34 results on '"Cornelissen, Jan J."'
Search Results
2. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT
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Stephane Vigouroux, Frédéric Baron, Didier Blaise, Christoph Schmid, Rainer Schwerdtfeger, Arnon Nagler, Noel Milpied, Michael Hallek, Fabio Ciceri, Sebastian Giebel, Emmanuelle Polge, Renate Arnold, Mohamad Mohty, Myriam Labopin, Bipin N. Savani, Boris V. Afanasyev, Dietger Niederwieser, Arnold Ganser, Norbert Claude Gorin, Jan J. Cornelissen, Jordi Esteve, Universitat de Barcelona, Hematology, Savani, Bipin N, Labopin, Myriam, Blaise, Didier, Niederwieser, Dietger, Ciceri, Fabio, Ganser, Arnold, Arnold, Renate, Afanasyev, Bori, Vigouroux, Stephane, Milpied, Noel, Hallek, Michael, Cornelissen, Jan J., Schwerdtfeger, Rainer, Polge, Emmanuelle, Baron, Frédéric, Esteve, Jordi, Gorin, Norbert C., Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon
- Subjects
Male ,Registrie ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Stem cells ,Gastroenterology ,Antineoplastic Agent ,0302 clinical medicine ,Recurrence ,Retrospective Studie ,Cumulative incidence ,Registries ,Transplantation, Homologou ,Bone Marrow Transplantation ,Acute leukemia ,Leukemia ,Hazard ratio ,Remission Induction ,Leucèmia ,Articles ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Treatment Outcome ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Female ,Survival Analysi ,Cèl·lules mare ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Prognosi ,Antineoplastic Agents ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Bone marrow ,Survival analysis ,Retrospective Studies ,Aged ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Survival Analysis ,Surgery ,Regimen ,Medul·la òssia ,business ,030215 immunology - Abstract
Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil >= 0.5x10(9) /L at day 60) was lower in bone marrow recipients: 88% versus 95% (P
3. Incidence and outcome of central nervous system relapse after hematopoietic stem cell transplantation in patients suffering from acute myeloid leukemia and acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Blum S, Chalandon Y, Labopin M, Finke J, Gedde-Dahl T, Othman TB, Cornelissen JJ, Jindra P, Labussière-Wallet H, Collin M, Lenhoff S, Kobbe G, Gutiérrez NC, Nagler A, and Mohty M
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- Humans, Incidence, Male, Adult, Female, Middle Aged, Adolescent, Europe epidemiology, Recurrence, Young Adult, Treatment Outcome, Aged, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Central Nervous System Neoplasms therapy
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- 2024
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4. High-risk additional cytogenetic aberrations in a Dutch chronic phase chronic myeloid leukemia patient population.
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Kockerols CCB, Geelen IGP, Levin MD, Janssen JJWM, Berna Beveloo H, Dinmohamed AG, Hoogendoorn M, Cornelissen JJ, and Westerweel PE
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- Humans, Cytogenetic Analysis, Chromosome Aberrations, Leukemia, Myeloid, Chronic-Phase drug therapy, Leukemia, Myeloid, Chronic-Phase genetics
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- 2023
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5. Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling.
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Lawless S, Iacobelli S, Knelange NS, Chevallier P, Blaise D, Milpied N, Foà R, Cornelissen JJ, Lioure B, Benjamin R, Poiré X, Minnema MC, Collin M, Lenhoff S, Snowden JA, Santarone S, Wilson KMO, Trigo F, Dreger P, Böhmer LH, Putter H, Garderet L, Kröger N, Yaukoub-Agha I, Schönland S, and Morris C
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- Humans, Retrospective Studies, Transplantation, Homologous, Disease-Free Survival, Transplantation, Autologous, Recurrence, Leukemia, Plasma Cell diagnosis, Leukemia, Plasma Cell therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.
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- 2023
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6. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation.
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Ruggeri A, De Wreede LC, Müller CR, Crivello P, Bonneville EF, Petersdorf EW, Socié G, Dubois V, Niittyvuopio R, Peräsaari J, Yakoub-Agha I, Cornelissen JJ, Wieten L, Gedde-Dahl T, Forcade E, Crawley CR, Marsh SGE, Gandemer V, Tholouli E, Bulabois CE, Huynh A, Choi G, Deconinck E, Itäla-Remes M, Lenhoff S, Bengtsson M, Johansson JE, Van Gorkom G, Hoogenboom JD, Vago L, Rocha V, Bonini C, Chabannon C, and Fleischhauer K
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- Humans, HLA-DP beta-Chains genetics, Histocompatibility Testing, Unrelated Donors, Alleles, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease etiology
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- 2023
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7. Treatment patterns and clinical outcomes of asciminib in a real-world multiresistant chronic myeloid leukemia patient population.
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Kockerols CCB, Janssen JJWM, Blijlevens NMA, Klein SK, Van Hussen-Daenen LGM, Van Gorkom GGY, Smit WM, Van Balen P, Biemond BJ, Cruijsen MJ, Corsten MF, Te Boekhorst PAW, Koene HR, Van Sluis GL, Cornelissen JJ, and Westerweel PE
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- Humans, Pyrazoles therapeutic use, Niacinamide therapeutic use, Protein Kinase Inhibitors therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid drug therapy
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- 2023
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8. The use of hydroxyurea pretreatment in chronic myeloid leukemia in the current tyrosine kinase inhibitor era.
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Kockerols CCB, Geelen I, Levin MD, Janssen JJWM, Dinmohamed AG, Hoogendoorn M, Cornelissen JJ, and Westerweel PE
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- Humans, Hydroxyurea therapeutic use, Protein Kinase Inhibitors therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid
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- 2022
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9. CD4+ T-cell alloreactivity after haploidentical hematopoietic stem cell transplantation.
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Kalin B, Metafuni E, Ter Borg M, Wijers R, Braakman E, Lamers CHJ, Bacigalupo A, and Cornelissen JJ
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- CD4-Positive T-Lymphocytes, Humans, Transplantation Conditioning, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation
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- 2021
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10. Allogeneic stem cell transplantation in second complete remission for core binding factor acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Halaburda K, Labopin M, Mailhol A, Socié G, Craddock C, Aljurf M, Beelen D, Cornelissen JJ, Bourhis JH, Labussière-Wallet H, Blaise D, Gedde-Dahl T, Gilleece M, Yakoub-Agha I, Mufti G, Esteve J, Mohty M, and Nagler A
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- Bone Marrow, Core Binding Factors genetics, Humans, Remission Induction, Retrospective Studies, Transplantation Conditioning, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
Core binding factor acute myeloid leukemia (AML) comprises two subtypes with distinct cytogenetic abnormalities of either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22). Since long-term response to chemotherapy in these leukemias is relatively good, allogeneic hematopoietic stem cell transplantation is considered in patients who relapse and achieve second complete remission. To evaluate the outcomes of allogeneic transplantation in this indication, we studied 631 patients reported to the European Society for Blood and Marrow Transplantation Registry between the years 2000 and 2014. Leukemia-free survival probabilities at two and five years were 59.1% and 54.1%, while overall survival probabilities were 65% and 58.2%, respectively. The incidence of relapse and risk of non-relapse mortality at the same time points were 19.8% and 22.5% for relapse and 20.9% and 23.3% for non-relapse mortality, respectively. The most important adverse factors influencing leukemia-free and overall survival were: leukemia with t(8;21), presence of three or more additional chromosomal abnormalities, and Karnofsky performance score <80. Relapse risk was increased in t(8;21) leukemia and associated with additional cytogenetic abnormalities as well as reduced intensity conditioning. Measurable residual disease in molecular evaluation before transplantation was associated with increased risk of relapse and inferior leukemia-free survival., (Copyright© 2020 Ferrata Storti Foundation.)
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- 2020
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11. Sorafenib improves survival of FLT3 -mutated acute myeloid leukemia in relapse after allogeneic stem cell transplantation: a report of the EBMT Acute Leukemia Working Party.
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Bazarbachi A, Labopin M, Battipaglia G, Djabali A, Passweg J, Socié G, Forcade E, Blaise D, Chevallier P, Orvain C, Cornelissen JJ, Arcese W, Chantepie S, Hashaishi K, El Cheikh J, Medinger M, Esteve J, Nagler A, and Mohty M
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- Adult, Aged, Antineoplastic Agents administration & dosage, Female, Gene Duplication, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Neoplasm Recurrence, Local, Registries, Remission Induction, Retrospective Studies, Salvage Therapy, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Mutation, Sorafenib administration & dosage, fms-Like Tyrosine Kinase 3 genetics
- Published
- 2019
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12. Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis.
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Robin M, Chevret S, Koster L, Wolschke C, Yakoub-Agha I, Bourhis JH, Chevallier P, Cornelissen JJ, Reményi P, Maertens J, Poiré X, Craddock C, Socié G, Itälä-Remes M, Schouten HC, Marchand T, Passweg J, Blaise D, Damaj G, Ozkurt ZN, Zuckerman T, Cluzeau T, Labussière-Wallet H, Cammenga J, McLornan D, Chalandon Y, and Kröger N
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- Aged, Antilymphocyte Serum pharmacology, Female, Graft vs Host Disease diagnosis, Humans, Immunosuppressive Agents pharmacology, Lymphocyte Depletion, Male, Middle Aged, Prognosis, Transplantation Conditioning, Transplantation, Haploidentical, Treatment Outcome, Antilymphocyte Serum therapeutic use, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Immunosuppressive Agents therapeutic use, Primary Myelofibrosis complications, Primary Myelofibrosis therapy, Siblings
- Abstract
The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft- versus -host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n=287). The cumulative incidences of grade II-IV acute graft- versus -host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft- versus -host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft- versus -host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P =0.010) while it did not decrease the risk of chronic graft- versus -host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P -values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft- versus -host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft- versus -host disease without increasing the risk of relapse., (Copyright© 2019 Ferrata Storti Foundation.)
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- 2019
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13. Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation.
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Gagelmann N, Eikema DJ, Stelljes M, Beelen D, de Wreede L, Mufti G, Knelange NS, Niederwieser D, Friis LS, Ehninger G, Nagler A, Yakoub-Agha I, Meijer E, Ljungman P, Maertens J, Kanz L, Lopez-Corral L, Brecht A, Craddock C, Finke J, Cornelissen JJ, Bernasconi P, Chevallier P, Sierra J, Robin M, and Kröger N
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- Adolescent, Adult, Aged, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy, Prognosis, Risk Factors, Survival Rate, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation mortality, Models, Statistical, Myelodysplastic Syndromes mortality, Nomograms, Risk Assessment standards
- Abstract
The aim of this study was to develop and validate a clinical and transplant-specific prognostic score using data from a large cohort of patients with myelodysplastic syndromes reported to the European Society for Blood and Marrow Transplantation registry. A Cox model was fitted to detect clinical and transplant-related variables prognostic of outcome. Then, cross-validation was performed to evaluate the validity and consistency of the model. Seven independent risk factors for survival were identified: age ≥50 years, matched unrelated donor, Karnofsky Performance Status <90%, very poor cytogenetics or monosomal karyotype, positive cytomegalovirus status of the recipient, blood blasts >1%, and platelet count ≤50 × 10
9 /L prior to transplantation. Incorporating these factors into a four-level risk score yielded hazard ratios for death, with low-risk (score of 0-1) as reference, of 2.02 (95% CI: 1.41-2.90) for the intermediate-risk group (score of 2-3), 3.49 (95% CI: 2.45-4.97) for the high-risk group (score of 4-5), and 5.90 (95% CI: 4.01-8.67) for the very high-risk group (score of >5). The score was predictive of survival, relapse-free survival, relapse, and non-relapse mortality ( P <0.001, respectively). Cross-validation yielded significant and reproducible improvement in prognostic ability with C-statistics being 0.609 (95% CI: 0.588-0.629) versus 0.555 for the Gruppo Italiano Trapianto di Midollo Osseo registry and 0.579 for the Center for Blood and Marrow Transplant Research registry. Prediction was even further augmented after applying a nomogram using age and platelets as continuous variables showing C-statistics of 0.628 (95% CI: 0.616-0.637). In conclusion, compared to existing prognostic systems, this proposed transplant-specific risk score offers improved performance with respect to post-transplant risk stratification in myelodysplastic syndromes., (Copyright© 2019 Ferrata Storti Foundation.)- Published
- 2019
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14. Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia.
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Polak R, Bierings MB, van der Leije CS, Sanders MA, Roovers O, Marchante JRM, Boer JM, Cornelissen JJ, Pieters R, den Boer ML, and Buitenhuis M
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- Autophagic Cell Death genetics, Child, Child, Preschool, Class III Phosphatidylinositol 3-Kinases genetics, Class III Phosphatidylinositol 3-Kinases metabolism, Core Binding Factor Alpha 2 Subunit genetics, Female, Humans, Male, Oncogene Proteins, Fusion genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Asparaginase pharmacology, Autophagic Cell Death drug effects, Core Binding Factor Alpha 2 Subunit metabolism, Drug Delivery Systems, Oncogene Proteins, Fusion metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Translocation t(12;21), resulting in the ETV6-RUNX1 (or TEL-AML1) fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia and is considered a first hit in leukemogenesis. A targeted therapy approach is not available for children with this subtype of leukemia. To identify the molecular mechanisms underlying ETV6-RUNX1-driven leukemia, we performed gene expression profiling of healthy hematopoietic progenitors in which we ectopically expressed ETV6-RUNX1. We reveal an ETV6-RUNX1-driven transcriptional network that induces proliferation, survival and cellular homeostasis. In addition, Vps34, an important regulator of autophagy, was found to be induced by ETV6-RUNX1 and up-regulated in ETV6-RUNX1-positive leukemic patient cells. We show that induction of Vps34 was transcriptionally regulated by ETV6-RUNX1 and correlated with high levels of autophagy. Knockdown of Vps34 in ETV6-RUNX1-positive cell lines severely reduced proliferation and survival. Inhibition of autophagy by hydroxychloroquine, a well-tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1-positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1-positive leukemia samples to L asparaginase. These findings reveal a causal relationship between ETV6-RUNX1 and autophagy, and provide pre-clinical evidence for the efficacy of autophagy inhibitors in ETV6-RUNX1-driven leukemia., (Copyright© 2019 Ferrata Storti Foundation.)
- Published
- 2019
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15. Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation.
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Schmid C, de Wreede LC, van Biezen A, Finke J, Ehninger G, Ganser A, Volin L, Niederwieser D, Beelen D, Alessandrino P, Kanz L, Schleuning M, Passweg J, Veelken H, Maertens J, Cornelissen JJ, Blaise D, Gramatzki M, Milpied N, Yakoub-Agha I, Mufti G, Rovira M, Arnold R, de Witte T, Robin M, and Kröger N
- Subjects
- Adolescent, Adult, Aged, Allografts, Europe, Female, Humans, Lymphocyte Transfusion, Male, Middle Aged, Myelodysplastic Syndromes therapy, Recurrence, Registries, Reoperation, Retrospective Studies, Risk Factors, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute etiology, Myelodysplastic Syndromes pathology
- Abstract
No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.7 months (95% confidence interval: 4.1-5.3) and the 2-year survival rate was 17.7% (95% confidence interval: 14.8-21.2%). Shorter remission after transplantation ( P <0.001), advanced disease ( P =0.001), older age ( P =0.007), unrelated donor ( P =0.008) and acute graft- versus -host disease before relapse ( P <0.001) adversely influenced survival. At 6 months from relapse, patients had received no cellular treatment, (i.e. palliative chemotherapy or best supportive care, n=375), donor lymphocyte infusion (n=213), or a second transplant (n=110). Treatment groups were analyzed separately because of imbalanced characteristics and difficulties in retrospectively evaluating the reason for individual treatments. Of the patients who did not receive any cellular therapy, 109 were alive at 6 months after relapse, achieving a median overall survival from this landmark of 8.9 months (95% confidence interval: 5.1-12.6). Their 2-year survival rate was 29.7%. Recipients of donor lymphocytes achieved a median survival from first infusion of 6.0 months (95% confidence interval: 3.7-8.3) with a 2-year survival rate of 27.6%. Longer remission after first transplantation ( P <0.001) and younger age ( P =0.009) predicted better outcome. Among recipients of a second transplant, the median survival from second transplantation was 4.2 months (95% confidence interval: 2.5-5.9), and their 2-year survival rate was 17.0%. Longer remission after first transplantation ( P <0.001), complete remission at second transplant ( P =0.008), no prior chronic graft- versus -host disease ( P <0.001) and change to a new donor ( P =0.04) predicted better outcome. The data enabled identification of patients benefiting from donor lymphocyte infusion and second transplantation, and may serve as a baseline for prospective trials., (Copyright© 2018 Ferrata Storti Foundation.)
- Published
- 2018
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16. Allogeneic stem cell transplantation benefits for patients ≥ 60 years with acute myeloid leukemia and FLT3 internal tandem duplication: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Poiré X, Labopin M, Polge E, Passweg J, Craddock C, Blaise D, Cornelissen JJ, Volin L, Russell NH, Socié G, Michallet M, Fegueux N, Chevallier P, Brecht A, Hunault-Berger M, Mohty M, Esteve J, and Nagler A
- Subjects
- Aged, Allografts, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Middle Aged, Prognosis, Risk Assessment, Survival Analysis, Gene Duplication, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, fms-Like Tyrosine Kinase 3 genetics
- Abstract
Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 ( FLT3 -ITD) is associated with a high risk of relapse, and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in the elderly, we made a selection from the European Society for Blood and Marrow Transplantation registry of de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3 -ITD in patients aged 60 or over and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%), while donors consisted of an unrelated donor in 161 (55%) patients. Two hundred and twelve patients received their transplantation in first remission, 37 in second remission and 42 in a more advanced stage of the disease. The 2-year leukemia-free survival rate was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively ( P <0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft- versus -host disease and relapse-free survival, and overall survival. In this elderly population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients ≥ 60 with FLT3 -ITD acute myeloid leukemia in first remission, similarly to current treatment recommendations for younger patients., (Copyright© 2018 Ferrata Storti Foundation.)
- Published
- 2018
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17. Impact of hospital experience on the quality of tyrosine kinase inhibitor response monitoring and consequence for chronic myeloid leukemia patient survival.
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Geelen IGP, Thielen N, Janssen JJWM, Hoogendoorn M, Roosma TJA, Willemsen SP, Valk PJM, Visser O, Cornelissen JJ, and Westerweel PE
- Subjects
- Adult, Aged, Aged, 80 and over, Drug Monitoring, Hospitals, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Middle Aged, Netherlands, Protein-Tyrosine Kinases antagonists & inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use
- Published
- 2017
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18. Treatment outcome in a population-based, 'real-world' cohort of patients with chronic myeloid leukemia.
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Geelen IGP, Thielen N, Janssen JJWM, Hoogendoorn M, Roosma TJA, Willemsen SP, Visser O, Cornelissen JJ, and Westerweel PE
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cohort Studies, Comorbidity, Disease Progression, Drug Substitution, Female, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Male, Middle Aged, Molecular Targeted Therapy, Mortality, Netherlands epidemiology, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors therapeutic use, Public Health Surveillance, Registries, Treatment Outcome, Leukemia, Myelogenous, Chronic, BCR-ABL Positive epidemiology
- Abstract
Evaluations of the 'real-world' efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide, population-based, chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagnosed between January 2008 and April 2013 in the Netherlands. The registry covered 457 patients; 434 in chronic phase (95%) and 15 (3%) in advanced disease phase. Seventy-five percent of the patients in chronic phase were treated with imatinib and 25% with a second-generation tyrosine kinase inhibitor. At 3 years 44% of patients had discontinued their first-line treatment, mainly due to intolerance (21%) or treatment failure (19%). At 18 months 73% of patients had achieved a complete cytogenetic response and 63% a major molecular response. Deep molecular responses (MR
4.0 and MR4.5 ) were achieved in 69% and 56% of patients, respectively, at 48 months. All response milestones were achieved faster in patients treated upfront with a second-generation tyrosine kinase inhibitor, but ultimately patients initially treated with imatinib also reached similar levels of responses. The 6-year cumulative incidence of eligibility for a tyrosine kinase cessation attempt, according to EURO-SKI criteria, was 31%. Our findings show that in a 'real-world' setting the long-term outcome of patients treated with tyrosine kinase inhibitors is excellent and the conditions for an attempt to stop tyrosine kinase inhibitor therapy are met by a third of the patients., (Copyright© Ferrata Storti Foundation.)- Published
- 2017
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19. The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent.
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van Walraven SM, Brand A, Bakker JN, Heemskerk MB, Nillesen S, Bierings MB, Bungener LB, Hepkema BG, Lankester A, van der Meer A, Sintnicolaas K, Somers JA, Spierings E, Tilanus MG, Voorter CE, Cornelissen JJ, and Oudshoorn M
- Subjects
- Adolescent, Adult, Child, Female, Histocompatibility Testing, Humans, Male, Neoplasms diagnosis, Neoplasms epidemiology, Neoplasms therapy, Netherlands, Population Groups, Young Adult, Hematopoietic Stem Cell Transplantation statistics & numerical data, Registries, Tissue Donors
- Abstract
Between 2001 and 2012, the number of unrelated donors registered worldwide increased from 7 to 21 million, and the number of public cord blood units increased to over 500,000. We addressed the question of whether this expansion resulted in higher percentages of patients reaching transplantation. Unrelated donor searches were evaluated for 3,124 eligible patients in the Netherlands in two cohorts (2001-2006, n=995; 2007-2012, n=2129), comparing results for patients of Northwestern European and non-Northwestern European origin. Endpoints were 'donor found' and 'transplantation reached'. The substantial growth of the donor inventory over the period studied did not increase the median number of potential unrelated donors (n=7) for non-Northwestern European patients, but almost doubled the number for Northwestern European patients from 42 to 71. Before and after 2007, an unrelated donor or cord blood was identified for 91% and 95%, respectively, of Northwestern European patients and for 65% and 82% of non-Northwestern European patients (P<0.0001). Non-Northwestern European patients more often needed a cord blood transplant. The degree of HLA matching was significantly lower for non-Northwestern European patients (P<0.0006). The time needed to identify a donor decreased for both populations. The percentage of Northwestern European patients reaching transplantation increased from 77% to 83% and for non-Northwestern European patients from 57% to 72% (P=0.0003). The increase of the global inventory resulted in more transplants for patients lacking a family donor, although the quality and quantity of (potential) haematopoietic cell grafts for patients of a non-Northwestern European descent remained inferior, indicating the need for adaptation of recruitment., (Copyright© Ferrata Storti Foundation.)
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- 2017
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20. Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT.
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Paviglianiti A, Xavier E, Ruggeri A, Ceballos P, Deconinck E, Cornelissen JJ, Nguyen-Quoc S, Maillard N, Sanz G, Rohrlich PS, Garderet L, Volt F, Rocha V, Kroeger N, Gluckman E, Fegueux N, and Mohty M
- Subjects
- Adult, Aged, Combined Modality Therapy, Female, Follow-Up Studies, Graft Survival, Graft vs Host Disease etiology, Humans, Male, Middle Aged, Mortality, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma mortality, Recurrence, Registries, Retrospective Studies, Treatment Outcome, Young Adult, Cord Blood Stem Cell Transplantation adverse effects, Cord Blood Stem Cell Transplantation methods, Multiple Myeloma therapy, Unrelated Donors
- Abstract
Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients., (Copyright© Ferrata Storti Foundation.)
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- 2016
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21. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT.
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Savani BN, Labopin M, Blaise D, Niederwieser D, Ciceri F, Ganser A, Arnold R, Afanasyev B, Vigouroux S, Milpied N, Hallek M, Cornelissen JJ, Schwerdtfeger R, Polge E, Baron F, Esteve J, Gorin NC, Schmid C, Giebel S, Mohty M, and Nagler A
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Agents therapeutic use, Female, Graft vs Host Disease genetics, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prognosis, Recurrence, Remission Induction, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Bone Marrow Transplantation, Graft vs Host Disease diagnosis, Leukemia, Myeloid, Acute diagnosis, Peripheral Blood Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Registries, Transplantation Conditioning methods
- Abstract
Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil ≥0.5×10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts. However, there is an increase in chronic graft-versus-host disease after peripheral blood grafts. Long-term follow up is needed to clarify whether chronic graft-versus-host disease might increase the risk of late morbidity and mortality., (Copyright© Ferrata Storti Foundation.)
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- 2016
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22. Monosomal karyotype as an adverse prognostic factor in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem-cell transplantation in first complete remission: a retrospective survey on behalf of the ALWP of the EBMT.
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Brands-Nijenhuis AV, Labopin M, Schouten HC, Volin L, Socié G, Cornelissen JJ, Huynh A, Ljungman P, Malard F, Esteve J, Nagler A, and Mohty M
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Agents therapeutic use, Female, Humans, Karyotyping, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Multivariate Analysis, Prognosis, Recurrence, Remission Induction, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Monosomy pathology, Registries, Transplantation Conditioning methods
- Abstract
Despite the overall benefit from allogeneic hematopoietic stem cell transplantation observed in patients with poor cytogenetic risk acute myeloid leukemia in first complete remission, the precise effect of this procedure for different poor-risk subtypes has not been fully analyzed. This retrospective analysis was performed to investigate whether allogeneic hematopoietic stem cell transplantation performed in first complete remission in patients with monosomal karyotype can overcome the adverse prognosis associated with these patients. Of the 4635 patients included in the study, 189 (4%) harbored a monosomal karyotype. The presence of a monosomal karyotype was associated with a worse outcome, with an inferior leukemia-free survival and overall survival (5-year leukemia-free survival and overall survival: 24 ± 3% and 26 ± 3% vs. 53 ± 1% and 57 ± 1% in monosomal-karyotype and non-monosomal-karyotype, respectively; P<0.0001) and higher relapse risk after transplantation (cumulative incidence of relapse at 5 years: 56 ± 4% in monosomal-karyotype vs. 28 ± 1% in non-monosomal-karyotype; P<0.0001). The adverse negative impact of monosomal karyotype cytogenetics was confirmed in the entire cohort in a multivariate analysis [Hazard Ratio (HR): 1.88, 95% Confidence Interval (CI):1.29-2.73, P=0.001 for relapse incidence; HR:1.71, 95%CI:1.27-2.32, P<0.0001 for leukemia-free survival; HR:1.81, 95%CI:1.32-2.48, P=0.0002 for overall survival], and was independent of the presence of other poor-risk cytogenetic subtypes. In summary, monosomal karyotype arises as a strong negative prognostic feature in acute myeloid leukemia also in patients who undergo allogeneic hematopoietic stem cell transplantation in first complete remission, stressing the need to develop additional pre- and post-transplantation strategies aimed at improving overall results. Nonetheless, allogeneic hematopoietic stem cell transplantation in early phase is currently the best therapy for this very poor-risk acute myeloid leukemia subtype., (Copyright© Ferrata Storti Foundation.)
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- 2016
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23. Reduced relapse rate in upfront tandem autologous/reduced-intensity allogeneic transplantation in multiple myeloma only results in borderline non-significant prolongation of progression-free but not overall survival.
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Lokhorst HM, van der Holt B, Cornelissen JJ, Kersten MJ, van Oers M, Raymakers R, Minnema MC, Zweegman S, Bos G, Schaap N, Wittebol S, de Weerdt O, Ammerlaan R, and Sonneveld P
- Subjects
- Allografts, Autografts, Disease-Free Survival, Female, Humans, Male, Survival Rate, Multiple Myeloma mortality, Multiple Myeloma therapy, Stem Cell Transplantation
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- 2015
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24. Expression profiling of adult acute lymphoblastic leukemia identifies a BCR-ABL1-like subgroup characterized by high non-response and relapse rates.
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Boer JM, Koenders JE, van der Holt B, Exalto C, Sanders MA, Cornelissen JJ, Valk PJ, den Boer ML, and Rijneveld AW
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- Adolescent, Adult, Aged, Fusion Proteins, bcr-abl metabolism, Gene Expression, Gene Expression Profiling, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism, Humans, Ikaros Transcription Factor genetics, Ikaros Transcription Factor metabolism, Middle Aged, Mutation, Myeloid-Lymphoid Leukemia Protein genetics, Myeloid-Lymphoid Leukemia Protein metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Protein Kinase Inhibitors therapeutic use, Recurrence, Remission Induction, Survival Analysis, Transplantation, Homologous, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl genetics, Hematopoietic Stem Cell Transplantation, Imatinib Mesylate therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
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- 2015
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25. Circulating endothelial cell enumeration demonstrates prolonged endothelial damage in recipients of myeloablative allogeneic stem cell transplantation.
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Beije N, Versluis J, Kraan J, Gratama JW, Sleijfer S, and Cornelissen JJ
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- Adult, Aged, Female, Hematopoietic Stem Cell Transplantation trends, Humans, Male, Middle Aged, Retrospective Studies, Transplantation Conditioning trends, Transplantation, Homologous adverse effects, Transplantation, Homologous trends, Young Adult, Endothelial Cells metabolism, Endothelium, Vascular pathology, Hematopoietic Stem Cell Transplantation adverse effects, Myeloablative Agonists administration & dosage, Transplantation Conditioning adverse effects
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- 2015
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26. Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.
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Brissot E, Labopin M, Beckers MM, Socié G, Rambaldi A, Volin L, Finke J, Lenhoff S, Kröger N, Ossenkoppele GJ, Craddock CF, Yakoub-Agha I, Gürman G, Russell NH, Aljurf M, Potter MN, Nagler A, Ottmann O, Cornelissen JJ, Esteve J, and Mohty M
- Subjects
- Adolescent, Adult, Aged, Female, Histocompatibility Testing, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Prognosis, Remission Induction, Retrospective Studies, Siblings, Survival Analysis, Time Factors, Transplantation, Homologous, Treatment Outcome, Unrelated Donors, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting., (Copyright© Ferrata Storti Foundation.)
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- 2015
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27. Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study.
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Somers JA, Braakman E, van der Holt B, Petersen EJ, Marijt EW, Huisman C, Sintnicolaas K, Oudshoorn M, Groenendijk-Sijnke ME, Brand A, and Cornelissen JJ
- Subjects
- Adult, Aged, Female, Graft Survival, Graft vs Host Disease etiology, Hematologic Neoplasms diagnosis, Hematologic Neoplasms mortality, Humans, Male, Middle Aged, Prognosis, Risk Factors, Treatment Outcome, Whole-Body Irradiation, Young Adult, Cord Blood Stem Cell Transplantation adverse effects, Hematologic Neoplasms therapy, Transplantation Chimera, Transplantation Conditioning methods
- Abstract
Double umbilical cord blood transplantation is increasingly applied in the treatment of adult patients with high-risk hematological malignancies and has been associated with improved engraftment as compared to that provided by single unit cord blood transplantation. The mechanism of improved engraftment is, however, still incompletely understood as only one unit survives. In this multicenter phase II study we evaluated engraftment, early chimerism, recovery of different cell lineages and transplant outcome in 53 patients who underwent double cord blood transplantation preceded by a reduced intensity conditioning regimen. Primary graft failure occurred in one patient. Engraftment was observed in 92% of patients with a median time to neutrophil recovery of 36 days (range, 15-102). Ultimate single donor chimerism was established in 94% of patients. Unit predominance occurred by day 11 after transplantation and early CD4(+) T-cell chimerism predicted for unit survival. Total nucleated cell viability was also associated with unit survival. With a median follow up of 35 months (range, 10-51), the cumulative incidence of relapse and non-relapse mortality rate at 2 years were 39% and 19%, respectively. Progressionfree survival and overall survival rates at 2 years were 42% (95% confidence interval, 28-56) and 57% (95% confidence interval, 43-70), respectively. Double umbilical cord blood transplantation preceded by a reduced intensity conditioning regimen using cyclophosphamide/fludarabine/4 Gy total body irradiation results in a high engraftment rate with low non-relapse mortality. Moreover, prediction of unit survival by early CD4(+) lymphocyte chimerism might suggest a role for CD4(+) lymphocyte mediated unit-versus-unit alloreactivity. www.trialregister.nl NTR1573., (Copyright© Ferrata Storti Foundation.)
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- 2014
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28. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood.
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Rodrigues CA, Rocha V, Dreger P, Brunstein C, Sengeloev H, Finke J, Mohty M, Rio B, Petersen E, Guilhot F, Niederwieser D, Cornelissen JJ, Jindra P, Nagler A, Fegueux N, Schoemans H, Robinson S, Ruggeri A, Gluckman E, Canals C, and Sureda A
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Follow-Up Studies, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Cord Blood Stem Cell Transplantation, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Unrelated Donors
- Abstract
We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P<0.0001) and chronic graft-versus-host disease (26% vs. 52%; P=0.0005) were less frequent after unrelated cord blood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28%), and relapse or progression (28% vs. 35%) at 36 months. There were also no significant differences in 2-year progression-free survival (43% vs. 58%, respectively) and overall survival (36% vs. 51%) at 36 months. In a multivariate analysis, no differences were observed in the outcomes between the two stem cell sources except for a higher risk of neutrophil engraftment (hazard ratio=2.12; P<0.0001) and chronic graft-versus-host disease (hazard ratio 2.10; P=0.0002) after matched unrelated donor transplant. In conclusion, there was no difference in final outcomes after transplantation between umbilical cord blood and matched unrelated donor transplant. Umbilical cord blood is a valuable alternative for patients with lymphoid malignancies lacking an HLA-matched donor, being associated with lower risk of chronic graft-versus-host disease.
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- 2014
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29. Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients.
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Wils EJ, van der Holt B, Broers AE, Posthumus-van Sluijs SJ, Gratama JW, Braakman E, and Cornelissen JJ
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- Adolescent, Adult, Disease-Free Survival, Female, Follow-Up Studies, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Incidence, Male, Middle Aged, Opportunistic Infections etiology, Risk Factors, Survival Rate, Time Factors, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Opportunistic Infections immunology, Opportunistic Infections mortality, Recovery of Function immunology, Thymus Gland immunology
- Abstract
Background: Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality., Design and Methods: A detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning. Recovery of thymopoiesis was assessed using analysis of signal joint T-cell receptor rearrangement excision circles. The impact of recovery of thymopoiesis at 2, 6, 9 and 12 months post-transplantation on clinical outcome beyond those time points was evaluated by univariate and multivariate Cox regression analyses., Results: The cumulative incidence of severe infections at 12 months after transplantation was 66% with a median number of 1.64 severe infectious episodes per patient. Patients in whom thymopoiesis did not recover were at significantly higher risk of severe infections according to multivariable analysis. Hazard ratios indicated 3- and 9-fold increases in severe infections at 6 and 12 months, respectively. Impaired recovery of thymopoiesis also translated into a higher risk of non-relapse mortality and outweighed pre-transplant risk factors including age, donor type, and disease risk-status., Conclusions: These results indicate that patients who fail to recover thymopoiesis after allogeneic hematopoietic stem cell transplantation are at very high risk of severe infections and adverse clinical outcome.
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- 2011
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30. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia.
- Author
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Deenik W, Janssen JJ, van der Holt B, Verhoef GE, Smit WM, Kersten MJ, Daenen SM, Verdonck LF, Ferrant A, Schattenberg AV, Sonneveld P, van Marwijk Kooy M, Wittebol S, Willemze R, Wijermans PW, Beverloo HB, Löwenberg B, Valk PJ, Ossenkoppele GJ, and Cornelissen JJ
- Subjects
- Adult, Aged, Benzamides, Cytogenetic Analysis, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Middle Aged, Treatment Outcome, Young Adult, Cytarabine administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines administration & dosage, Pyrimidines administration & dosage
- Abstract
Background: In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study., Design and Methods: Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1 to 7) in 162 patients with chronic myeloid leukemia., Results: With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50-0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96-2.68, P=0.07) and 1.66 (95% confidence interval, 1.02-2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%., Conclusions: The addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: NCT00028847).
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- 2010
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31. Methylation patterns in CD34 positive chronic myeloid leukemia blast crisis cells.
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Janssen JJ, Denkers F, Valk P, Cornelissen JJ, Schuurhuis GJ, and Ossenkoppele GJ
- Subjects
- Adolescent, Adult, Aged, Antigens, CD34 genetics, Blast Crisis genetics, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Middle Aged, Antigens, CD34 metabolism, Blast Crisis metabolism, Blast Crisis pathology, DNA Methylation physiology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
- Published
- 2010
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32. IL-7-mediated protection against minor-antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells.
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Broers AE, Bruinsma M, Posthumus-van Sluijs SJ, Wils EJ, Spits H, Löwenberg B, Braakman E, and Cornelissen JJ
- Subjects
- Animals, Animals, Congenic, CD4 Antigens analysis, Drug Evaluation, Preclinical, Forkhead Transcription Factors biosynthesis, Forkhead Transcription Factors genetics, Graft Rejection immunology, Interleukin-2 Receptor alpha Subunit analysis, Interleukin-7 pharmacology, Interleukin-7 Receptor alpha Subunit biosynthesis, Interleukin-7 Receptor alpha Subunit genetics, Lymphocyte Count, Lymphocyte Depletion, Mice, Mice, Inbred Strains, Mice, Knockout, Recombinant Proteins therapeutic use, Specific Pathogen-Free Organisms, T-Lymphocytes, Regulatory drug effects, Transplantation, Homologous, Bone Marrow Transplantation immunology, Graft Rejection prevention & control, Host vs Graft Reaction drug effects, Interleukin-7 therapeutic use, Minor Histocompatibility Antigens immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Background and Objectives: Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity., Design and Methods: To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts., Results: Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration., Interpretation and Conclusions: Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recovery.
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- 2007
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33. Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial.
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Sonneveld P, van der Holt B, Segeren CM, Vellenga E, Croockewit AJ, Verhoe GE, Cornelissen JJ, Schaafsma MR, van Oers MH, Wijermans PW, Westveer PH, and Lokhorst HM
- Subjects
- Adolescent, Adult, Aged, Follow-Up Studies, Humans, Middle Aged, Multiple Myeloma mortality, Netherlands, Remission Induction, Survival Analysis, Melphalan administration & dosage, Multiple Myeloma drug therapy, Myeloablative Agonists administration & dosage
- Abstract
Background and Objectives: The Dutch-Belgian HOVON group performed a randomized phase 3 trial to compare single non-myeloablative intensive treatment with double, intensive treatment in previously untreated patients with multiple myeloma (MM)., Design and Methods: Three hundred and three patients with stage II/III MM were randomized after VAD induction chemotherapy to receive two cycles of non-myeloablative intermediate-dose melphalan (70 mg/m2) (single treatment) or the same regimen followed by cyclophosphamide 120 mg/kg iv plus total body irradiation (TBI) 9 Gy and autologous stem cell transplantation (double, intensive treatment). In both treatment arms interferon .IIa was given as maintenance until relapse/progression., Results: A significantly higher proportion of patients achieved a complete remission (CR) on protocol treatment with double, intensive therapy (32 % vs 13 %, p<0.001). Double treatment produced better outcome in terms of event-free survival (median 22 vs 21 months, 28% vs 14% at 4 years and 15% vs 7% at 6 years after randomization; logrank p=0.013; univariate HR 0.74, 95% CI, 0.58-0.94), progression-free survival (median 27 vs 24 months, 33% vs 16% at 4 years, and 17% vs 9% at 6 years after randomization; logrank p=0.006; HR=0.71, 95% CI 0.56-0.91), but not overall survival (median 50 vs 55 months, 52% vs 56% at 4 years and 39% vs 36% at 6 years after randomization; logrank p=0.51; HR=1.10, 95% CI 0.83-1.46). The achievement of a CR had a favorable prognostic impact on event-free survival (HR=0.60 , 95% CI=0.44 -0.82 , p=0.001) and progression-free survival (HR=0.62 , 95% CI=0.45 -0.84, p=0.002)., Interpretation and Conclusions: Double, intensive treatment resulted in a better CR rate, event-free survival and progression-free survival but not overall survival compared to single non-myeloablative treatment in previously untreated patients with multiple myeloma.
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- 2007
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34. Allogeneic stem cell transplantation for patients with acute myeloid leukemia or myelodysplastic syndrome who have chromosome 5 and/or 7 abnormalities.
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van der Straaten HM, van Biezen A, Brand R, Schattenberg AV, Egeler RM, Barge RM, Cornelissen JJ, Schouten HC, Ossenkoppele GJ, and Verdonck LF
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Disease-Free Survival, Female, Humans, Infant, Leukemia, Myeloid, Acute surgery, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes surgery, Retrospective Studies, Transplantation, Homologous, Chromosome Aberrations, Chromosomes, Human, Pair 5 genetics, Chromosomes, Human, Pair 7 genetics, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics, Stem Cell Transplantation
- Abstract
Background and Objectives: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on allogeneic SCT in this context are limited we did a retrospective study of allogeneic SCT in patients with AML or MDS who had chromosome 5 and/or 7 abnormalities., Design and Methods: This was a retrospective study of 65 patients (16 children, 49 adults) with AML (n=33) or MDS (n=32) who had chromosome 5 and/or 7 abnormalities and who underwent allogeneic SCT in six Dutch Centers between 1983 and 2001. Data on all these patients are recorded in the Netherlands Stem Cell Transplant Registry (Typhon)., Results: The 3-year overall survival rate among all patients was 25%. Patients below the age of 40 years had significantly fewer relapses (40%) and better survival (38%) than those above the age of 40 (86% and 8%, respectively). Relapses were less frequent in recipients of unrelated grafts than in those whose grafts were from HLA-identical siblings (30% versus 69%). The development of acute graft-versus-host disease (GVHD) grades II-IV was independently associated with significantly higher transplant-related mortality (TRM). Patients with either chromosome 5 or chromosome 7 abnormalities had a significantly better survival than patients with both chromosome 5 and 7 abnormalities. These patients with poor-risk chromosome 5 and/or 7 abnormalities were compared with a group of patients with a secondary AML/MDS and normal cytogenetics and were found to have significantly more relapses and significantly worse survival but a similar TRM., Interpretation and Conclusions: We conclude that patients with AML or MDS with chromosome 5 and/or 7 abnormalities do rather poorly after allogeneic SCT, mainly because of the very high relapse rate. Nevertheless, this is the only approach that can cure some of these patients.
- Published
- 2005
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