149 results on '"Leukemia relapse"'
Search Results
2. Decitabine Plus mBU/CY for High Risk Acute Leukemia With MRD Pre-HSCT
- Author
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Xiaojun Huang,MD, Director of the Hematology Department
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- 2020
3. Synapse topology and downmodulation events determine the functional outcome of anti-CD19 T cell-redirecting strategies
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Ángel Ramírez-Fernández, Óscar Aguilar-Sopeña, Laura Díez-Alonso, Alejandro Segura-Tudela, Carmen Domínguez-Alonso, Pedro Roda-Navarro, Luis Álvarez-Vallina, and Belén Blanco
- Subjects
CD19+ B cell malignancies ,T cell-redirecting strategies ,STAb ,BiTE ,CAR ,leukemia relapse ,Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer immunotherapy strategies based on the endogenous secretion of T cell-redirecting bispecific antibodies by engineered T lymphocytes (STAb-T) are emerging as alternative or complementary approaches to those based on chimeric antigen receptors (CAR-T). The antitumor efficacy of bispecific anti-CD19 × anti-CD3 (CD19×CD3) T cell engager (BiTE)-secreting STAb-T cells has been demonstrated in several mouse models of B-cell acute leukemia. Here, we have investigated the spatial topology and downstream signaling of the artificial immunological synapses (IS) that are formed by CAR-T or STAb-T cells. Upon interaction with CD19-positive target cells, STAb-T cells form IS with structure and signal transduction, which more closely resemble those of physiological cognate IS, compared to IS formed by CAR-T cells expressing a second-generation CAR bearing the same CD19-single-chain variable fragment. Importantly, while CD3 is maintained at detectable levels on the surface of STAb-T cells, indicating sustained activation mediated by the secreted BiTE, the anti-CD19 CAR was rapidly downmodulated, which correlated with a more transient downstream signaling. Furthermore, CAR-T cells, but not STAb-T cells, provoke an acute loss of CD19 in target cells. Such differences might represent advantages of the STAb-T strategy over the CAR-T approach and should be carefully considered in order to develop more effective and safer treatments for hematological malignancies.
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- 2022
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4. Synapse topology and downmodulation events determine the functional outcome of anti-CD19 T cell-redirecting strategies.
- Author
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Ramírez-Fernández, Ángel, Aguilar-Sopeña, Óscar, Díez-Alonso, Laura, Segura-Tudela, Alejandro, Domínguez-Alonso, Carmen, Roda-Navarro, Pedro, Álvarez-Vallina, Luis, and Blanco, Belén
- Subjects
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BISPECIFIC antibodies , *SYNAPSES , *CHIMERIC antigen receptors , *T cells , *HEMATOLOGIC malignancies - Abstract
Cancer immunotherapy strategies based on the endogenous secretion of T cell-redirecting bispecific antibodies by engineered T lymphocytes (STAb-T) are emerging as alternative or complementary approaches to those based on chimeric antigen receptors (CAR-T). The antitumor efficacy of bispecific anti-CD19 × anti-CD3 (CD19×CD3) T cell engager (BiTE)-secreting STAb-T cells has been demonstrated in several mouse models of B-cell acute leukemia. Here, we have investigated the spatial topology and downstream signaling of the artificial immunological synapses (IS) that are formed by CAR-T or STAb-T cells. Upon interaction with CD19-positive target cells, STAb-T cells form IS with structure and signal transduction, which more closely resemble those of physiological cognate IS, compared to IS formed by CAR-T cells expressing a second-generation CAR bearing the same CD19-single-chain variable fragment. Importantly, while CD3 is maintained at detectable levels on the surface of STAb-T cells, indicating sustained activation mediated by the secreted BiTE, the anti-CD19 CAR was rapidly downmodulated, which correlated with a more transient downstream signaling. Furthermore, CAR-T cells, but not STAb-T cells, provoke an acute loss of CD19 in target cells. Such differences might represent advantages of the STAb-T strategy over the CAR-T approach and should be carefully considered in order to develop more effective and safer treatments for hematological malignancies. [ABSTRACT FROM AUTHOR]
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- 2022
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5. The unnecessary use of short tandem repeat testing on bone marrow samples in patients after 1 year following allogeneic hematopoietic stem cell transplant.
- Author
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Morris AB, Sullivan HC, Wooten MS, Waller EK, and Jaye DL
- Abstract
Objectives: To determine whether the information provided by short tandem repeat (STR) testing and bone marrow (BM) biopsy specimens following hematopoietic stem cell transplant (HSCT) provides redundant information, leading to test overutilization, without additional clinical benefit., Methods: Cases with synchronous STR and flow cytometric immunophenotyping (FCI) testing, as part of the BM evaluation, were assessed for STR/FCI concordance., Results: Of 1199 cases (410 patients), we found the overall concordance between STR and FCI was 93%, with most cases (1063) classified as STR-/FCI-. Of all discordant cases, 75 (6%) were STR+/FCI-, with only 5 (6.7%) cases best explained as identification of disease relapse. Eight cases were STR-/FCI+, representing relapsed/residual disease. Analysis of cases 1 year or more from transplant (54% of all cases) indicated only 9 (1.5%) were STR+/FCI-, and none uniquely identified relapse., Conclusions: These data suggest that STR analysis performed 1 year or more post-HSCT does not identify unknown cases of relapse. Furthermore, while STR testing is critical for identifying graft failure/rejection within the first year posttransplant, FCI appears superior to STR at detecting late relapses with low-level disease. Therefore, STR testing from patients 1 year or more post-HSCT may be unnecessary, as BM biopsy evaluation is sufficient to identify disease relapse., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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6. A Optimal Anti-Thymoglobuline (ATG) Dose Decrease cGVHD But Not Increase Leukemia Relapse for Haplo-HSCT
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Nanfang Hospital, Southern Medical University, First Affiliated Hospital, Sun Yat-Sen University, and Second Affiliated Hospital, Sun Yat-Sen University
- Published
- 2017
7. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT
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Simona Piemontese, Ariane Boumendil, Myriam Labopin, Christoph Schmid, Fabio Ciceri, William Arcese, Yener Koc, Zafar Gulbas, Johanna Tischer, Benedetto Bruno, Depei Wu, Didier Blaise, Dietrich Beelen, Giuseppe Irrera, Annalisa Ruggeri, Mohamed Houhou, Mohamad Mohty, Arnon Nagler, and on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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Leukemia relapse ,Survival after relapse ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Methods Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. Results The cumulative incidence of relapse at 3 years was 44% (35–53%) for ALL and 32% (27–36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). Conclusions Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%).
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- 2019
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8. Comparison of post-remission strategies in acute myeloid leukemia: Autologous hematopoietic stem cell transplantation versus consolidation chemotherapy
- Author
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Zeynep Arzu Yegin, Asena Dikyar, Lale Aydın Kaynar, Ferda Can, Zübeyde Nur Özkurt, and Münci Yağcı
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Acute Myeloid Leukemia ,Autologous Hematopoietic Stem Cell Transplantation ,Consolidation Chemotherapy ,Leukemia Relapse ,Prognosis ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has become a therapeutic option for first-line consolidation in Acute Myeloid Leukemia (AML) patients with favorable and intermediate risk features. A total of 101 AML patients in first complete remission, who were not eligible for allogeneic HSCT, were randomized to receive intensive cytarabine-based chemotherapy or to undergo auto-HSCT. The probability of LFS was significantly better in auto-HSCT recipients compared to chemotherapy arm (43% vs 4.8%, p=0.008). At the end of 915 (30-4470) days of followup, the probability of overall survival was better in auto-HSCT group compared to chemotherapy, without statistical significance (79.2% vs 38.8%, p=0.054). Multivariate analysis revealed a significant predictive impact of cytogenetic risk status on OS (p=0.002, HR: 2.824, 95% CI: 1.445- 5.521). Auto-HSCT is considered as an effective consolidation approach in favorable and intermadiate risk AML patients.
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- 2020
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9. Comparison of post-remission strategies in acute myeloid leukemia: Autologous hematopoietic stem cell transplantation versus consolidation chemotherapy.
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Yegin, Zeynep Arzu, Dikyar, Asena, Kaynar, Lale Aydın, Can, Ferda, Özkurt, Zübeyde Nur, and Yağcı, Münci
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HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia , *CONSOLIDATION chemotherapy - Abstract
Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has become a therapeutic option for first-line consolidation in Acute Myeloid Leukemia (AML) patients with favorable and intermediate risk features. A total of 101 AML patients in first complete remission, who were not eligible for allogeneic HSCT, were randomized to receive intensive cytarabine-based chemotherapy or to undergo auto-HSCT. The probability of LFS was significantly better in auto-HSCT recipients compared to chemotherapy arm (43% vs 4.8%, p=0.008). At the end of 915 (30-4470) days of followup, the probability of overall survival was better in auto-HSCT group compared to chemotherapy, without statistical significance (79.2% vs 38.8%, p=0.054). Multivariate analysis revealed a significant predictive impact of cytogenetic risk status on OS (p=0.002, HR: 2.824, 95% CI: 1.445- 5.521). Auto-HSCT is considered as an effective consolidation approach in favorable and intermadiate risk AML patients. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Haploidentical Haematopoietic Stem Cell Transplantation: Role of NK Cells and Effect of Cytomegalovirus Infections
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Della Chiesa, Mariella, Moretta, Lorenzo, Muccio, Letizia, Bertaina, Alice, Moretta, Francesca, Locatelli, Franco, Moretta, Alessandro, Compans, Richard W, Series editor, Cooper, Max D., Series editor, Honjo, Tasuku, Series editor, Oldstone, Michael B. A., Series editor, Vogt, Peter K., Series editor, Malissen, Bernard, Series editor, Aktories, Klaus, Series editor, Kawaoka, Yoshihiro, Series editor, Rappuoli, Rino, Series editor, Galan, Jorge E., Series editor, Ahmed, Rafi, Series editor, Vivier, Eric, editor, Di Santo, James, editor, and Moretta, Alessandro, editor
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- 2016
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11. Post-Irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: A Retrospective Single-Centre Cohort Analysis
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Francesco Baldo, Roberto Simeone, Annalisa Marcuzzi, Antonio Giacomo Grasso, Rossella Vidimari, Francesca Ciriello, Davide Zanon, Alessandra Maestro, Egidio Barbi, and Natalia Maximova
- Subjects
total body irradiation ,total amylase ,proinflammatory cytokines ,hematopoietic stem cell transplantation ,overall survival ,leukemia relapse ,Medicine - Abstract
Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient’s age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773; 95% CI = 0.66–0.86; p < 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865; 95% CI = 0.77–0.93; p < 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-α, IL-6, and RANTES (p < 0.001). Conclusions: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.
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- 2021
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12. Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
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Chen-Hua Yan, Yu Wang, Jing-Zhi Wang, Yu-Hong Chen, Yao Chen, Feng-rong Wang, Yu-Qian Sun, Xiao-Dong Mo, Wei Han, Huan Chen, Xiao-hui Zhang, Lan-Ping Xu, Kai-Yan Liu, and Xiao-Jun Huang
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Allogeneic hematopoietic stem cell transplant ,Leukemia relapse ,Acute leukemia ,Donor lymphocyte infusions ,Minimal residual disease ,Graft-vs.-host disease ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple consolidation chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction chemotherapy and DLI. Methods Forty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction chemotherapy and DLI were eligible. The use of consolidation chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive consolidation chemotherapy and DLIs after induction chemotherapy and DLI. Results One-year cumulative incidence of relapse (CIR; 22 % 95 % confidence interval (10, 35 %) vs. 56 % (39, 73 %); P
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- 2016
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13. Monitoring of Minimal Residual Disease in Acute Lymphoblastic Leukemia
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Szczepański, Tomasz, Dawidowska, Małgorzata, Derwich, Katarzyna, Witt, Michal, editor, Dawidowska, Malgorzata, editor, and Szczepanski, Tomasz, editor
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- 2012
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14. Central nervous system involvement in childhood acute lymphoblastic leukemia is linked to upregulation of cholesterol biosynthetic pathways
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- 2022
15. Quantitative polymerase chain reaction test for molecular diagnosis of intraocular relapse of acute lymphoblastic leukemia: a case report
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Ian Yh Wong and Jennifer C H Hung
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Oncology ,medicine.medical_specialty ,business.industry ,Lymphoblastic Leukemia ,Ocular infiltration ,law.invention ,Real-time polymerase chain reaction ,Leukemia relapse ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Molecular diagnostic techniques ,business ,Polymerase chain reaction - Abstract
Leukemia relapse rarely presents with ophthalmic manifestations. We report on a 62-year-old woman with relapse of Philadelphia chromosome–positive acute lymphoblastic leukemia who presented with ocular infiltration as the sole presentation. The diagnostic difficulties are also discussed.
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- 2021
16. Reduced leukemia relapse through cytomegalovirus reactivation in killer cell immunoglobulin-like receptor-ligand-mismatched cord blood transplantation
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Makoto Onizuka, Hideki Nakasone, Tatsuo Ichinohe, Junya Kanda, Yoshiko Atsuta, Takafumi Kimura, Yoshinobu Kanda, Yuta Kawahara, Yuma Noguchi, Shuichi Ota, Satoko Morishima, Satoshi Takahashi, Takanori Ohta, Yukiyasu Ozawa, Hisayuki Yokoyama, Naoyuki Uchida, Yuna Katsuoka, and Masatsugu Tanaka
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Transplantation ,business.industry ,Hazard ratio ,Cell ,Hematopoietic Stem Cell Transplantation ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Graft vs Host Disease ,Myeloid leukemia ,Hematology ,Ligands ,medicine.disease ,medicine.anatomical_structure ,Receptors, KIR ,Leukemia relapse ,Recurrence ,Immunology ,medicine ,Humans ,Cord Blood Stem Cell Transplantation ,Killer-Cell Immunoglobulin-Like Receptor Ligand ,Receptor ,business ,Cord blood transplantation - Abstract
Cytomegalovirus (CMV) reactivation in cord blood transplantation (CBT) may result in the proliferation and maturation of natural killer (NK) cells. Similarly, a mismatch of the killer cell immunoglobulin-like receptor (KIR)-ligand induces NK cell activation. Therefore, if CMV reactivation occurs in the presence of KIR-ligand mismatch, it might improve CBT outcomes. We assessed the difference in the effect of CMV reactivation in the presence of KIR-ligand mismatch on disease relapse in the graft-versus-host direction. A total of 2840 patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and chronic myeloid leukemia were analyzed. Among those with a HLA-Bw4/A3/A11 (KIR3DL-ligand) mismatch, CMV reactivation up to 100 days following CBT had a favorable impact on relapse (18.9% vs. 32.9%, P = 0.0149). However, this effect was not observed in cases without the KIR3DL-ligand mismatch or in those with or without a HLA-C1/C2 (KIR2DL-ligand) mismatch. The multivariate analysis suggested that CMV reactivation had a favorable effect on relapse only in cases with a KIR3DL-ligand mismatch (hazard ratio 0.54, P = 0.032). Moreover, the interaction effect between CMV reactivation and KIR3DL-ligand mismatch on relapse was significant (P = 0.039). Thus, our study reveals the association between KIR-ligand mismatches and CMV reactivation, which will enhance CBT outcomes.
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- 2021
17. Prophylactic Donor Lymphocyte Infusion (DLI) Followed by Minimal Residual Disease and Graft-versus-Host Disease–Guided Multiple DLIs Could Improve Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Refractory/Relapsed Acute Leukemia
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Yan, Chen-Hua, Liu, Qi-fa, Wu, De-pei, Zhang, Xi, Xu, Lan-Ping, Zhang, Xiao-hui, Wang, Yu, Huang, He, Bai, Hai, Huang, Fen, Ma, Xiao, and Huang, Xiao-Jun
- Subjects
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HEMATOPOIETIC stem cell transplantation , *ACUTE leukemia , *DISEASE relapse , *GRAFT versus host disease , *HEALTH outcome assessment , *LEUKEMIA treatment , *THERAPEUTICS - Abstract
Patients with refractory/relapsed acute leukemia who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT) are still at a high risk for relapse post-transplant. To investigate the impact of prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease (MRD) test and graft - versus-host disease (GVHD)–guided multiple DLIs to prevent relapse and improve survival in patients with refractory/relapsed acute leukemia who received allo-HSCT. A multicenter prospective study was designed. In total, 100 patients who achieved complete remission at 30 days post-transplant and had no uncontrolled infection, organ failure, or active GVHD were eligible First, prophylactic DLI was administered at 30 days after HLA-matched related HSCT or 45 to 60 days after HLA-matched unrelated HSCT or haploidentical HSCT. Subsequently, multiple DLIs were administered based on the results of MRD test and whether they developed GVHD. In addition to DLI, chemotherapy was also given to patients who had a positive MRD test. Three-year cumulative incidence of relapse, leukemia-free survival, and survival post-transplant were 32.4% (95% confidence interval, 22.4% to 42.4%), 50.3% (95% confidence interval, 40.3% to 60.3%), and 51.4% (95% confidence interval, 41.2% to 61.6%), respectively. In multivariate analysis, a positive MRD test (HR, 3.840; 95% confidence interval, 1.678 to 5.784; P = .001) and receiving 1 course of DLI (HR, 4.346; 95% confidence interval, 1.223 to 9.450, P = .023) were associated with an increased relapse risks. These data suggest that prophylactic DLI followed by MRD test and GVHD-guided multiple DLIs reduced relapse and increased survival post-transplant in patients with refractory/relapsed acute leukemia who received allo-HSCT. The study is registered at www.ClinicalTrials.gov as NCT01455272. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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18. Breathing adapted radiation therapy for leukemia relapse in the breast: A case report
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Selcuk Demiral, Onurhan Colak, Fatih Ozcan, Bahar Dirican, Murat Beyzadeoglu, Ferrat Dincoglan, Hakan Gamsiz, Yelda Elcim, Bora Uysal, and Omer Sager
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0301 basic medicine ,medicine.medical_specialty ,Both breasts ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Breast relapse ,Breathing adapted radiation therapy ,03 medical and health sciences ,Active breathing control ,0302 clinical medicine ,Whole Breast Irradiation ,Leukemia relapse ,Case report ,medicine ,Severe pain ,skin and connective tissue diseases ,Leukemic Infiltration ,business.industry ,medicine.disease ,Radiation therapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Radiology ,business ,Infiltration (medical) ,T-cell acute lymphoblastic leukemia - Abstract
Background Infiltration of the breast by leukemic cells is uncommon but may manifest as an oncological emergency requiring prompt management. Extramedullary relapse of T-cell acute lymphoblastic leukemia (T-ALL) within the breast is exceedingly rare and there is paucity of data in the literature regarding this entity. No consensus exists on management of isolated extramedullary breast relapses of T-ALL. Herein, we report a case of isolated extramedullary breast relapse of T-ALL treated with breathing adapted radiation therapy (BART) using the active breathing control (ABC) system. Case summary The patient was a 33-year-old female with diagnosis of T-ALL. She received intensive systemic chemotherapy that resulted in complete remission of her disease, and then underwent allogeneic hematopoietic stem cell transplantation. After a 15 mo period without symptoms and signs of progression, the patient presented with palpable masses in both breasts. She complained from severe pain and swelling of the breasts. Imaging workup showed bilateral breast lesions, and diagnosis of breast infiltration by leukemic cells was confirmed after immunohistopathological evaluation. The patient suffering from severe pain, discomfort, and swelling of both breasts due to leukemic infiltration was referred to the Radiation Oncology Department for symptomatic palliation. Whole breast irradiation was delivered to both breasts of the patient with BART using the ABC system. The patient had complete resolution of her symptoms after treatment with BART. Conclusion BART with the ABC system resulted in complete resolution of the patient's symptoms due to leukemic infiltration of both breasts with T-ALL. This contemporary treatment technique should be preferred for radiotherapeutic management of patients with leukemic infiltration of the breasts to achieve effective symptomatic palliation.
- Published
- 2019
19. Double trouble or a silver lining? A case report of two patients with NPM1-mutated donor-derived acute myeloid leukemia (AML).
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- 2021
20. Double trouble or a silver lining? A case report of two patients with NPM1-mutated donor-derived acute myeloid leukemia (AML).
- Published
- 2021
21. Construction of a solid Cox model for AML patients based on multiomics bioinformatic analysis
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Yi Su, Jia Liu, Fu Li, Xi Zhang, Jiao Cai, Lei Gao, and Shi-cang Yu
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Cancer Research ,Cell type ,Proportional hazards model ,Myeloid leukemia ,Drug resistance ,Computational biology ,Biology ,medicine.anatomical_structure ,Immune system ,Oncology ,Leukemia relapse ,medicine ,Bone marrow ,Gene - Abstract
Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. The bone marrow (BM) microenvironment in AML plays an important role in leukemogenesis, drug resistance and leukemia relapse. In this study, we aimed to identify reliable immune-related biomarkers for AML prognosis by multiomics analysis. We obtained expression profiles from The Cancer Genome Atlas (TCGA) database and constructed a LASSO-Cox regression model to predict the prognosis of AML using multiomics bioinformatic analysis data. This was followed by independent validation of the model in the GSE106291 (n=251), GSE12417 (n=163) and GSE37642 (n=137) datasets and mutated genes in clinical samples for predicting overall survival (OS). Molecular docking was performed to predict the most optimal ligands to these hub genes. The single-cell RNA sequence dataset GSE116256 was used to clarify the expression of the hub genes in different immune cell types. According to their significant differences in immune gene signatures and survival trends, we concluded that the immune infiltration-lacking subtype (IL type) is associated with better prognosis than the immune infiltration-rich subtype (IR type). Using the LASSO model, we built a classifier based on 5 hub genes to predict the prognosis of AML (risk score = −0.086×ADAMTS3 + 0.180×CD52 + 0.472×CLCN5 - 0.356×HAL + 0.368×ICAM3). In summary, we constructed a prognostic model of AML using integrated multiomics bioinformatic analysis that could serve as a therapeutic classifier.
- Published
- 2021
22. Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready?
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Boyiadzis, Michael and Whiteside, Theresa L.
- Abstract
The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients’ plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML. The rationale for developing exosome-based methodology for minimal residual disease detection is based on promising early observations. However, standards need to be established for evaluating exosome identity, isolation from body fluids, and assessment methods. The rapidly expanding knowledge of the exosome biology suggests that the exosome status as potential biomarkers may become clarified in the near future. [ABSTRACT FROM PUBLISHER]
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- 2016
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23. Genetic Mechanism of Leukemia Relapse Following CD19 Chimeric Antigen Receptor T Cell Therapy
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Fapohunda Funmilayo Omotoyosi, Shenyan Shi, Songlin Qiu, Ye Pan, Keping Chen, Zhigang Guo, and Peng Lü
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Oncology ,Cart ,Cancer Research ,medicine.medical_specialty ,Antigens, CD19 ,Cell- and Tissue-Based Therapy ,Receptors, Antigen, T-Cell ,Immunotherapy, Adoptive ,CD19 ,Leukemia relapse ,immune system diseases ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Pharmacology ,Receptors, Chimeric Antigen ,biology ,Mechanism (biology) ,business.industry ,hemic and immune systems ,General Medicine ,B-cell acute lymphoblastic leukemia ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Lymphoma ,Leukemia ,biology.protein ,Chimeric Antigen Receptor T-Cell Therapy ,business - Abstract
Chimeric antigen receptor T cell therapy (CART) has achieved excellent results in the past 10 years for treating of leukemia. Treatment of B cell acute lymphoblastic leukemia by anti-CD19 CART can reach a complete remission rate of 90%. Although CART has greatly improved the treatment of patients with leukemia and lymphoma, as many as one-third of the patients can suffer disease relapse after CART. The tumor surface marker CD19 is negative in most the patients who relapse, and these patients display high expression of CD19 before treatment. In this review, the current causes of CD19-negative relapses after CD19 CART against leukemia, and the mechanisms of target escape are briefly summarized. Also, methods and strategies for treating relapse to provide references for the treatment of leukemia relapse are also discussed.
- Published
- 2021
24. Post-Irradiation Hyperamylasemia Is a Prognostic Marker for Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Pediatric Population: A Retrospective Single-Centre Cohort Analysis
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Davide Zanon, Francesco Baldo, Francesca Ciriello, Annalisa Marcuzzi, Roberto Simeone, Antonio Giacomo Grasso, Rossella Vidimari, Natalia Maximova, Alessandra Maestro, Egidio Barbi, Baldo, Francesco, Simeone, Roberto, Marcuzzi, Annalisa, Grasso, Antonio Giacomo, Vidimari, Rossella, Ciriello, Francesca, Zanon, Davide, Maestro, Alessandra, Barbi, Egidio, and Maximova, Natalia
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medicine.medical_specialty ,proinflammatory cytokine ,medicine.medical_treatment ,overall survival ,Hematopoietic stem cell transplantation ,hematopoietic stem cell transplantation ,leukemia relapse ,pediatric patients ,proinflammatory cytokines ,total amylase ,total body irradiation ,Gastroenterology ,Article ,NO ,Internal medicine ,medicine ,business.industry ,Mortality rate ,General Medicine ,Total body irradiation ,Transplantation ,Regimen ,Toxicity ,Hyperamylasemia ,Medicine ,business ,pediatric patient ,Cohort study - Abstract
Background: Total body irradiation (TBI) is a mandatory step for patients with acute lymphoblastic leukemia (ALL), undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In the past, amylases have been reported to be a possible sign of TBI toxicity. We investigated the relationship between total amylases (TA) and transplant-related outcomes in pediatric recipients. Methods: We retrospectively analyzed the medical records of all the patients who underwent allogeneic HSCT between January 2000 and November 2019. The inclusion criteria were the following: recipient’s age between 2 and 18, diagnosis of ALL, no previous transplantation, and use of TBI-based conditioning. The serum total amylase and pancreatic amylase were evaluated before, during, and after transplantation. Cytokines and chemokines assays were retrospectively performed. Results: 78 patients fulfilled the inclusion criteria. Fifty-seven patients were treated with fractionated TBI, and 21 with a single-dose regimen. The overall survival (OS) was 62.8%. Elevated values of TA were detected in 71 patients (91%). The TA were excellent in predicting the OS (AUC = 0.773, 95% CI = 0.66–0.86, p <, 0.001). TA values below 374 U/L were correlated with a higher OS. The highest mean TA values (673 U/L) were associated with a high disease-progression mortality rate. The TA showed a high predictive performance for disease progression-related death (AUC = 0.865, 95% CI = 0.77–0.93, 0.0001). Elevated TA values were also connected with significantly higher levels of proinflammatory cytokines, such as TNF-α, IL-6, and RANTES (p <, 0.001). Conclusions: this study shows that TA is a valuable predictor of post-transplant OS and increased risk of leukemia relapse.
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- 2021
25. A real-life Turkish experience of venetoclax treatment in high-risk myelodysplastic syndrome and acute myeloid leukemia
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Aliihsan Gemici, Senem Maral, Fahir Özkalemkaş, Huseyin Saffet Bekoz, Eren Gunduz, Rafet Eren, Mehmet Hilmi Dogu, İbrahim Ethem Pinar, Istemi Serin, Ahmet Kursad Gunes, Gulsum Akgun Cagliyan, Volkan Karakuş, Inci Alacacioglu, Fatma Deniz Sargın, Atakan Tekinalp, Idris Ince, Ömür Gökmen Sevindik, Tekin Guney, Ayfer Gedük, İstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, and Dogu, Mehmet Hilmi
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blood toxicity ,Male ,Cancer Research ,drug safety ,Turkey ,very elderly ,diarrhea ,high risk patient ,Turkey (republic) ,granulocyte colony stimulating factor ,low drug dose ,chemistry.chemical_compound ,0302 clinical medicine ,cytarabine ,de novo acute myeloid leukemia ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Flt3 ligand ,antineoplastic agent ,Aged, 80 and over ,Sulfonamides ,Hematology ,DNA methyltransferase 3A ,tumor biopsy ,Remission Induction ,leukemia relapse ,Myeloid leukemia ,Middle Aged ,cohort analysis ,Granulocyte colony-stimulating factor ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Oncology ,monotherapy ,030220 oncology & carcinogenesis ,Cohort ,secondary acute myeloid leukemia ,Female ,nucleophosmin ,intermediate risk patient ,medicine.drug ,Adult ,Acute Myeloid Leukemia ,azacitidine ,medicine.medical_specialty ,Bcl2 ,Inhibitor ,incomplete hematological recovery ,overall survival ,adverse drug reaction ,Antineoplastic Agents ,Article ,high throughput sequencing ,skin manifestation ,Venetoclax ,morphological leukemia free state ,03 medical and health sciences ,remission ,turkey (bird) ,Internal medicine ,sulfonamide ,cancer combination chemotherapy ,oncological parameters ,pneumonia ,Humans ,human ,Aged ,business.industry ,fused heterocyclic rings ,sex ratio ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,major clinical study ,mortality ,Survival Analysis ,human tissue ,myelodysplastic syndrome ,Lymphoma ,disease assessment ,drug efficacy ,karyotype ,Pneumonia ,Real Life ,multicenter study ,chemistry ,Myelodysplastic Syndromes ,Cytarabine ,fatigue ,Common Terminology Criteria for Adverse Events ,business ,decitabine ,030215 immunology - Abstract
Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). A total of 60 patients with a median age of 67 years from different centers were included in the final analysis. Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML. Introduction: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. Materials and Methods: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. Results: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. Conclusion: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML.
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- 2021
26. Outcomes of Patients With Acute Myeloid Leukemia Who Relapse After 5 Years of Complete Remission
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Mounzer Agha, Robert L. Redner, Arisha Patel, Konstantinos Lontos, Michael Boyiadzis, Annie Im, Melissa Saul, Rafic Farah, Jing-Zhou Hou, Anastasios Raptis, Alison R. Sehgal, Daniel P. Normolle, James M. Rossetti, and Kathleen A. Dorritie
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Time Factors ,Adolescent ,Survival ,Decitabine ,Brief Communication ,Prognostic factors ,Cohort Studies ,Young Adult ,Leukemia relapse ,Maintenance therapy ,Recurrence ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Acute myeloid leukemia (AML) ,Humans ,Transplantation, Homologous ,In patient ,Aged ,Retrospective Studies ,business.industry ,Remission Induction ,Complete remission ,Myeloid leukemia ,Induction chemotherapy ,General Medicine ,Late relapse ,Middle Aged ,Prognosis ,Confidence interval ,Survival Rate ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Oncology ,Cohort ,Female ,Neoplasm Recurrence, Local ,business - Abstract
Leukemia relapse 5 years after achieving first complete remission (CR1) is uncommon in patients with acute myeloid leukemia (AML). In this study, we evaluated the outcomes of AML patients with late relapse at our institution and reviewed the literature for these patients. The study cohort consisted of nine AML patients with late relapse. The median interval between CR1 and AML relapse was 6.1 years (range: 5.116.2 years). At relapse, the karyotype was different from the initial AML diagnosis in 50% of patients. At the time of AML relapse, seven patients received induction chemotherapy and two patients received hypomethylating agents with an overall CR rate of 66%. The median time to relapse after achieving second CR (CR2) was 16.5 months [95% confidence interval (CI): 9.4, NA]. The median overall survival after first relapse was 28.6 months (95% CI: 7.3, 3.466.5 months). Despite initial CR after reinduction therapy, relapse rates are still high, suggesting that alternative strategies for postremission therapies are warranted in CR2. These approaches include the use of allogeneic hematogenic cell transplantation and the use of newly approved AML agents as maintenance therapy in nontransplant eligible patients.
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- 2020
27. Measurable residual disease of acute lymphoblastic leukemia in allograft settings: how to evaluate and intervene
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Si-Qi Li, Yu-Qian Sun, Ying-Jun Chang, and Xiao-Su Zhao
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Lymphoblastic Leukemia ,Disease ,Hematopoietic stem cell transplantation ,Flow cytometry ,Donor Selection ,03 medical and health sciences ,0302 clinical medicine ,Leukemia relapse ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Transplantation, Homologous ,Pharmacology (medical) ,Haploidentical transplantation ,medicine.diagnostic_test ,business.industry ,Hematopoietic Stem Cell Transplantation ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Allografts ,surgical procedures, operative ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,business - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curable strategy for acute lymphoblastic leukemia (ALL), especially for adult cases. However, leukemia relapse after allograft restricts the improvement of transplant outcomes. Measurable residual disease (MRD) has been the strongest predictor for relapse after allo-HSCT, allowing MRD-directed preemptive therapy.This manuscript summarizes the detection of MRD in patients with ALL who undergo allo-HSCT, focusing the effects of positive pre-HSCT MRD and post-HSCT MRD on outcomes as well as MRD-directed interventions.Except for MFC and RQ-PCR, other strategies, such as next-generation sequencing and RNAseq, have been developed for MRD determination. Negative effects of positive MRD peri-transplantation on outcomes of ALL patients were observed both in human leukocyte antigen (HLA)-matched sibling donor transplantation and in alternative donor transplantation. Advances have been made in determining the need for transplant according to MRD evaluation after induction or consolidation therapy. A number of approaches, including CAR-T-cell therapy, antibodies (blinatumomab, etc), targeted therapy (imatinib, etc), transplant donor selection, as well as donor lymphocyte infusion and interferon-α, have been successfully used or are promising for peri-transplantation MRD interventions. This progress could lead to the significant improvement of transplant outcomes for ALL patients.
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- 2020
28. Tongue Mass Arising after Hematopoietic Cell Transplantation and Leukemia Relapse
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Eunae Sandra Cho, Hyun Sil Kim, Slmaro Park, and Sung Hwan Choi
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Transplantation ,Oncology ,medicine.medical_specialty ,Hematopoietic cell ,Leukemia relapse ,business.industry ,Internal medicine ,Tongue mass ,Medicine ,business - Published
- 2018
29. A unique case of donor cell myeloma
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Virginia Reyes-Nuñez, María Fernanda Vallejo-Villalobos, Alejandro Ruiz-Argüelles, Guillermo J. Ruiz-Argüelles, Gisela B. Gomez-Cruz, and Solón Javier Garcés-Eisele
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Cancer Research ,Donor cell ,business.industry ,medicine.medical_treatment ,Hematology ,Hematopoietic stem cell transplantation ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Leukemia relapse ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Donor cell leukemia ,Cancer research ,medicine ,business ,030215 immunology - Abstract
Leukemia relapse occurring in donor cells, so called donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation has been previously reported [1–3]. Some authors have suggest...
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- 2019
30. Engraftment Kinetics and Recipient Chimerism Increase to Predict Leukemia Relapse By Ptcy and Non-Ptcy Transplant
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Shin Mineishi, Brooke Silar, Seema Naik, Joseph Mierski, Witold B. Rybka, W. Christopher Ehmann, Ruoheng Zhang, Hiroko Shike, Hong Zheng, Baldeep Wirk, Shouhao Zhou, David F. Claxton, Jason Liao, Valerie I. Brown, Kevin Rakszawski, Kentaro Minagawa, Gina Mackey, Robert J. Greiner, and Myles Nickolich
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Oncology ,medicine.medical_specialty ,Leukemia relapse ,business.industry ,Internal medicine ,Immunology ,medicine ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
Recipient chimerism increase has been used to predict leukemia relapse in post-hematopoietic cell transplant (HCT) patients with conventional GVHD prophylaxis. However, the value of recipient chimerism increase in patients with post-transplant cyclophosphamide (PTCy) is not clear. We compared PTCy to conventional GVHD prophylaxis (non-PTCy) patients regarding engraftment kinetics and the clinical significance of the 2 chimerism parameters, increasing mixed chimerism (IMC) and degree of recipient chimerism increase at the first event (Δ increase). We studied both total and T-cell-specific chimerism. While leukemia relapse is manifested by an increase in total cell recipient chimerism, an increase in T-cell-specific recipient chimerism may be more impactful in predicting relapse because of the effect of increased T-cell-specific chimerism on the graft-versus-leukemia effect. A total of 220 patients (PTCy: 44, non-PTCy: 176) with AML, MDS, and ALL underwent HCT at our institution from January 2014 to September 2020 and were included in this study (Table). Chimerism was tested at least monthly for the first 3 months, followed by every 3 months up until 1-year post-HCT, and then every 6-12 months thereafter. Short tandem repeat or quantitative PCR were used when percent recipient chimerism was ≥5% and PTCy patients achieved complete donor chimerism (CC) in total cells earlier at a deeper level (>99%) as compared to non-PTCy patients. Deeper total cell CC (>99%) was achieved in 79.5% of PTCy vs. 51% of non-PTCy patients at day 250, while CC (>95%) was achieved in almost 90% of patients in both groups within 100 days (Figure 1A and B). In comparison, the percentage of PTCy patients achieving T-cell-specific CC was significantly higher at day 250 post-HCT: CC (>95%/>99%) was 79.7%/68.4% in PTCy patients vs. 56.1%/37.5% in non-PTCy patients (Figure 1C and D). To evaluate their impact in predicting relapse, IMC was stratified into no IMC, 1 IMC (≥1 nonconsecutive IMC), and 2 IMC (≥2 consecutive IMC), and degree of recipient chimerism increase at the first event (Δ increase) was stratified into Two IMC (total), 1 IMC (T-cell), and 2 IMC (T-cell) groups were associated with shorter DFS in non-PTCy patients but not in PTCy patients (Figure 2). One and 2 IMC groups (both total and T-cell) were associated with relapse risk in non-PTCy patients. Furthermore, 1 IMC (T-cell) in non-PTCy patients showed a strong association in relapse risk (HR 7.0 (95%CI 2.83-17.8) p Δ increase ≥1% (total and T-cell) and Δ increase ≥0.1% (T-cell) were associated with shorter DFS in non-PTCy patients, while only Δ increase ≥1% (T-cell) only showed a trend towards shorter DFS in PTCy patients (Figure 3). The Cox regression model showed Δ increase ≥1% in both total, and T-cell chimerism was associated with relapse risk in non-PTCy patients (HR 6.4 (95%CI 2.9-14.2) p This is one of the most extensive studies investigating engraftment kinetics and the association of total and T-cell recipient chimerism increase to predict leukemia relapse in PTCy and non-PTCy HCT recipients. We found that PTCy HCT recipients achieved deeper engraftment earlier as compared to non-PTCy recipients. In addition, the two chimerism parameters (IMC and Δ increase) are less reliable in predicting relapse in PTCy than non-PTCy recipients. However, other factors, such as disease type, conditioning regimen, and donor HLA disparity, may have affected engraftment kinetics and the significance of chimerism parameters. Further investigations are warranted to elucidate the impact of the engraftment kinetics and recipient chimerism increase to predict relapse, especially in the PTCy setting. Figure 1 Figure 1. Disclosures Rakszawski: SeaGen: Speakers Bureau. Naik: Takeda: Other: Virtual Advisory Board Member ; Sanofi: Other: Virtual Advisory Board Member ; Kite: Other: Virtual Advisory Board Member. Rybka: Spark Therapeutics: Consultancy; Merck: Consultancy. Claxton: Astellas: Other: Clinical Trial; Novartis: Research Funding; Astex: Research Funding; Cyclacel: Research Funding; Daiichi Sankyo: Research Funding; Incyte: Research Funding.
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- 2021
31. Significance of Ethnicity in the Risk of Acute Graft-versus-Host Disease and Leukemia Relapse after Unrelated Donor Hematopoietic Stem Cell Transplantation.
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Morishima, Yasuo, Kawase, Takakazu, Malkki, Mari, Morishima, Satoko, Spellman, Stephen, Kashiwase, Koichi, Kato, Shunichi, Cesbron, Anne, Tiercy, Jean-Marie, Senitzer, David, Velardi, Andrea, and Petersdorf, Effie W.
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ETHNICITY , *HEMATOPOIETIC stem cell transplantation , *DISEASE risk factors , *GRAFT versus host disease , *ACUTE leukemia , *DISEASE relapse , *ORGAN donors - Abstract
Abstract: The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient–donor pairs from the International Histocompatibility Working Group in HCT met the following 3 criteria: (1) HLA-A, -B, -C, -DRB1, and -DQB1 allele matched donor, (2) diagnosis of leukemia, and (3) non–T cell depleted GVHD prophylaxis. Posttransplantation risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, white, African American, Hispanic, and Native American patients that underwent transplantation from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II to IV and 15.3% grades III to IV; non-Japanese Asian patients: 42.1% grades II to IV and 15.7% grades III to IV) compared with white patients (56.5% grades II to IV and 22.6% grades III to IV) (P < .001). The hazard ratio of acute GVHD for white patients was significantly higher than for Japanese patients. Unexpectedly, the hazard ratio of leukemia relapse in white patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background. [Copyright &y& Elsevier]
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- 2013
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32. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT
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Piemontese, Simona, Boumendil, Ariane, Labopin, Myriam, Schmid, Christoph, Ciceri, Fabio, Arcese, William, Koc, Yener, Gulbas, Zafar, Tischer, Johanna, Bruno, Benedetto, Wu, Depei, Blaise, Didier, Beelen, Dietrich, Irrera, Giuseppe, Ruggeri, Annalisa, Houhou, Mohamed, Mohty, Mohamad, Nagler, Arnon, and on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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- 2019
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33. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL.
- Abstract
Zanubrutinib is a potent and highly selective inhibitor of Bruton tyrosine kinase (BTK). In this first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (3 1 3 dose escalation) had relapsed/refractory B-cell malignancies and received zanubrutinib 40, 80, 160, or 320 mg once daily or 160 mg twice daily. Part 2 (expansion) consisted of disease-specific cohorts, including treatment-naive or relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL). The primary end points were safety and tolerability, and definition of the maximum tolerated dose (part 1). Additional end points included pharmacokinetics/pharmacodynamics and preliminary efficacy. Reported herein are results from 144 patients enrolled in the dose-finding and CLL/SLL cohorts. No dose-limiting toxicities occurred in dose escalation. Median BTK occupancy in peripheral blood mononuclear cells was >95% at all doses. Sustained complete (>95%) BTK occupancy in lymph node biopsy specimens was more frequent with 160 mg twice daily than 320 mg once daily (89% vs 50%; P 5 .0342). Consequently, 160 mg twice daily was selected for further investigation. With median follow-up of 13.7 months (range, 0.4-30.5 months), 89 CLL/SLL patients (94.7%) remain on study. Most toxicities were grade 1/2; neutropenia was the only grade 3/4 toxicity observed in >2 patients. One patient experienced a grade 3 subcutaneous hemorrhage. Among 78 efficacy-evaluable CLL/SLL patients, the overall response rate was 96.2% (95% confidence interval, 89.2-99.2). Estimated progression-free survival at 12 months was 100%. Zanubrutinib demonstrated encouraging activity in CLL/SLL patients, with a low incidence of major toxicities.Copyright © 2019 by The American Society of Hematology
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- 2019
34. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL.
- Abstract
Zanubrutinib is a potent and highly selective inhibitor of Bruton tyrosine kinase (BTK). In this first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (3 1 3 dose escalation) had relapsed/refractory B-cell malignancies and received zanubrutinib 40, 80, 160, or 320 mg once daily or 160 mg twice daily. Part 2 (expansion) consisted of disease-specific cohorts, including treatment-naive or relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL). The primary end points were safety and tolerability, and definition of the maximum tolerated dose (part 1). Additional end points included pharmacokinetics/pharmacodynamics and preliminary efficacy. Reported herein are results from 144 patients enrolled in the dose-finding and CLL/SLL cohorts. No dose-limiting toxicities occurred in dose escalation. Median BTK occupancy in peripheral blood mononuclear cells was >95% at all doses. Sustained complete (>95%) BTK occupancy in lymph node biopsy specimens was more frequent with 160 mg twice daily than 320 mg once daily (89% vs 50%; P 5 .0342). Consequently, 160 mg twice daily was selected for further investigation. With median follow-up of 13.7 months (range, 0.4-30.5 months), 89 CLL/SLL patients (94.7%) remain on study. Most toxicities were grade 1/2; neutropenia was the only grade 3/4 toxicity observed in >2 patients. One patient experienced a grade 3 subcutaneous hemorrhage. Among 78 efficacy-evaluable CLL/SLL patients, the overall response rate was 96.2% (95% confidence interval, 89.2-99.2). Estimated progression-free survival at 12 months was 100%. Zanubrutinib demonstrated encouraging activity in CLL/SLL patients, with a low incidence of major toxicities.Copyright © 2019 by The American Society of Hematology
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- 2019
35. Isolated extramedullary relapse of acute lymphoblastic leukemia in the breast of an adolescent girl: radiologic findings and discussion.
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Kumar, Prasanna R. G., Grossman, Zachary, Scorza, Lari, Khoury, Thaer, and Nayyar, Rahul
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CASE studies , *B cell lymphoma , *HEMATOMA , *CANCER relapse , *DRUG therapy , *DIAGNOSIS - Abstract
We report a case of isolated extramedullary leukemia relapse in the breast of an adolescent girl. A 13-year-old girl with acute lymphoblastic leukemia in remission, post-chemotherapy and unrelated cord blood transplant, presented with a breast lump. US and mammography demonstrated a large hypervascular heterogeneous mass. Examination of tissue provided by US-guided core biopsy confirmed focal leukemic relapse. US is a commonly used diagnostic tool in children and adolescents with a breast mass, for both characterization and guided biopsy. [ABSTRACT FROM AUTHOR]
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- 2010
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36. Which Role for Rituximab in Hairy Cell Leukemia? Reflections on Six Cases.
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Malfuson, J. V., Fagot, T., Konopacki, J., Souleau, B., Cremades, S., and De Revel, T.
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HAIRY cell leukemia , *INTERFERONS , *PURINES , *B cells , *LYMPHOPROLIFERATIVE disorders , *NEUTROPENIA - Abstract
Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative disorder. Treatment has been revolutionized by the advent of interferon (IFN)-α and purine analogs (PA). First-line therapy with PA yields complete response rates of 75–100%, with many long-lasting remissions. In the event of profound neutropenia and/or infectious complications, a short sequence of IFN-α may precede PA treatment. Because of the excellent results achieved with PA therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that is highly effective against most B-cell lymphomas) in HCL has yet to be elucidated. Six HCL cases treated with rituximab are reported herein with a view to elucidating the potential role of the drug in HCL. The indications essentially consist of relapsing or refractory disease, avoiding the cumulative toxicity of PA, consolidation therapy in order to eradicate minimal residual disease, and first-line therapy for patients with contraindications to PA and IFN-α. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2010
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37. Comparable Outcome of Alternative Donor and Matched Sibling Donor Hematopoietic Stem Cell Transplant for Children with Acute Lymphoblastic Leukemia in First or Second Remission Using Alemtuzumab in a Myeloablative Conditioning Regimen
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Kennedy-Nasser, Alana A., Bollard, Catherine M., Myers, G. Doug, Leung, Kathryn S., Gottschalk, Stephen, Zhang, Yiqun, Liu, Hao, Heslop, Helen E., Brenner, Malcolm K., and Krance, Robert A.
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STEM cells , *CELLULAR therapy , *CELL transplantation , *LYMPHOCYTIC leukemia - Abstract
HLA-matched sibling donor (MSD) stem cell transplantation can cure >60% of pediatric patients with acute lymphoblastic leukemia (ALL), but <30% of patients will have a sibling donor. Alternative donor (AD) transplantation can be curative but has a higher risk of graft-versus-host disease (GVHD). The addition of alemtuzumab (Campath 1-H) to AD transplants produces in vivo T cell depletion, which may reduce the risk for GVHD. We now report the outcome for 83 children with ALL (41 MSD, 42 AD) undergoing stem cell transplantation in first or second complete remission. All patients received myeloablative conditioning, including cyclophosphamide, cytarabine arabinoside, and total-body irradiation, with alemtuzumab administered to AD recipients. GVHD prophylaxis consisted of a calcineurin inhibitor with either short-course methotrexate or prednisone. Disease-free survival (DFS) for MSD recipients was 72.3% (95% confidence interval [CI], 55.4%-83.6%) versus 62.4% (95% CI, 45.2%-75.4%) for AD recipients. The 100-day mortality was 7.1% in the AD group and 2.4% in the MSD group. Relapse rates were identical (24%). Treatment-related mortality, principally viral infection, explained the difference in survival. For children undergoing stem cell transplantation (SCT) from alternative donors, alemtuzumab with a myeloablative conditioning regimen resulted in DFS comparable to MSD. [Copyright &y& Elsevier]
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- 2008
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38. Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression.
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Guogen Mao, Fenghua Yuan, Absher, Kimberly, Jennings, C. Darrell, Howard, Dianna S., Jordan, Craig T., and Gu, Liya
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ACUTE leukemia ,HEMATOLOGICAL manifestations of general diseases ,HEMATOLOGICAL oncology ,BLOOD diseases ,DNA damage ,MUTAGENESIS ,CARCINOGENESIS - Abstract
Acute myeloid leukemia (AML) is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.Cell Research (2008) 18:281–289. doi: 10.1038/cr.2008.14; published online 29 January 2008 [ABSTRACT FROM AUTHOR]
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- 2008
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39. Increased frequencies of CD4+CD25high Tregs correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
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Nadal, E., Garin, M., Kaeda, J., Apperley, J., Lechler, R., and Dazzi, F.
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TREATMENT of chronic myeloid leukemia , *HEMATOPOIETIC stem cell transplantation , *HOMOGRAFTS , *T cells , *GRAFT rejection - Abstract
The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4+CD25high regulatory T cells (Tregs) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4+CD25high Tregs in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of Tregs in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the Tregs purified from SCT patients exhibited a more potent suppressive activity than Tregs isolated from healthy volunteers. Patients in whom Tregs numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in Tregs might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that Tregs exert an inhibitory effect on GvL.Leukemia (2007) 21, 472–479. doi:10.1038/sj.leu.2404522; published online 18 January 2007 [ABSTRACT FROM AUTHOR]
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- 2007
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40. Second Allogeneic Bone Marrow Transplantation after Myeloablative Conditioning Analysis of 43 Cases from Single Institution.
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Al-qurashi, F., Ayas, M., Al Sharif, F., Ibrahim, F., Sahovic, F., Al Mahr, M., Chaudhri, N., Mohareb, R. Al, Zahrani, H. Al, Jffri, A. Al, Omar, H. Al, Shanqeeti, A. Al, Sfth, P., Aslam, M., Solh, H. Fl, and Aljurf, M.
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BONE marrow transplantation , *GRAFT versus host disease , *HEMATOPOIETIC system , *BONE marrow , *GRAFT versus host reaction , *IMMUNOLOGIC diseases - Abstract
Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT 1 ), median age was 11.5 years (range, 0.16-45 years). BMT 1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, β-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT 1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT 2 ) was 14 years (range, 0.41-46.7 years). Indications for BMT 2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT 1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT 1 to BMT 2 interval was 13 months (range, 1-107 months). For BMT 2 , the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT 1 and chemotherapy conditioning±ATG for those who received radiation containing conditioning at BMT 1 . Bone marrow was the stem cell source for all patients at BMT 2 and all except three autologous peripheral stem cell transplantation patient at BMT 1 . Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT 2 . At a median follow up of 36 months after BMT 2 , 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD±9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT 1 -BMT 2 interval of ≥6 months ( P =0.0007) and age at BMT 2 ≤10 years ( P =0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant ( P =0.23). There was no statistically significant difference in survival outcome of BMT 2 using same donor vs. alternate related donor ( P =0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age ≤10 years and with an interval of ≥6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor. [ABSTRACT FROM AUTHOR]
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- 2004
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41. Abstract # 3208 Molecular correlates of socioeconomic status predict acute myelogenous leukemia relapse following hematopoietic cell transplantation
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S.R. Spellman, Jennifer M. Knight, Stephanie J. Lee, J D Rizzo, Jesusa M.G. Arevalo, Brent R. Logan, T. Wang, Steve W. Cole, N. He, and M.R. Verneris
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Oncology ,medicine.medical_specialty ,Hematopoietic cell ,Endocrine and Autonomic Systems ,business.industry ,Immunology ,Transplantation ,Behavioral Neuroscience ,Myelogenous ,Leukemia relapse ,Internal medicine ,Medicine ,business ,Socioeconomic status - Published
- 2019
42. Predicting leukemia relapse
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José I. Martín-Subero
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0301 basic medicine ,Developmental stage ,Genetic heterogeneity ,business.industry ,Cell ,General Medicine ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Precursor Cell Lymphoblastic Leukemia Lymphoma ,03 medical and health sciences ,Leukemia ,030104 developmental biology ,medicine.anatomical_structure ,Leukemia relapse ,hemic and lymphatic diseases ,medicine ,Cancer research ,Mass cytometry ,business ,B cell - Abstract
Mass cytometry of acute B cell lymphoblastic leukemias at diagnosis reveals intrapatient phenotypic heterogeneity and specific signatures that mimic cell developmental stage and predict future relapse.
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- 2018
43. Regulatory T cells in allogeneic hematopoietic stem cell transplantation: From the lab to the clinic
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Jin-Qiao Zhang, Jian-Zhu Yang, Guang Gu, and Li-Xia Sun
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0301 basic medicine ,medicine.medical_treatment ,Immunology ,Graft vs Host Disease ,chemical and pharmacologic phenomena ,Hematopoietic stem cell transplantation ,Disease ,Biology ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immune Reconstitution ,Leukemia relapse ,immune system diseases ,medicine ,Secondary Prevention ,Humans ,Leukemia ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,Adoptive Transfer ,surgical procedures, operative ,030104 developmental biology ,Graft-versus-host disease ,Hematologic Neoplasms ,Chronic gvhd ,Neoplasm Recurrence, Local ,030215 immunology - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curable strategy for the treatment of hematological malignancies and nonmalignant diseases. However, graft-versus-host disease (GVHD) and relapse are still two major causes of morbidity and mortality after allo-HSCT, and both restrict the improvement of transplant outcomes. Regulatory T cells (Tregs) has been successfully used in allo-SCT settings. In this review, we summarize recent advances in experimental studies that have evaluated the roles played by Tregs in the establishment of novel transplant modalities, the prevention of GVHD and the enhancement of immune reconstitution. We also discuss the application of Tregs in clinical to prevent acute GVHD, treat chronic GVHD, as well as enhance immune reconstitution and decrease leukemia relapse, all of which lead to improving transplant outcomes.
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- 2019
44. Immune Reconstitution after Allogeneic Hematopoietic stem Cell Transplantation in Children
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immune reconstitution (IR) ,CD4+ T-cell reconstitution (CD4+ IR) ,homeostatic peripheral expansion (HPE) ,allogeneic hematopoietic stem cell transplantation (HCT) ,thymopoiesis ,leukemia relapse ,viral reactivations (VR) ,graft-versus-host-disease (GvHD) - Abstract
An allogeneic hematopoietic stem cell transplantation is the only curative treatment option for children suffering from chemo-refractory leukemia or inborn errors such as metabolic diseases. During this therapy, the diseased bone marrow cells of the patient are replaced by stem cells from a healthy donor. After infusion of the donor stem cells, these cells find their way into the bone marrow of the patient, where they engraft and start differentiating into new immune cells. This essential process is called immune reconstitution. Since the first successful transplantation in 1968, the treatment of patients with this therapy has drastically improved over the last years. Despite of this, complications in this risky procedure are still common, causing 30-50% of patients to die after transplantation. This is why it is important to better understand what causes these complications, and how to better predict them. During my research, I found that children with a delayed immune reconstitution after their transplantation had much more complications and lower chance of survival. In particular a fast and adequate reconstitution of T-cells, the so-called soldiers of the immune system, is essential for lowering complications such as virus infections, graft-versus-host disease, and leukemia relapse. My research also describes different factors that affect the speed of T-cell reconstitution. These novel findings enable improvement of the treatment of patients who undergo a stem cell transplantation, which are expected to drastically enhance the survival chances of future transplantation recipients.
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- 2019
45. Immune Reconstitution after Allogeneic Hematopoietic stem Cell Transplantation in Children
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de Koning, C.C.H., Kuball, JHE, Boelens, Jaap-Jan, Nierkens, Stefan, and University Utrecht
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immune reconstitution (IR) ,CD4+ T-cell reconstitution (CD4+ IR) ,homeostatic peripheral expansion (HPE) ,allogeneic hematopoietic stem cell transplantation (HCT) ,thymopoiesis ,leukemia relapse ,viral reactivations (VR) ,graft-versus-host-disease (GvHD) - Abstract
An allogeneic hematopoietic stem cell transplantation is the only curative treatment option for children suffering from chemo-refractory leukemia or inborn errors such as metabolic diseases. During this therapy, the diseased bone marrow cells of the patient are replaced by stem cells from a healthy donor. After infusion of the donor stem cells, these cells find their way into the bone marrow of the patient, where they engraft and start differentiating into new immune cells. This essential process is called immune reconstitution. Since the first successful transplantation in 1968, the treatment of patients with this therapy has drastically improved over the last years. Despite of this, complications in this risky procedure are still common, causing 30-50% of patients to die after transplantation. This is why it is important to better understand what causes these complications, and how to better predict them. During my research, I found that children with a delayed immune reconstitution after their transplantation had much more complications and lower chance of survival. In particular a fast and adequate reconstitution of T-cells, the so-called soldiers of the immune system, is essential for lowering complications such as virus infections, graft-versus-host disease, and leukemia relapse. My research also describes different factors that affect the speed of T-cell reconstitution. These novel findings enable improvement of the treatment of patients who undergo a stem cell transplantation, which are expected to drastically enhance the survival chances of future transplantation recipients.
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- 2019
46. Two Occurrences of Leukemia Relapse Due to Mismatched HLA Loss After Haploidentical Stem Cell Transplantation From Different Family Donors With KIR Ligand Mismatch
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Atsushi Kikuta, Hitoshi Ohto, Kazuhiko Ikeda, Kazuhiro Mochizuki, Satoshi Ono, Hideki Sano, and Shogo Kobayashi
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Male ,endocrine system ,Transplantation Conditioning ,Adolescent ,KIR Ligand ,Graft vs Leukemia Effect ,Human leukocyte antigen ,03 medical and health sciences ,0302 clinical medicine ,Leukemia relapse ,Receptors, KIR ,immune system diseases ,HLA Antigens ,hemic and lymphatic diseases ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Homologous chromosome ,Medicine ,Humans ,Transplantation, Homologous ,Hla haplotypes ,business.industry ,Hematology ,Transplantation ,Killer Cells, Natural ,surgical procedures, operative ,Self Tolerance ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Histocompatibility ,Pediatrics, Perinatology and Child Health ,Immunology ,Female ,Stem cell ,Neoplasm Recurrence, Local ,business ,human activities ,030215 immunology ,Stem Cell Transplantation - Abstract
Mismatched HLA loss is a cause of leukemia relapse after HLA-haploidentical stem cell transplantation (haplo-SCT). We report a patient with a history of 2 occurrences of leukemia relapse due to mismatched HLA loss after haplo-SCT. He received haplo-SCT from his father but showed leukemia relapse with loss of the maternal HLA haplotype. He then underwent haplo-SCT from his mother, and developed relapse with loss of the paternal HLA haplotype. Both donors had killer cell immunoglobulin-like receptor-ligand mismatch but alloreactive natural killer cells could not prevent relapse. Second haplo-SCT should be conducted carefully for patients with relapse due to mismatched HLA loss.
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- 2019
47. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT
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Yener Koc, Zafar Gulbas, Didier Blaise, William Arcese, Dietrich W. Beelen, Simona Piemontese, Depei Wu, Arnon Nagler, Fabio Ciceri, Johanna Tischer, Benedetto Bruno, Annalisa Ruggeri, Ariane Boumendil, Giuseppe Irrera, Mohamad Mohty, Myriam Labopin, Mohamed Houhou, Christoph Schmid, Piemontese, Simona, Boumendil, Ariane, Labopin, Myriam, Schmid, Christoph, Ciceri, Fabio, Arcese, William, Koc, Yener, Gulbas, Zafar, Tischer, Johanna, Bruno, Benedetto, Wu, Depei, Blaise, Didier, Beelen, Dietrich, Irrera, Giuseppe, Ruggeri, Annalisa, Houhou, Mohamed, Mohty, Mohamad, and Nagler, Arnon
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Myeloid ,Medizin ,Leukemia relapse ,0302 clinical medicine ,Risk Factors ,hemic and lymphatic diseases ,Survival after relapse ,Cumulative incidence ,Societies, Medical ,Acute leukemia ,Hematology ,Myeloid leukemia ,lcsh:Diseases of the blood and blood-forming organs ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,Adolescent ,lcsh:RC254-282 ,03 medical and health sciences ,Young Adult ,Sex Factors ,Internal medicine ,medicine ,Humans ,ddc:610 ,Risk factor ,Molecular Biology ,Aged ,Retrospective Studies ,lcsh:RC633-647.5 ,business.industry ,Research ,Settore MED/15 ,Survival Analysis ,Transplantation ,030104 developmental biology ,Transplantation, Haploidentical ,Bone marrow ,Neoplasm Recurrence, Local ,business ,Stem Cell Transplantation - Abstract
Background As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Methods Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. Results The cumulative incidence of relapse at 3 years was 44% (35–53%) for ALL and 32% (27–36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). Conclusions Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%). Electronic supplementary material The online version of this article (10.1186/s13045-019-0751-4) contains supplementary material, which is available to authorized users.
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- 2019
48. Favourable outcome of de novo advanced phases of childhood chronic myeloid leukaemia
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Meinolf Suttorp, Natacha Maledon, Frédéric Millot, Joelle Guilhot, Adalet Meral Güneş, Krzysztof Kałwak, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri/Çocuk Sağlığı Ve Hastalıkları Bölümü., Güneş, Adalet Meral, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pediatric Hematology and Oncology (MHH), and Hannover Medical School [Hannover] (MHH)
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Time Factors ,Survival ,Databases, Factual ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Childhood leukemia ,Recommendations ,Leukemia relapse ,Treatment response ,Cancer staging ,Time factor ,European LeukemiaNet ,0302 clinical medicine ,Immunophenotyping ,Cancer Survivors ,hemic and lymphatic diseases ,Pathology ,Overall survival ,Molecular Targeted Therapy ,Registries ,Age of Onset ,Child ,Children ,Priority journal ,Chronic myeloid leukemia ,Stem cell transplantation ,Hematopoietic Stem Cell Transplantation ,Register ,Multicenter study ,3. Good health ,Chronic Myeloid Leukemia ,Imatinib ,Protein Tyrosine Kinase Inhibitor ,Clinical trial ,Haematopoiesis ,Retrospective study ,Treatment Outcome ,Oncology ,Molecularly targeted therapy ,030220 oncology & carcinogenesis ,Child, Preschool ,International registry ,Interphase-fish ,Cml patients ,Protein kinase inhibitor ,Cancer survivor ,Disease Progression ,Female ,Cancer chemotherapy ,Chronic myelogenous leukemia ,medicine.drug ,Human ,Adult ,Adverse event ,medicine.medical_specialty ,Adolescent ,Lymphoid blast crisis ,Major clinical study ,Blastic Phase ,Article ,03 medical and health sciences ,Internal medicine ,Advanced cancer ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,medicine ,Humans ,Factual database ,Prospective study ,Disease exacerbation ,Mortality ,neoplasms ,Survival rate ,Protein tyrosine kinase inhibitor ,Protein Kinase Inhibitors ,Chronic myeloid leukaemia ,Neoplasm Staging ,Tyrosine kinase inhibitors ,Chemotherapy ,business.industry ,Prognostic-factors ,Infant ,Follow up ,Transplantation ,030104 developmental biology ,Onset age ,Preschool child ,Comparative study ,business ,Controlled study - Abstract
Background Chronic myeloid leukaemia (CML) is very rare in children. The aim of the study is to report the experience within the I-CML-Ped study in children and adolescents presenting at diagnosis with advanced phase disease and to describe their characteristics and outcomes. Methods Of 479 children and adolescents enrolled in the international registry for childhood chronic myeloid leukaemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735 ), 36 children (7.5%) presented at initial diagnosis with CML in advanced phase according to the European LeukemiaNet criteria. Results Nineteen (4%) patients were diagnosed in accelerated phase (CML-AP), and among the 17 patients (3.5%) diagnosed in blastic phase (CML-BP), 70% presented with lymphoid immunophenotype. Initial treatment of CML-AP/CML-BP consisted of tyrosine kinase inhibitors (TKIs) with or without chemotherapy, leading to complete haematologic response in 33 of 36 (92%) patients. Seventeen patients proceeded to haematopoietic stem cell transplantation. At the last follow-up, 18 of 19 patients with de novo CML-AP are alive in at least major molecular response (MMR) (n = 16), in progression (n = 1) or in molecular relapse (n = 1) and 13 of 17 patients with de novo CML-BP are alive in at least MMR. Five-year overall survival rates are 94% (95% confidence interval [CI]: 66%–99%) and 74% (95% CI: 44%–89%) for patients diagnosed in CML-AP and CML-BP, respectively. Conclusion Children with advanced phase at diagnosis of CML seem to have a better survival rate than that reported for advanced phases evolving under TKI treatment.
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- 2018
49. Could Baking Soda Fight Leukemia Relapse After Stem Cell Transplant?
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Tracy Hampton
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Sodium bicarbonate ,business.industry ,medicine.medical_treatment ,General Medicine ,Hematopoietic stem cell transplantation ,medicine.disease ,chemistry.chemical_compound ,Leukemia ,Leukemia relapse ,chemistry ,Cancer research ,medicine ,Stem cell ,business - Published
- 2021
50. Post-transplant leukemia relapse in organs: biology. and behavior in 585 reports
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Isabel Cunningham
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Systemic therapy ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Leukemia relapse ,Bone Marrow ,Recurrence ,Internal medicine ,medicine ,Humans ,Dosing ,Biology ,Bone Marrow Transplantation ,PET-CT ,Leukemia ,business.industry ,Hematology ,Aplasia ,medicine.disease ,Post transplant ,030104 developmental biology ,030220 oncology & carcinogenesis ,business - Abstract
Resistance of extramedullary leukemia growth post-transplant prevents cure. Review of its behavior detailed in 585 published cases should lead to better treatment. Leukemic tumors were found up to 13 years after transplant, most in sites inaccessible to physical exam. In 83%, marrow was not in morphologic relapse; next relapse was most often extramedullary. Induction protocols alone produced few durable responses in acute leukemias and fatal marrow aplasia in 17 %. Overall, 120 patients survived over 2 years, 43 relapse-free up to 18 years, the majority after combined tumor-directed and systemic therapy. Overall median survival was 9 months. This review highlights how results can improve: by defining extent of leukemia involvement with scans before transplant, and emergently when leukemic tumor is found after, ablating tumor directly to abort metastasis, and determining dosing of systemic chemotherapy that protects, without ablating, donor marrow. Monitoring total body remission with body scans should increase transplant cures.
- Published
- 2021
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