Lorraine Chretien, Martin Carre, Sylvain Chantepie, Ioana Vaida, Mathieu Wemeau, Safia Chebrek, Gaelle Guillerm, Romain Guièze, Houria Debarri, Eve Gehlkopf, Kamel Laribi, Ambroise Marcais, Alberto Santagostino, Marie-Christine Béné, Ariane Mineur, Arnaud Pigneux, Hervé Dombret, and Christian Récher
- Subjects
Cancer Research ,Oncology ,Hematology - Abstract
The real-world efficacy and safety of gilteritinib was assessed in an ambispective study that included 167 R/R FLT3-mutated AML patients. Among them, 140 received gilteritinib as single agent (cohort B), including 67 previously treated by intensive chemotherapy and midostaurin (cohort C). The main differences in patient characteristics in this study compared to the ADMIRAL trial were ECOG ≥ 2 (83.6% vs. 16.6%), FLT3-TKD mutation (21.0% vs. 8.5%), primary induction failure (15.0% vs. 40.0%) and line of treatment (beyond 2nd in 37.1% vs. 0.0%). The rates of composite complete remission, excluding those that occurred after hematopoietic stem cell transplantation (HSCT), were similar at respectively 25.4% and 27.5% in cohorts B and C. Median overall survival (OS) for these two groups was also similar at respectively 6.4 and 7.8 months. Multivariate analyses for prognostic factors associated with OS identified female gender (HR 1.61), adverse cytogenetic risk (HR 2.52), and allogenic HSCT after gilteritinib (HR 0.13). Although these patients were more heavily pretreated, these real-world data reproduce the results of ADMIRAL and provide new insights into the course of patients previously treated by intensive chemotherapy and midostaurin and beyond the 2nd line of treatment who can benefit from treatment in an outpatient setting.
- Published
- 2022
19. Therapy-related Myeloid Neoplasms Following PARP Inhibitors: Real-life Experience
- Author
-
Vincent Marmouset, Justine Decroocq, Sylvain Garciaz, Gabriel Etienne, Amine Belhabri, Sarah Bertoli, Lauris Gastaud, Celestine Simand, Sylvain Chantepie, Madalina Uzunov, Alexis Genthon, Celine Berthon, Edmond Chiche, Pierre-Yves Dumas, Jacques Vargaftig, Géraldine Salmeron, Emilie Lemasle, Emmanuelle Tavernier, Jeremy Delage, Marion Loirat, Nadine Morineau, Felix Blanc-Durand, Patricia Pautier, Veronique Vergé, Nathalie Auger, Myrtille Thomas, Laetitia Stefani, Marion Lepelley, Thomas Boyer, Sylvain Thepot, Marie-Pierre Gourin, Pascal Bourquard, Matthieu Duchmann, Pierre Morice, Mauricette Michallet, Lionel Ades, Pierre Fenaux, Christian Recher, Hervé Dombret, Arnaud Pages, Christophe Marzac, Alexandra Leary, Jean-Baptiste Micol, Université de Picardie Jules Verne (UPJV), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Aix Marseille Université (AMU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Bergonié [Bordeaux], UNICANCER, Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], CHU Lille, Université Côte d'Azur - Faculté de Médecine (UCA Faculté Médecine), Université Côte d'Azur (UCA), BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique et Thérapie Cellulaire [CHU Bordeaux], Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CH de Saint-Nazaire, CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Ovarian Neoplasms ,Cancer Research ,Immunology ,Neoplasms, Second Primary ,Cell Biology ,Hematology ,Poly(ADP-ribose) Polymerase Inhibitors ,Carcinoma, Ovarian Epithelial ,Biochemistry ,Oncology ,Mutation ,Humans ,Female ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Germ-Line Mutation - Abstract
Purpose: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). Experimental Design: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. Results: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4–14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. Conclusions: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.
- Published
- 2022
20. Minimal residual disease quantification in ovarian tissue collected from patients in complete remission of acute leukemia
- Author
-
Chrystelle Abdo, Jean-Michel Cayuela, Hervé Dombret, Nathalie Dhedin, Florian Chevillon, Catherine Poirot, Emmanuelle Clappier, Régis Peffault de Latour, Véronique Meignin, Madalina Uzunov, Jean Hugues Dalle, Aurélie Caye-Eude, Michaël Degaud, Céline Chalas, Marion Alcantara, Nicolas Boissel, Chloé Arfeuille, Véronique Drouineaud, and Rathana Kim
- Subjects
Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Neoplasm, Residual ,Immunology ,MEDLINE ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Internal medicine ,Humans ,Medicine ,Acute leukemia ,business.industry ,Ovarian tissue ,Ovary ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Complete remission ,Organ Preservation ,Cell Biology ,Hematology ,Minimal residual disease ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Female ,business ,030215 immunology - Published
- 2021
21. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard?
- Author
-
Amélie Guihot, Madalina Uzunov, Sophie Demeret, Agnès Bellanger, David Saadoun, Damien Roos-Weil, Claire Deback, Valérie Pourcher, Ahmed Idbaih, Nicolas Weiss, Natalia Shor, Veronique Leblond, Damien Galanaud, Caroline Houillier, Bruno Eymard, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
- Subjects
Oncology ,medicine.medical_specialty ,Neurology ,business.industry ,medicine.drug_class ,Progressive multifocal leukoencephalopathy ,medicine.medical_treatment ,Immunosuppression ,Context (language use) ,medicine.disease ,Monoclonal antibody ,Myasthenia gravis ,Immune system ,Internal medicine ,medicine ,Neurology (clinical) ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Encephalitis - Abstract
Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML. We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14–33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML. Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
- Published
- 2021
22. Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study
- Author
-
Claude Preudhomme, Cyril Quivoron, Sophie Broutin, Emmanuelle Clappier, Aline Renneville, S. de Botton, Christophe Willekens, Angelo Paci, Ramy Rahmé, Julien Rossignol, Pierre Fenaux, Laurence Simon, Raphael Itzykson, Alice Marceau, Eyal C. Attar, Véronique Saada, Mark G. Frattini, Jean-Baptiste Micol, Madalina Uzunov, Florence Pasquier, Laurent Pascal, Thorsten Braun, Emmanuel Raffoux, Matthieu Duchmann, Julia Delahousse, V. Vidal, Virginie Penard-Lacronique, and Lionel Adès
- Subjects
Cancer Research ,Myeloid ,IDH1 ,business.industry ,Myelodysplastic syndromes ,Azacitidine ,Myeloid leukemia ,Hematology ,medicine.disease ,IDH2 ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Isocitrate dehydrogenase ,Oncology ,Multicenter study ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,business ,030215 immunology ,medicine.drug - Abstract
Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) re...
- Published
- 2020
23. Ponatinib-based therapy in adults with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the real-life OPAL study
- Author
-
Suzanne Tavitian, Yosr Hicheri, Xavier Thomas, Madalina Uzunov, Maria Pilar Gallego Hernanz, Véronique Lhéritier, Hervé Dombret, Patrice Chevallier, Ana Berceanu, Emilie Bérard, Thibaut Leguay, Didier Bouscary, Françoise Huguet, Emmanuel Raffoux, Stéphane Leprêtre, and Sarah Bertoli
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lymphoblastic Leukemia ,Philadelphia chromosome ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,Retrospective analysis ,Humans ,Medicine ,Philadelphia Chromosome ,Protein Kinase Inhibitors ,Retrospective Studies ,Philadelphia Chromosome Positive ,business.industry ,Ponatinib ,Imidazoles ,hemic and immune systems ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,humanities ,Pyridazines ,body regions ,chemistry ,030220 oncology & carcinogenesis ,business ,030215 immunology - Abstract
The OPAL study is a French multicenter observational retrospective analysis of adults with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia treated in a real-life setting by ponatinib. Twenty-nine patients were included since 2012. Median age was 55 years. The initial dose of ponatinib, combined to chemotherapy in half of the patients, was 45 mg/day in most instances. The remission rate was 90% and seven patients received allogeneic stem cell transplantation. Median disease-free and overall survival were only 3.5 and 9.9 months respectively. The outcome of patients with
- Published
- 2020
24. Therapy-related myeloid neoplasms following treatment with PARP inhibitors: new molecular insights
- Author
-
Sylvain Garciaz, Olivier Caron, Amine Belhabri, Norbert Vey, Jacques Vargaftig, Veronique Verge, Sophie Cotteret, S. de Botton, Flore Salviat, Suzette Delaloge, Iléana Antony-Debré, Patricia Pautier, Christophe Marzac, Sarah Bertoli, Florence Pasquier, Jean-Baptiste Micol, Sabine Khalife-Hachem, Alexandra Leary, Etienne Rouleau, A Renneville, M Kfoury, Filippo Rosselli, Thomas Grinda, Christian Recher, Madalina Uzunov, Jean-Edouard Martin, Gabriel Etienne, Institut Gustave Roussy (IGR), Université Paris-Saclay, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Curie [Paris], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Intégrité du génome et cancers (IGC), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], Oncologie gynécologique, Institut Bergonié [Bordeaux], UNICANCER, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), and NUNES, Jacques A
- Subjects
Myeloid ,DNA Repair ,Poly ADP ribose polymerase ,[SDV]Life Sciences [q-bio] ,MEDLINE ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Poly(ADP-ribose) Polymerase Inhibitors ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Neoplasms ,Humans ,Medicine ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Ovarian Neoplasms ,0303 health sciences ,Therapy related ,business.industry ,Hematology ,3. Good health ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Female ,Poly(ADP-ribose) Polymerases ,business - Abstract
International audience; No abstract available
- Published
- 2021
25. CAR‐T CELL THERAPY IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA (PCNSL): THE EXPERIENCE OF THE FRENCH NETWORK FOR OCULO‐CEREBRAL LYMPHOMAS (LOC)
- Author
-
M. Garff‐Tavernier, M. Alcantara, N. Gauthier, M. Blonski, A. Waultier Rascalou, R. Fior, S. N’guyen-Quoc, C. Metz, N. Jacque, M. Cann, Madalina Uzunov, Lise Willems, L. Souchet, Damien Roos-Weil, Véronique Morel, Caroline Houillier, Marie T Rubio, Sylvain Choquet, F. Norol, C. Salanoubat, and Carole Soussain
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Primary central nervous system lymphoma ,CAR T-cell therapy ,Medicine ,Hematology ,General Medicine ,business ,medicine.disease - Published
- 2021
26. USE OF METHOTREXATE, WHATEVER KIDNEY FUNCTION, WITH A SIMPLE ALGORITHM, RADICALLY CHANGES THE PROGNOSIS OF POST‐TRANSPLANT CNS LYMPHOMAS
- Author
-
Véronique Morel, Sylvain Choquet, Inès Boussen, Anne Lavaud, Damien Roos-Weil, Madalina Uzunov, S. Solorzano, M. Le Garff, and Veronique Leblond
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Renal function ,Hematology ,General Medicine ,Post transplant ,Internal medicine ,medicine ,Methotrexate ,business ,Cns lymphomas ,medicine.drug - Published
- 2021
27. Development and clinical validation of a simple and fast UPLC-ESI-MS/MS method for simultaneous quantification of nine kinase inhibitors and two antiandrogen drugs in human plasma: interest for their therapeutic drug monitoring
- Author
-
Fleur Cohen Aubart, Baptiste Abbar, Noël Zahr, Bruno Pinna, Nadine Tissot, Joe-Elie Salem, Christian Funck-Brentano, Damien roos Weil, Benoit Llopis, Paul Gougis, Madalina Uzunov, Luca Campedel, Pascal Robidou, Joseph Gligorov, Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut E3M [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
antiandrogens ,therapeutic drug monitoring ,Clinical Biochemistry ,Pharmaceutical Science ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Palbociclib ,01 natural sciences ,Analytical Chemistry ,oral targeted therapies ,chemistry.chemical_compound ,Pharmacokinetics ,Tandem Mass Spectrometry ,Drug Discovery ,medicine ,Humans ,liquid chromatography ,kinase inhibitors ,Protein Kinase Inhibitors ,Chromatography, High Pressure Liquid ,Spectroscopy ,Active metabolite ,mass spectrometry ,Cobimetinib ,Chromatography ,medicine.diagnostic_test ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Reproducibility of Results ,Androgen Antagonists ,0104 chemical sciences ,Dasatinib ,Pharmaceutical Preparations ,Nilotinib ,Therapeutic drug monitoring ,Pharmacodynamics ,Drug Monitoring ,Chromatography, Liquid ,medicine.drug - Abstract
International audience; Kinase inhibitors (KIs) and antiandrogen drugs (AAs) are oral anticancer drugs with narrow therapeutic index that exhibit high inter-and intra-individual variability. We describe here a UPLC-MS/MS method for the simultaneous quantification of nine KIs: cobimetinib, dasatinib, ibrutinib, imatinib, nilotinib, palbociclib, ruxolitinib, sorafenib and vemurafenib; two active metabolites of them: N-desmethyl imatinib, N-oxide sorafenib; and two AAs: abiraterone and enzalutamide; with short pre-treatment and run time in order to be easily used in clinical practice for their therapeutic drug monitoring (TDM) and facilitating pharmacokinetics and pharmacokinetics/pharmacodynamics studies. Plasma samples were prepared by a single-step protein precipitation. Analytes were separated on a Waters Acquity UPLC ® T3 HSS C18 column by non-linear gradient elution; with subsequent detection by Xevo ® TQD triple quadrupole tandem mass spectrometer in a positive ionization mode. Analysis time was 2.8 minutes per run, and all analytes eluted within 1.46-1.97 minutes. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, dilution integrity and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1-500 ng/mL for abiraterone, dasatinib and ibrutinib; 5-500 ng/mL for cobimetinib and palbociclib; 10-5,000 ng/mL for imatinib, N-desmethyl imatinib, nilotinib, sorafenib, N-oxide sorafenib and ruxolitinib; 100-50,000 ng/mL for enzalutamide and 100-100,000 ng/mL for vemurafenib with coefficient of correlation above 0.995 for all analytes. This novel method was successfully applied to TDM in clinical practice.
- Published
- 2021
28. Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard?
- Author
-
Damien, Roos-Weil, Nicolas, Weiss, Amélie, Guihot, Madalina, Uzunov, Agnès, Bellanger, Bruno, Eymard, David, Saadoun, Caroline, Houillier, Ahmed, Idbaih, Sophie, Demeret, Claire, Deback, Véronique, Leblond, Damien, Galanaud, Natalia, Shor, and Valérie, Pourcher
- Subjects
Antineoplastic Agents, Immunological ,Leukoencephalopathy, Progressive Multifocal ,Antibodies, Monoclonal ,Humans ,Immune Checkpoint Inhibitors ,JC Virus - Abstract
Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML.We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14-33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML.Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
- Published
- 2020
29. Postallogeneic transplantation progressive multifocal leukoencephalopathy successfully treated by nivolumab
- Author
-
Houria Chavez, Madalina Uzunov, Damien Roos-Weil, Stephanie Nguyen-Quoc, Jacques Gasnault, Veronique Leblond, Sophie Demeret, Véronique Morel, and Agnès Bellanger
- Subjects
Oncology ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,Immune checkpoint inhibitors ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,Hematology ,Middle Aged ,medicine.disease ,Leukoencephalopathy ,Transplantation ,Antineoplastic Agents, Immunological ,Nivolumab ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Female ,business - Published
- 2019
30. Prevention of Invasive Aspergillus Fungal Infections with the Suspension and Delayed-Release Tablet Formulations of Posaconazole in Patients with Haematologic Malignancies
- Author
-
Elisabeth Leclerc, Madalina Uzunov, Veronique Leblond, David Combarel, Christian Funck-Brentano, Noël Zahr, CIC Paris Est, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], HAL UPMC, Gestionnaire, Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
- Subjects
0301 basic medicine ,[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Male ,Posaconazole ,Antifungal Agents ,medicine.medical_treatment ,lcsh:Medicine ,Aspergillosis ,Gastroenterology ,Plasma ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,lcsh:Science ,Invasive Pulmonary Aspergillosis ,Multidisciplinary ,biology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,3. Good health ,Treatment Outcome ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Hematologic Neoplasms ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Female ,medicine.drug ,Tablets ,Adult ,medicine.medical_specialty ,030106 microbiology ,Chemoprevention ,Article ,03 medical and health sciences ,Delayed-release tablet ,Suspensions ,Internal medicine ,medicine ,Humans ,In patient ,Aged ,Aspergillus ,Chemotherapy ,business.industry ,lcsh:R ,Triazoles ,medicine.disease ,biology.organism_classification ,Bioavailability ,Transplantation ,Delayed-Action Preparations ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,lcsh:Q ,business - Abstract
Posaconazole is a triazole antifungal used to prevent invasive fungal infections (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell transplantation. Due to highly variable bioavailability of the oral suspension formulation, a delayed-release tablet was developed which showed improved bioavailability. A minimal target posaconazole plasma concentration of 0.7 mg/L is recommended for prophylaxis of IFIs. However, the relationship between plasma concentration of posaconazole and its efficacy against IFIs remains unclear. We analysed trough posaconazole concentrations and response against IFIs in 50 and 104 patients with haematologic malignancies receiving prophylactic posaconazole as the tablet or suspension formulation, respectively. Mean plasma concentration of posaconazole was 1.91 ± 1.06 mg/L and 0.82 ± 0.57 mg/L in the tablet and the oral suspension group, respectively (p p p = 0.032). Our results show a relationship between plasma concentrations of posaconazole and its prophylactic efficacy in patients with haematologic malignancies. Target posaconazole concentrations are reached more efficiently with the tablet than with the suspension formulation.
- Published
- 2018
31. Radical Improvement in Prognosis of CNS Ptlds Using Methotrexate Dose Alorithm Regardless of Renal Function
- Author
-
Veronique Leblond, Damien Roos-Weil, Silvia Solorzano, Madalina Uzunov, Véronique Morel, Anne Lavaud, Inès Boussen, and Sylvain Choquet
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Urology ,Medicine ,Renal function ,Methotrexate ,Cell Biology ,Hematology ,business ,Biochemistry ,medicine.drug - Abstract
Introduction While systemic post-transplant lymphoproliferations (PTLDs) have a good prognosis, with a median survival of more than 6 years, PTLD of the central nervous system (CNS-PTLD) have a very poor prognosis with a CR rate of 38% and overall survival (OS) of 43% at 3 years. The main prognostic criterion being the response to the first line (Evens AM et al. Am J Transpl 2013), we hypothesized that the majority of treatment failures were due to the absence or underuse of the major drug in CNS NHL treatment, namely methotrexate (Mtx), due to the high rate of renal failure in transplanted patients. Patients and methods Since April 2017, CNS-PTLD treated at Pitie-Salpetriere Hospital, Paris, France, have been systematically treated with a combination of methotrexate on day 1, Cytarabine on days 2 and 3, every 15 days for 6 cures. Cytarabine is given at 2g/m 2/d when the creatinine clearance (cc) is > 50ml/min, 1g/m 2/d below. The dose of Mtx of the first treatment is 100 mg/m 2 in case of dialysis or cc 65 years, 3000mg/m 2 in other cases. The dose of Mtx during the following treatments depends on the dosage of Mtx at 24h: below 1 microM the following dose is increased, above 5 microM it is reduced otherwise it remains the same. The results are compared to those of CNS-PTLDs treated in the same unit before April 2017 Results Of the 182 PTLDs treated since 1990 at Pitie-Salpetriere hospital, 49 are CNS-PTLD, including 16 processed with the new algorithm. The median age is 58 years, 9 patients have kidney or kidney-pancreas transplants, 2 heart, 1 lung and 3 liver, all are EBV positive diffuse large B cell CNS-PTLDs. The diagnosis is made in median 88 months after the transplantation. The cc at the diagnosis is in median of 50 ml / min. Of these 16 patients, only 2 had a cc> 60 ml/min, and only two were able to receive 3000 mg/m 2 of Mtx. The other patients received between 100 and 1000 mg/m 2 at the first treatment, 6 had an increased dose during the next cycles following the algorithm. No worsening of renal function or overdose of Mtx have been rated. Of the 16 patients 14 achieved complete remission (93%), 1 a PR, 1 died of progression after the first cycle, 1 relapsed within 3 months and 1 after 1 year of CR. Median overall survival (OS) is not achieved (448 days +). In comparison, of the 33 CNS-PTLDs treated before April 2017, 10 obtained a CR (30%), 6 a PR and the median OS is 211 days, for the 9 CNS-PTLDs treated without Mtx, only one obtained a CR, 1 a PR and their OS is only 180 days (p=0.016) cf figure Conclusion Contrary to general belief, methotrexate can be used regardless of the renal function by adapting its dose to the cc then to the dosages at H24. This new simple algorithm increased the CR rate from 30% to more than 90% and improve OS. In case of confirmation on further series, this new attitude should revolutionize the management of CNS-PTLDs ... but also other CNS-NHLs in case of renal failure Figure 1 Figure 1. Disclosures Leblond: AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Lilly: Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Roche: Honoraria; Amgen: Honoraria; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
- Published
- 2021
32. FLAMSA-Busulfan-Melphalan as a Sequential Conditioning Regimen in HLA-Matched or Haploidentical Hematopoietic Stem Cell Transplantation for High-Risk Myeloid Diseases
- Author
-
Inès Boussen, Adrien Grenier, Stéphanie Nguyen, Madalina Uzunov, Véronique Morel, Laetitia Souchet, Ludovic Jondreville, Damien Roos-Weil, and Françoise Norol
- Subjects
Oncology ,Melphalan ,medicine.medical_specialty ,Myeloid ,Cyclophosphamide ,medicine.medical_treatment ,Context (language use) ,Hematopoietic stem cell transplantation ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Busulfan ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Fludarabine ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,medicine.anatomical_structure ,Cytarabine ,Molecular Medicine ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential scheme combining fludarabine, amsacrine, and cytarabine (FLAMSA) for cytoreduction, followed by reduced-intensity conditioning with busulfan and melphalan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical HSCT. This single-center retrospective study included 36 adult patients with high-risk myeloid malignancies who underwent allo-HSCT from HLA-matched (n = 19) or haploidentical (n = 17) donors. Along with the standard prophylaxis for graft-versus-host disease (GVHD), patients with a haploidentical donor received post-transplantation high-dose cyclophosphamide. A post-transplantation consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was provided whenever possible. Thirty patients (83%) achieved complete remission on day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group versus 34% in the haploidentical group (P = .0018). The 2-year disease-free survival in these 2 groups was 68% and 34%, respectively (P = .013). At 2 years, the probability of relapse was 32% and 20%, respectively, and nonrelapse mortality was 0% and 58%, respectively (P = .0003). The leading cause of death was relapse in the HLA-matched group (3 of 19) and hemorrhagic events (5 of 17) in the haploidentical group, favored by significantly delayed platelet reconstitution and a severe GVHD context. These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning in allo-HSCT for high-risk myeloid malignancies. The use of bone marrow as the preferred graft source might reduce the incidence of acute GVHD and nonrelapse mortality in the haploidentical transplantation setting.
- Published
- 2021
33. Therapy Related Myeloid Neoplasm Post PARP Inhibitors: Potential Clonal Selection
- Author
-
Madalina Uzunov, Sarah Bertoli, Amine Belhabri, Iléana Antony-Debré, Véronique Saada, Nathalie Auger, Thomas Grinda, Sabine Khalife-Hachem, Olivier Caron, Alexandra Leary, Maria Kfoury, Christel Guillouf, Florence Pasquier, Filippo Rosselli, Stéphane de Botton, Sylvain Garciaz, Gabriel Etienne, Etienne Rouleau, Jacques Vargaftig, Patricia Pautier, Christophe Marzac, Jean-Baptiste Micol, Norbert Vey, Jean-Edouard Martin, and Flore Salviat
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,Myeloid ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Gene mutation ,Biochemistry ,Olaparib ,Targeted therapy ,Radiation therapy ,chemistry.chemical_compound ,medicine.anatomical_structure ,Germline mutation ,chemistry ,Internal medicine ,medicine ,Rucaparib ,business - Abstract
Introduction Clonal selection is one of the mechanisms leading to therapy-related myeloid neoplasms (TRMN). A preexisting somatic mutation in hematopoietic stem cell (defined as clonal hematopoiesis [CH]) emerges under pressure of chemotherapy or radiotherapy, leading to TRMN development. Most of these mutations belong to the DNA damage response (DDR) pathway as TP53 or PPM1D mutations and are known to confer a dismal prognosis. Recently authorized for the treatment of ovarian cancers (OC), the poly (ADP-ribose) polymerase inhibitors (PARPi) represent a promising targeted therapy. However, by inducing DNA damage and altering DNA repair process, PARP inhibition could represent a challenge for the genetic stability of the healthy tissues. Thus, we assessed the effect of PARP inhibition on the development of CH and TRMN after PARPi treatment for OC (TRMN-PARPi) in combination with chemotherapies. Methods Firstly, we performed a targeted 77 genes mutational analysis using Next Generation Sequencing (NGS) in 13 patients exposed to PARPi without TRMN. Secondly, we retrospectively identified, with the help of the UNIHEM group of Unicancer, 17 patients who experienced TRMN-PARPi. Clinical, biological and survival data were collected and compared to 23 OC patients with TRMN not treated with PARPi (Gustave Roussy institutional database). Lastly, NGS was performed for 3 patients with TRMN-PARPi with sequential sampling. Patient's samples were obtained with informed consent. Results Thirteen OC patients during maintenance treatment with PARPi without TRMN were explored by NGS. Median age at NGS was 64.5 years old (yo) (40.5-75.3). 4/13 (31%) patients harbored BRCA1/2 germline mutation. Time between OC diagnosis and NGS was 4.3 y (1-11.6). The median number of chemotherapy line at PARPi initiation was 2 (1-3). 7 received Olaparib, 5 Niraparib and 1 Rucaparib. The median duration of PARPi treatment before NGS was 4.7 months (1.1-25.1). 12/13 patients experienced hematological toxicities during the PARPi treatment. CH was found in 10/13 (77%) patients (Figure 1a), including mutations of DDR genes in 8/10 (80%). 6/8 (75%) patients had 2 or more gene mutations. Next we identified 17 cases of TRMN occurring during or after PARPi administration for OC (6/17 [35%] t-AML and 11/17 [65%] t-MDS). 12/17 (71%) patients had BRCA germline mutations (7 BRCA1 and 5 BRCA2). All received Olaparib with a median dose of 600mg/d (400-1200). Median duration of Olaparib treatment was 1.7 years (0.2-4.6). TRMN-PARPi were described 1.4 months (0-10.9) after the end of PARPi administration. We compared these patients to a cohort of TRMN post OC not treated by PARPi. Number of therapy lines for OC, time between TRMN and OC diagnosis, median age at TRMN, were, for TRMN-PARPi, 2 (1-8), 5.9 y (0.9-20.8), 64.4 yo (46-74); respectively, compared to 3 (1-8), 4.9 y (1.7-36.9), 59.3 yo (35.7-85.7); (p=ns). TRMN-PARPi cytogenetic was unfavorable for 16/17 (94%) (including 11/17 [65%] complex karyotype) compared to 16/23 (70%) (11/23 [48%] complex karyotype). C Median survival was significantly lower in the TRMN-PARPi group 3.9 months 95%CI [2.0-9.7] and 6.1 months 95%CI [4.1-15.8] respectively, p=0.046, Fig 1b). However, median survival from OC diagnosis was not different between the two groups 6.2 y 95%CI [5.6-NA] for TRMN-PARPi vs 5.6 y 95%CI [5.0-11.6]. NGS was available for 8/17 TRMN-PARPi and revealed mutations in DDR genes in 7/8 patients (6 patients with TP53 mutation, 2 with PPM1D mutation). For 3 patients, we had samples from OC stage, before PARPi administration. We found that mutations from TRMN stage were present at lower frequency, confirming clonal selection by PARPi treatment (Figure 1c). Conclusions Here we described, for the first time, a cohort of TRMN patients previously treated with PARPi for an OC. Intriguingly, most of these TRMN occurred with a short latency at the end of PARPi treatment, with unfavorable cytogenetic and very short OS. Moreover, we found a very high percentage of CH involved in the DDR pathway (62%) in patients under PARPi treatment without TRMN suggesting a potential clonal selection which could lead ultimately to TRMN. PARPi are now indicated in 1rst line high grade OC regardless of BRCA status, which should expand indications. Benefit for OC patients is not questionable; however, caution will be warranted for patients with CH before PARPi treatment, especially implicating DDR mutations. Disclosures Etienne: Incyte: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.
- Published
- 2020
34. Myeloid Blast Crisis of Philadelphia Positive Chronic Myeloid Leukemia and Philadelphia Positive Acute Myeloid Leukemia Treated at the AP-HP in Paris: A Retrospective Analysis
- Author
-
Etienne Lengliné, Emmanuel Raffoux, Didier Bouscary, Matteo Dragani, Nicolas Boissel, Raphael Itzykson, Philippe Rousselot, Madalina Uzunov, Jean Michel Cayuela, Rathana Kim, Hervé Dombret, Felipe Suarez, Delphine Rea, and Clémence Loiseau
- Subjects
Oncology ,medicine.medical_specialty ,Performance status ,business.industry ,Immunology ,Ponatinib ,Imatinib ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Dasatinib ,chemistry.chemical_compound ,chemistry ,Nilotinib ,Median follow-up ,Internal medicine ,medicine ,Cytarabine ,business ,Progressive disease ,medicine.drug - Abstract
Introduction :Since the introduction of tyrosine kinase inhibitors (TKIs) the prognosis of Philadelphia positive (Ph+) diseases like chronic myeloid leukemia (CML) dramatically improved (Sasaki K, Lancet Haematol 2015). Nonetheless, myeloid blastic crisis of CML (MBC-CML) and Ph+ acute myeloid leukemia (AML) represent a clinical challenge due to their rarity, the absence of a standard therapy and mutations. Methods :We collected clinical data of patients treated in Paris in 5 different hospitals with confirmed diagnosis in patients with CML successively transformed in MBC-CML, and in patients with MBC-CML straight away or Ph+ AML. We performed descriptive analysis as well as analysis on overall survival (OS) and event-free survival (EFS). Results :We found 64 patients (24 F/40 M) treated since 2001 to present days. 35/64 patients had an history of CML before MBC of which 30 were diagnosed in chronic phase (Sokal risk: low 3 pts, intermediate 8 pts, high 4 pts, NA 15 pts) and 5 in accelerated phase according to ELN classification. Lines of treatment before MBC for these 35 patients were principally TKIs, IFN, hydroxyurea and homoarringtonine: 11 pts experienced only 1 line of treatment, 15 pts 2 lines, 5 pts 3 lines, 1 pt 4 lines and 3 pts 5 lines. Best response before MBC was complete hematological remission (CHR) for 14 pts, complete cytogenetic remission (CCyR) for 7 pts, molecular remission for 6 pts (4 pts MR3, 1 pt MR4, 1 pt CMR TKI free), whereas 8 pts never gained any response. 21/64 pts were in MBC at diagnosis and 8/64 pts were classified as Ph+ AML. At diagnosis of MBC/AML median age was 49 years old (11-73). 12/64 pts had an extramedullary/central nervous system (CNS) involvement of which 2 pts presented a solitary CNS disease and 3 patients had lesions compatible with myeloid sarcomas without marrow blasts. 46/64 pts (72%) received a classical induction therapy (mostly cytarabine + anthracycline combination) combined in 40 pts with a TKI (15 pts Imatinib, 13 pts Dasatinib, 2 Nilotinib and 10 Ponatinib). 11/64 pts (17%) started Azacytidine (1 pt in combination with Imatinib, 2 pts with Nilotinib, 6 pts with Dasatinib, 1 pt with Ponatinib and 1 pt with Venetoclax). 2/64 pts (3%) received Dasatinib monotherapy. 1/64 pt (2%) received ATRA+ATO+Dasatinib combination. 4/64 pts (6%) received only best supportive care. At first revaluation after therapy 47 pts (78%) were in CR/CRi, 9 pts (15%) were refractory, 2 pts (3%) died during induction, 1 pt (2%) induction therapy is ongoing, in 1 pt (2%) lost to follow up. Most patients who obtained CR/CRi after induction continued with consolidations, mostly high-dose Cytarabine associated with a TKI. 41 pts (68%) were transplanted (40 alloHSCT, 1 autoHSCT), 38 pts in first CR (CR1), 1 pt in second CR (CR2) and 2 pts in progressive disease. Notably, 1 pt who had only Dasatinib monotherapy without any form of chemotherapy nor allotransplant is still alive and in second chronic phase after more than two years of follow up. Median follow up for patients who received an active treatment was 23 months. Median OS was 44 months and median EFS was 29 months (figure 1). The only factor whose impact was significant for both OS and EFS in our cohort was transplant (p At last follow up, 30 pts (47%) are still alive (29 in CR, 1 pt with active refractory disease), 30 pts (47%) died, 4 pts (6%) are lost to follow up. Causes of death were progression of disease for 18 pts, sepsis for 7 pts, GVHD for 3 pts, ischemic stroke for 1 pt, cardiovascular complications for 1 pt. Conclusion :We showed here a multicentric experience about an unselected cohort of patients with MBC CML and Ph+ AML who received different treatments according to age, comorbidities, performance status, TKI availability. Survival of this cohort was mostly linked to the possibility to achieve CR and to perform an allotransplant. Already published experiences showed a generical dismal prognosis with median OS which doesn't exceed 1-2 years (16 months, Deau B, Leukemia Research 2011 ; 12 months, Palandri F, Haematologica 2008 ; 6.4 months, Fruehauf S, Cancer 2007) whereas in our real life cohort median OS was longer. For fit and potentially « transplantable » patients, combination with classic chemotherapy plus a TKI seems reasonable and associated with good outcomes in terms of OS and EFS. Disclosures Rousselot: Incyte:Consultancy, Research Funding;Pfizer:Consultancy, Research Funding;Bristol-Myers Squibb:Consultancy;Novartis:Consultancy;Takeda:Consultancy.Itzykson:Jazz Pharmaceuticals:Honoraria, Membership on an entity's Board of Directors or advisory committees;Daiichi Sankyo:Honoraria;BMS (Celgene):Honoraria;Sanofi:Honoraria;Astellas:Honoraria;Oncoethix (now Merck):Research Funding;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Research Funding;Stemline:Membership on an entity's Board of Directors or advisory committees;Karyopharm:Membership on an entity's Board of Directors or advisory committees;Otsuka Pharma:Membership on an entity's Board of Directors or advisory committees;Amgen:Membership on an entity's Board of Directors or advisory committees;Abbvie:Honoraria.Cayuela:Incyte:Speakers Bureau;Novartis:Speakers Bureau.Rea:BMS:Membership on an entity's Board of Directors or advisory committees;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer:Honoraria, Membership on an entity's Board of Directors or advisory committees;Incyte:Honoraria, Membership on an entity's Board of Directors or advisory committees.
- Published
- 2020
35. Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1
- Author
-
Veronique Leblond, Elise Chapiro, Claude Lesty, Madalina Uzunov, N Bougacha, Santos A. Susin, Florence Nguyen-Khac, M-N Brunelle-Navas, A Cosson, M Le Garff-Tavernier, Y Landesman, P. Feugier, Laurent Sutton, Véronique Morel, Damien Roos-Weil, Boris Keren, Hélène Merle-Béral, H-A Cung, Frederik Damm, L Herbi, Karim Maloum, Julie Lejeune, Sylvain Choquet, Stéphane Leprêtre, Jérôme Lambert, Caroline Algrin, Clementine Gabillaud, and Frederic Davi
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Receptors, Cytoplasmic and Nuclear ,Apoptosis ,Drug resistance ,Karyopherins ,Biology ,Fusion gene ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Gene ,Regulation of gene expression ,Hematology ,Gene Expression Regulation, Leukemic ,Triazoles ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Haematopoiesis ,Leukemia ,Hydrazines ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,Chromosomes, Human, Pair 2 ,030220 oncology & carcinogenesis ,Cancer research - Abstract
Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1
- Published
- 2017
36. Acute mast cell leukemia: A rare but highly aggressive hematopoietic neoplasm
- Author
-
Michel Arock, Dominique Bories, Madalina Uzunov, Myrto Costopoulos, Frédéric Charlotte, and Karim Maloum
- Subjects
Histology ,Adolescent ,Gene Expression ,Leukemia, Mast-Cell ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Immunophenotyping ,Fatal Outcome ,Antigens, CD ,medicine ,Pneumonia, Bacterial ,Neoplasm ,Humans ,Mast Cells ,Anaphylaxis ,Heart Failure ,Respiratory Distress Syndrome ,business.industry ,Ceftriaxone ,General Medicine ,medicine.disease ,Mast cell leukemia ,Kit d816v ,Haematopoiesis ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Acute Disease ,Cancer research ,Female ,business ,030215 immunology - Published
- 2018
37. Decreased Nonrelapse Mortality after Unrelated Cord Blood Transplantation for Acute Myeloid Leukemia Using Reduced-Intensity Conditioning: A Prospective Phase II Multicenter Trial
- Author
-
Mauricette Michallet, Faezeh Legrand, Natacha Maillard, Jérôme Cornillon, Patrice Chevallier, Gérard Socié, Jacques-Olivier Bay, Bernard Rio, Noel Milpied, Sébastien Maury, Tabassome Simon, Sabine Furst, Sylvie Chevret, Karin Bilger, Agnes Buzyn, Laurence Clement, Eliane Gluckman, Stephane Vigouroux, Anne Huynh, Ibrahim Yakoub-Agha, Anne Sirvent, Sylvie Françoise, Vanderson Rocha, Patrice Ceballos, Annalisa Ruggeri, Claude Eric Bulabois, Madalina Uzunov, Stéphanie Nguyen, Geneviève Margueritte, Gérard Michel, and Charles Dauriac
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Gastroenterology ,Disease-Free Survival ,Risk Factors ,hemic and lymphatic diseases ,Multicenter trial ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Child ,Aged ,Umbilical cord blood transplantation ,Chemotherapy ,Transplantation ,Nonrelapse mortality ,Acute myeloid leukemia ,business.industry ,Myeloid leukemia ,Hematology ,Middle Aged ,Myeloablative Agonists ,Total body irradiation ,Allografts ,Fludarabine ,Surgery ,Survival Rate ,Reduced-intensity conditioning ,Leukemia, Myeloid, Acute ,Child, Preschool ,Female ,Cord Blood Stem Cell Transplantation ,Unrelated Donors ,business ,Vidarabine ,Whole-Body Irradiation ,medicine.drug - Abstract
A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m2). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 107/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (
- Published
- 2015
- Full Text
- View/download PDF
38. Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord
- Author
-
S. Vigouroux, L Souchet, Patrice Chevallier, Anne Sirvent, C-E. Bulabois, Faezeh Legrand, Laurence Clement, Jérôme Cornillon, S. Furst, Sébastien Maury, Vivien Béziat, J Lejeune, Bernard Rio, Sylvie Chevret, G Margueritte, Sylvie François, Karin Bilger, Vincent Vieillard, G. Michel, Madalina Uzunov, Gérard Socié, Marie-Cécile Michallet, Patrice Ceballos, V. Rocha, J.-O. Bay, N. Maillard, Charles Dauriac, I. Yakoub-Agha, Abla Achour, Anne Huynh, Stéphanie Nguyen, Institut des Matériaux Jean Rouxel (IMN), Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Semiconductor Photonics Research Group, Trinity College Dublin-Science Foundation Ireland-Enterprise Ireland-Higher Education Authority, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), STMicroelectronics, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Public Henri Tudor [Technoport] (CRP Henri Tudor), Centre de Recherche Public Henri-Tudor [Luxembourg] (CRP Henri-Tudor), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de sismologie (DS (UMR_7580)), Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Centre National de la Recherche Scientifique (CNRS), Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel Dieu, IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel Dieu, Université de Nantes (UN)-Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
- Subjects
Adult ,Male ,0301 basic medicine ,Transplantation Conditioning ,Myeloid ,Cord Blood Stem Cell Transplantation ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Multicenter trial ,Humans ,Medicine ,Prospective Studies ,Registries ,ComputingMilieux_MISCELLANEOUS ,Transplantation ,business.industry ,Myeloid leukemia ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Recovery of Function ,Hematology ,Middle Aged ,Allografts ,medicine.disease ,3. Good health ,Killer Cells, Natural ,Survival Rate ,Leukemia, Myeloid, Acute ,Leukemia ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Female ,business ,030215 immunology - Abstract
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.
- Published
- 2017
39. An unusual case of acute leukemia
- Author
-
Madalina Uzunov, Myrto Costopoulos, Catherine Settegrana, Amélie Trinquand, Laurence Simon, Ines Safra Zaghouani, Magali Le Garff-Tavernier, Marie Passet, Marine Armand, Elise Chapiro, Carole Fleury, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'Hématologie, CHU Strasbourg, Service d'hématologie biologique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie biologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
Adult ,Male ,030213 general clinical medicine ,Myeloid ,medicine.medical_treatment ,T-Lymphocytes ,Population ,Hematopoietic stem cell transplantation ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology ,hemic and lymphatic diseases ,Medicine ,Humans ,Myeloid Cells ,education ,Chemotherapy ,education.field_of_study ,Acute leukemia ,B-Lymphocytes ,Leukemia ,business.industry ,flow cytometry ,T-cell receptor ,acute lymphoblastic T-cell leukemia ,lymphoid clonality ,General Medicine ,Minimal residual disease ,mixed phenotype acute leukemia ,3. Good health ,Leukemia, Biphenotypic, Acute ,medicine.anatomical_structure ,Acute Disease ,cytology ,Cancer research ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoidBand lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation. DNA-based techniques analyzing B and T-cell clonality identified partial rearrangements in immunoglobulin and TCR genes, allowing the monitoring of minimal residual disease. This observation highlights the difficulty to classify some atypical cases of acute leukemias. It emphasizes on the complementarity of cytomorphology, immunophenotyping by flow cytometry and molecular techniques in order to promptly characterize and treat these leukemias.
- Published
- 2017
40. Home spirometry in bronchiolitis obliterans after allogeneic haematopoietic cell transplant
- Author
-
Clémence Loiseau, Raphael Itzykson, Emilie Catherinot, Jean-Paul Vernant, Marie Hélène Becquemin, Madalina Uzunov, Odile Randrianarivelo, Hélène Salvator, Nathalie Dhedin, Colas Tcherakian, Stéphanie Nguyen, Louis Jean Couderc, Laurent Sutton, François Lemonnier, Elisabeth Rivaud, and Philippe Devillier
- Subjects
Pulmonary and Respiratory Medicine ,Spirometry ,Adult ,Male ,medicine.medical_specialty ,MEDLINE ,Bronchiolitis obliterans ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,medicine ,Humans ,Intensive care medicine ,Bronchiolitis Obliterans ,medicine.diagnostic_test ,business.industry ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,humanities ,Respiratory Function Tests ,Haematopoiesis ,surgical procedures, operative ,030228 respiratory system ,Female ,business - Abstract
Long-term outcome of patients with BOS post HSCT with home spirometry is encouraging despite suboptimal adherence
- Published
- 2017
41. Sex chromosome loss may represent a disease-associated clonal population in chronic lymphocytic leukemia
- Author
-
Iléana Antony-Debré, Hong-Anh Cung, Sylvain Choquet, Nathalie Marchay, Frederic Davi, Aurore Grelier, Karim Maloum, Laurent Sutton, Madalina Uzunov, Véronique Leblond, Elise Chapiro, Christophe Parizot, Florence Nguyen-Khac, Claude Lesty, Stéphanie Mathis, Hélène Merle-Béral, and Zahia Azgui
- Subjects
Cancer Research ,medicine.diagnostic_test ,Chronic lymphocytic leukemia ,Clone (cell biology) ,Ficoll ,Aneuploidy ,Biology ,medicine.disease ,Peripheral blood mononuclear cell ,Molecular biology ,Flow cytometry ,Leukemia ,immune system diseases ,hemic and lymphatic diseases ,Immunology ,Genetics ,medicine ,Fluorescence in situ hybridization - Abstract
Whether sex chromosome loss (SCL) is an age-related phenomenon or a cytogenetic marker of hematological disease is unclear. To address this issue in chronic lymphocytic leukemia (CLL), we investigated 20 cases with X or Y chromosome loss detected by conventional cytogenetics (CC). The frequency of SCL was low in CLL (2.3%). It was the sole abnormality, as detected by CC, in 10/20 (50%) patients. Fluorescence in situ hybridization (FISH) analyses confirmed SCL in all patients tested, present in 5-88% of cells (median: 68%). Deletions of 13q were observed by FISH in 16/20 (80%) patients. Compared with CLL without SCL, SCL was significantly associated with 13q deletion, especially when bi-allelic (P = 0.04). Co-hybridization analyses showed that SCL could be a concomitant, primary or secondary change, or be present in an independent clone. FISH analyses were performed on blood sub-populations isolated by Ficoll or flow cytometry. Comparing mononuclear cells (including CLL cells) and polynuclear cells separated by Ficoll, a maximum of 2% of polynuclear cells were found with SCL, whereas mononuclear cells exhibited a significantly higher loss frequency (range: 6-87%) (P = 0.03). Comparing B-cells (including CLL cells) and T-cells sorted by flow cytometry, the proportion of B-CD19+ cells with SCL was significantly higher (range: 88-96%) than that observed in T-CD3+ cells (range: 2-6%) (P = 0.008). We conclude that SCL has to be considered as a clonal aberration in CLL that may participate in the oncogenic process.
- Published
- 2013
42. Améliorer la relation ville-hôpital pour garantir la qualité de la prise en charge transfusionnelle des patients allogreffés de cellules souches hématopoïétiques (CSH) : à propos d’un cas
- Author
-
Liliane Bodin-Gauvin, Xavier Chamillard, Sandrine Roy, Madalina Uzunov, Josée Delort, Myriam Oranger, Isabelle Herve, and Mélanie Houot
- Subjects
Biochemistry (medical) ,Clinical Biochemistry ,Hematology - Abstract
Pour tout patient allogreffes (AG) de CSH, les cartes de groupe anterieures a la greffe doivent etre detruites. Des consignes transfusionnelles (CT) transitoires post-AG portant sur la qualification des produits sanguins labiles (irradiation…) ainsi que sur leurs caracteristiques immunologiques respectant la compatibilite donneur-receveur (groupe ABO, phenotype RH-KEL1) sont alors etablies. Un exemplaire est remis systematiquement au patient en sortie d’hospitalisation au cours d’une seance d’education therapeutique par le service d’hematologie de notre hopital. Nous rapportons ici un incident grave de la chaine transfusionnelle (IG) a propos d’un patient AG, Mr X, pris en charge dans un autre etablissement et pour lequel les CT etaient toujours maintenues (irradiation). En vue d’une cure chirurgicale pour hernie, un bilan preoperatoire comportant un groupage sanguin est prescrit a Mr X. Lors de la realisation de ce bilan en laboratoire de ville, bien que Mr X ait precise qu’il avait ete AG et possedait une carte post-AG, les 2 prelevements pour groupage sont realises considerant que sa carte post-AG n’est plus valide. Une carte de groupe « standard » lui est donc remise sans CT. Preoccupe par cette carte, Mr X contacte son medecin hematologue. Ce dernier informe immediatement le laboratoire de son erreur et previent le chirurgien allant prendre en charge Mr X. La nouvelle carte de groupe est finalement detruite. A la suite de ce signalement une declaration d’IG a ete faite. Une enquete avec analyse systemique a ete realisee au sein du laboratoire et a mene a la mise en place de plusieurs actions, notamment une sensibilisation du personnel a ces cas particuliers. Cet incident, non isole, montre a quel point l’education therapeutique du patient AG a toute son importance placant ce dernier comme acteur de sa prise en charge notamment lors des relais ville/hopital. Celui-ci etant au premier plan dans la transmission des informations concernant ces antecedent medicaux.
- Published
- 2018
43. Graft-versus-T-cell lymphoma effect: a sustained CR after tapering immunosuppressive drugs in a patient with angioimmunoblastic T-cell lymphoma in relapse after allogeneic transplantation
- Author
-
Madalina Uzunov, A L Brun, Caroline Algrin, Damien Roos-Weil, Veronique Leblond, A C Mamez, L Souchet, and Stéphanie Nguyen
- Subjects
Transplantation ,medicine.medical_specialty ,Angioimmunoblastic T-cell lymphoma ,Allogeneic transplantation ,business.industry ,T cell ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Gastroenterology ,Lymphoma ,surgical procedures, operative ,medicine.anatomical_structure ,Graft-versus-host disease ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Immunology ,medicine ,T-cell lymphoma ,business - Abstract
Graft-versus-T-cell lymphoma effect: a sustained CR after tapering immunosuppressive drugs in a patient with angioimmunoblastic T-cell lymphoma in relapse after allogeneic transplantation
- Published
- 2014
44. Lenalidomide as salvage treatment for multiple myeloma relapsing after allogeneic hematopoietic stem cell transplantation: a report from the French Society of Bone Marrow and Cellular Therapy
- Author
-
Olivier Hermine, Ibrahim Yakoub-Agha, Bruno Lioure, Tereza Coman, Stephane Vigouroux, Sébastien Maury, Simona Lapusan, Gérard Socié, Noel Milpied, Anne Huynh, A. Brebion, Madalina Uzunov, Sylvie François, Mauricette Michallet, Jean Bourhis, Mohamad Mohty, Marie-Thérèse Rubio, and Emmanuel Bachy
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Salvage therapy ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Cell therapy ,Transplantation ,Internal medicine ,Immunology ,medicine ,Progression-free survival ,Original Articles and Brief Reports ,business ,Dexamethasone ,Multiple myeloma ,medicine.drug ,Lenalidomide - Abstract
Optimal salvage treatment for multiple myeloma relapsing after allogeneic stem cell transplantation remains to be determined. Usually, such patients have been heavily pre-treated and present at relapse with a relatively refractory disease. Immunomodulatory properties of lenalidomide may be beneficial by facilitating a graft-versus-myeloma effect after allogeneic stem cell transplantation. However, the safety of such treatment is still under debate. We conducted a multicenter retrospective study and included 52 myeloma patients receiving lenalidomide alone or in combination with dexamethasone as salvage therapy after allogeneic stem cell transplantation. The first aim was to assess the efficacy and tolerance of this drug. The second aim was to evaluate its potential immunomodulatory effects evaluated on the occurrence of acute graft-versus-host disease under treatment. In this cohort, we show that lenalidomide can induce a high response rate of 83% (including 29% complete response). On lenalidomide therapy, 16 patients (31%) developed or exacerbated an acute graft-versus-host disease, which was the only factor significantly associated with an improved anti-myeloma response. Side effects were mostly reversible, whereas 2 deaths (4%) could be attributed to treatment toxicity and to graft-versus-host disease, respectively. With a median follow up of 16.3 months, the median overall and progression free survival were 30.5 and 18 months, respectively, independently of the occurrence of acute graft-versus-host disease under lenalidomide. Lenalidomide can induce high response rates in myeloma relapsing after allogeneic stem cell transplantation at least in part by triggering an allogeneic anti-myeloma response. Induced graft-versus-host disease has to be balanced against the potential benefit in terms of disease control. Further immunological studies would help us understand lenalidomide immunomodulatory activity in vivo.
- Published
- 2012
45. Calcineurin inhibitors impair neutrophil activity against Aspergillus fumigatus in allogenic hematopoietic stem cell transplant recipients
- Author
-
Priscillia Bresler, Sébastien Imbert, Alexandre Boissonnas, Madalina Uzunov, Stéphanie Nguyen, Laetitia Souchet, Lauraine Gauthier, Dominique Mazier, Veronique Leblond, Arnaud Fekkar, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
0301 basic medicine ,Hyphal growth ,Adult ,Male ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Neutrophils ,medicine.medical_treatment ,Immunology ,Calcineurin Inhibitors ,chemical and pharmacologic phenomena ,Video microscopy ,Hematopoietic stem cell transplantation ,Neutropenia ,Aspergillus fumigatus ,03 medical and health sciences ,Young Adult ,Invasive fungal infection ,immune system diseases ,Calcineurin inhibitor ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,hemic and lymphatic diseases ,medicine ,Immunology and Allergy ,Humans ,Aged ,Innate immunity ,Transplantation ,biology ,Hematopoietic Stem Cell Transplantation ,Neutrophil extracellular traps ,Middle Aged ,Immune reconstitution ,biology.organism_classification ,medicine.disease ,3. Good health ,Calcineurin ,030104 developmental biology ,surgical procedures, operative ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Reactive Oxygen Species - Abstract
Background Neutrophils are key effectors against the widely distributed mold Aspergillus fumigatus , which is a major threat for immunocompromised patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients. Yet little is known about neutrophil activity over time after cell transplantation, especially regarding A fumigatus . Objective We aimed at assessing the activity of neutrophils on A fumigatus in allogeneic HSCT recipients at different posttransplantation time points. Methods We performed a longitudinal study involving 37 patients undergoing HSCT, drawing blood samples at engraftment and at 2, 6, and 10 months after the HSCT. Posttransplantation neutrophil activity in the recipients was compared with that of the respective donors. Neutrophil/ A fumigatus coculture, flow cytometry, and video microscopy were used to assess neutrophil inhibition of fungal growth, cell/fungus interactions, reactive oxygen species production, major surface molecule expression, and neutrophil extracellular trap (NET) formation. Results The ability of neutrophils to interfere with Aspergillus species hyphal growth was impaired after HSCT. The administration of calcineurin inhibitors appeared to play an important role in this impairment. We also observed that post-HSCT neutrophils produced less NETs, which was correlated with increased fungal growth. Tapering immunosuppression led to the recuperation of inhibition capacity 10 months after HSCT. Conclusion In HSCT recipients neutrophil-driven innate immunity to fungi is altered in the early posttransplantation period (between recovery from neutropenia and up to 6 months). This alteration is at least partly related to administration of calcineurin inhibitors and diminution of NETs production.
- Published
- 2016
46. Breakthrough invasive mould infections in patients treated with caspofungin
- Author
-
Cendrine Godet, Julie Scholler, Catherine Kauffmann-Lacroix, A. Elsendoorn, Annick Datry, Raoul Herbrecht, Madalina Uzunov, Valérie Letscher-Bru, Laurent Massias, Arnaud Fekkar, Yasmine Nivoix, and Katy-Anna Phai Pang
- Subjects
Adult ,Male ,Microbiology (medical) ,Fusariosis ,medicine.medical_specialty ,Antifungal Agents ,Cirrhosis ,Drug resistance ,Biology ,Aspergillosis ,Hospitals, University ,Mannans ,Echinocandins ,Lipopeptides ,Galactomannan ,chemistry.chemical_compound ,Caspofungin ,Drug Resistance, Fungal ,Internal medicine ,medicine ,Humans ,Mucormycosis ,skin and connective tissue diseases ,Aged ,medicine.diagnostic_test ,Hematopoietic Stem Cell Transplantation ,Galactose ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Surgery ,Infectious Diseases ,Bronchoalveolar lavage ,chemistry ,Hematologic Neoplasms ,Female ,France ,Pulmonary Aspergillosis - Abstract
Summary Objectives To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin. Methods Retrospective, non-interventional study conducted in three University Hospitals. Results Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis ( n = 3), empirical therapy ( n = 9) or directed therapy for candidemia ( n = 5) or aspergillosis ( n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis. Conclusions Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin.
- Published
- 2012
47. Infusion of allogeneic natural killer cells in a patient with acute myeloid leukemia in relapse after haploidentical hematopoietic stem cell transplantation
- Author
-
Dominique Bories, Madalina Uzunov, Françoise Norol, Patrice Debré, Helene Trebeden-Negre, Vivien Béziat, Jean-Paul Vernant, Nathalie Dhedin, Stéphanie Nguyen, Vincent Vieillard, Nabih Azar, and Ali Boudifa
- Subjects
Adult ,Male ,Myeloid ,medicine.medical_treatment ,Immunology ,Hematopoietic stem cell transplantation ,Immunotherapy, Adoptive ,KIR2DL1 ,Recurrence ,medicine ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,business.industry ,Histocompatibility Testing ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Immunotherapy ,medicine.disease ,Killer Cells, Natural ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,K562 Cells ,business ,K562 cells - Abstract
BACKGROUND: Allogeneic donor natural killer (NK)-cell infusion (NK-DLI) is a promising immunotherapy for patients with hematologic disorders. CASE REPORT: This report describes the case of a patient who received a single haploidentical NK-DLI for a relapse of acute myeloid leukemia (AML) after haploidentical hematopoietic stem cell transplantation. He underwent a cytoreductive, immunosuppressive regimen before NK-DLI and received high-dose interleukin-2 in vivo for 8 weeks afterward. RESULTS: No major adverse effect was observed. Prospective phenotypic and functional studies of the NK cells showed major expansion of infused NK cells and, more importantly, of the alloreactive KIR2DL1+KIR2DL2/DL3–NKG2A– subset, which reached 117 × 106 cells/L on Day +14 after NK-DLI, the greatest expansion of infused alloreactive NK cells reported so far. Infused NK cells conserved their lytic capacities against K562 target cells and primary AML-mismatched blasts. CONCLUSION: We review the literature to clarify these data and to detail the indications for allogeneic NK-DLI, the criteria for determining the most suitable donor, the types of conditioning regimens, and the procedures for selecting and activating NK cells.
- Published
- 2011
48. Regulatory T Cell Content in the Bone Marrow Graft Does Not Predict the Occurrence of Acute GVHD
- Author
-
Sébastien Maury, Gilbert Bensimon, Jean-Paul Vernant, Michelle Rosenzwajg, Dan A. Landau, Françoise Norol, David Klatzmann, Nathalie Dhedin, Helene Trebeden-Negre, José L. Cohen, and Madalina Uzunov
- Subjects
Adult ,Male ,CD4+CD25+ regulatory T cells ,Adolescent ,Regulatory T cell ,medicine.medical_treatment ,Graft vs Host Disease ,Bone Marrow Cells ,Cell Count ,Hematopoietic stem cell transplantation ,chemical and pharmacologic phenomena ,Disease ,T-Lymphocytes, Regulatory ,Clinical study ,Young Adult ,medicine ,Humans ,Young adult ,Bone Marrow Transplantation ,Retrospective Studies ,Bone marrow graft ,Transplantation ,business.industry ,Incidence ,Siblings ,Graft Survival ,hemic and immune systems ,Hematology ,Middle Aged ,Histocompatibility ,surgical procedures, operative ,medicine.anatomical_structure ,Acute Disease ,CD4 Antigens ,Immunology ,Female ,Bone marrow ,business ,Human - Abstract
The subpopulation of regulatory T cells (Treg) was shown to play a key role in alloreactive responses. In allogeneic hematopoietic stem cell transplantation, several groups tested whether Treg content in transplants correlates with graft-versus-host disease (GVHD) with controversial results. In a retrospective study of 49 consecutive HLA-matched sibling transplantations, we studied the relationship between Treg content in bone marrow transplants and acute GVHD (aGVHD) occurrence. We observed a large variability in Treg in bone marrow grafts. However, contrary to previous observations in peripheral blood stem cells transplantation, we report that the Treg content of allogeneic bone marrow transplantation did not predict the occurrence of aGVHD.
- Published
- 2011
49. Fully functional NK cells after unrelated cord blood transplantation
- Author
-
Vivien Béziat, Dominique Bories, Z. Marjanovic, Patrice Debré, Jean-Pierre Marie, Helene Trebeden-Negre, Baptiste Hervier, A. Boudifa, Françoise Norol, Bernard Rio, Madalina Uzunov, J P Vernant, Simona Lapusan, Vincent Vieillard, Nathalie Dhedin, and Stéphanie Nguyen
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Graft vs Leukemia Effect ,Biology ,Umbilical cord ,Immunophenotyping ,Natural killer cell ,Blood cell ,Young Adult ,Internal medicine ,medicine ,Humans ,Cytotoxicity ,Hematology ,Umbilical Cord Blood Transplantation ,Histocompatibility Testing ,Middle Aged ,Phenotype ,Tissue Donors ,Hematopoiesis ,Killer Cells, Natural ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Hematologic Neoplasms ,Immunology ,Female ,Cord Blood Stem Cell Transplantation ,Stem cell - Abstract
Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.
- Published
- 2009
50. Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia
- Author
-
N Jacque, J P Vernant, Veronique Leblond, Madalina Uzunov, Nathalie Dhedin, Stéphanie Nguyen, Dominique Bories, J-L Golmard, and Alice Garnier
- Subjects
Adult ,Male ,Myeloid ,Adolescent ,Real-Time Polymerase Chain Reaction ,Recurrence ,medicine ,Humans ,Indel ,Aged ,Retrospective Studies ,Transplantation ,Acute leukemia ,Transplantation Chimera ,business.industry ,food and beverages ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Allografts ,Peripheral blood ,Leukemia ,Leukemia, Myeloid, Acute ,Real-time polymerase chain reaction ,medicine.anatomical_structure ,Graft-versus-host disease ,Immunology ,Female ,business ,Stem Cell Transplantation - Abstract
Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; P0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.
- Published
- 2014
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.