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Allogeneic hematopoietic cell transplantation for patients with TP53 mutant or deleted chronic lymphocytic leukemia: Results of a prospective observational study
Schetelig, J., Hoek, J., Stilgenbauer, S., Middeke, J. M., Andersen, N. S., Fox, C. P., Lenhoff, S., Volin, L., Shimoni, A., Schroyens, W., et al
Bone marrow transplantation. 2020
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Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation
van Gelder, M., de Wreede, L. C., Bornhauser, M., Niederwieser, D., Karas, M., Anderson, N. S., Gramatzki, M., Dreger, P., Michallet, M., Petersen, E., et al
Bone Marrow Transplantation. 2017;52(3):372-380
Abstract
Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
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3.
Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)
Schetelig, J., de Wreede, L. C., Andersen, N. S., Moreno, C., van Gelder, M., Vitek, A., Karas, M., Michallet, M., Machaczka, M., Gramatzki, M., et al
British Journal of Haematology. 2017;178(4):521-533
Abstract
The best approach for allogeneic haematopoietic stem cell transplantations (alloHCT) in patients with chronic lymphocytic leukaemia (CLL) is unknown. We therefore analysed the impact of procedure- and centre-related factors on 5-year event-free survival (EFS) in a large retrospective study. Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analysed by multivariable Cox proportional hazards models with a frailty component to investigate unexplained centre heterogeneity. Five-year EFS of the whole cohort was 37% (95% confidence interval [CI], 34-42%). Larger numbers of CLL alloHCTs (hazard ratio [HR] 0.96, P = 0.002), certification of quality management (HR 0.7, P = 0.045) and a higher gross national income per capita (HR 0.4, P = 0.04) improved EFS. In vivo T-cell depletion (TCD) with alemtuzumab compared to no TCD (HR 1.5, P = 0.03), and a female donor compared to a male donor for a male patient (HR 1.4, P = 0.02) had a negative impact on EFS, but not non-myeloablative versus more intensive conditioning. After correcting for patient-, procedure- and centre-characteristics, significant variation in centre outcomes persisted. In conclusion, further research on the impact of centre and procedural characteristics is warranted. Non-myeloablative conditioning appears to be the preferable approach for patients with CLL.
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4.
Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation
Schetelig, J., de Wreede, L. C., van Gelder, M., Andersen, N. S., Moreno, C., Vitek, A., Karas, M., Michallet, M., Machaczka, M., Gramatzki, M., et al
Bone Marrow Transplantation. 2017;52(4):552-560
Abstract
For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%. Higher age, lower performance status, unrelated donor type and unfavorable sex-mismatch had a significant adverse impact on 2-year NRM. Two-year NRM was calculated for good- and poor-risk reference patients. Predicted 2-year-NRM was 11 and 12% for male and female good-risk patients compared with 42 and 33% for male and female poor-risk patients. For 5-year EFS, age, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited prognosis either on or after failure of targeted therapy should still be considered for alloHCT.
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5.
Outcome of patients with chronic myeloid leukemia and a low-risk score: allogeneic hematopoietic stem cell transplantation in the era of targeted therapy. A report from the EBMT Chronic Malignancies Working Party
Koenecke, C., Heim, D., van Biezen, A., Heuser, M., Aljurf, M., Kyrcz-Krzemien, S., Volin, L., de Souza, C. A., Gedde-Dahl, T., Sengeloev, H., et al
Bone Marrow Transplantation. 2016;51(9):1259-61