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Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
Hu, B., Lin, X., Lee, H. C., Huang, X., Tidwell, R. S. S., Ahn, K. W., Hu, Z. H., Jabbour, E., Verstovsek, S., Ravandi, F., et al
Leukemia & lymphoma. 2020;:1-10
Abstract
While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9; p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1; p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9), p = .13] and AP [HR = 1.1 (0.6-2.1); p = .80] is less clear and should be determined on a case-by-case basis.
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Maintenance tyrosine kinase inhibitors following allo-HCT for chronic myeloid leukemia: A CIBMTR Study
DeFilipp, Z., Ancheta, R., Liu, Y., Hu, Z. H., Gale, R. P., Snyder, D., Schouten, H. C., Kalaycio, M., Hildebrandt, G. C., Ustun, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myeloid leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML transplanted from 2007-2014 who received maintenance TKI following HCT (n=89) as compared to no TKI maintenance (n=301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy prior to HCT. The majority of patients had disease beyond CP1 at HCT (n=240, 62%). The study was conducted as a landmark analysis, excluding patients that died, relapsed, had chronic graft-versus-host disease or were censored prior to Day 100 following HCT. Of the 89 patients receiving TKI maintenance, 77 (87%) received a single TKI while 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n=50), imatinib (n=27) and nilotinib (n=27). As measured from Day 100, the adjusted estimates for 5-year relapse (maintenance, 35% vs. no maintenance, 26%; p=0.11), leukemia-free survival (LFS, maintenance, 42% vs. no maintenance, 44%; p=0.65) or overall survival (OS, maintenance, 61% vs. no maintenance, 57%; p=0.61) did not significantly differ between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by the status of disease prior to transplant. In conclusion, our data did not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes in a Day 100 landmark analysis. The optimal approach to TKI administration in the post-transplant setting in CML remains undetermined.
PICO Summary
Population
Adult patients with CML transplanted from 2007-2014 (n=390)
Intervention
Maintenance TKI following HCT (n=89)
Comparison
no TKI maintenance (n=301)
Outcome
As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; ) or overall survival (maintenance, 61% versus no maintenance, 57%; ) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation.
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Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
Chhabra, S., Ahn, K. W., Hu, Z. H., Jain, S., Assal, A., Cerny, J., Copelan, E. A., Daly, A., DeFilipp, Z., Gadalla, S. M., et al
Blood advances. 2018;2(21):2922-2936
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Editor's Choice
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
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Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis
Chaudhury, S., Sparapani, R., Hu, Z. H., Nishihori, T., Abdel-Azim, H., Malone, A., Olsson, R., Hamadani, M., Daly, A., Bacher, U., et al
Biology of Blood & Marrow Transplantation. 2016;22(6):1056-64
Abstract
Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age < 18 years, n = 177) and young adults (age 18 to 29 years, n = 272) with the goal of identifying prognostic factors. Post-HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in <18-year and 74% and 60% in 18- to 29-year group, respectively, by univariate analysis (P = .1 and = .6). Five-year rates of OS for HLA matched sibling donor (MSD) and bone marrow (BM) stem cell source were 83% and 80%, respectively. In multivariate analysis there was no effect of age (<18 versus 18 to 29) or pre-HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P < .001) and recent HCT (2003 to 2010; P = .04). LFS was superior with MSD (P < .001), BM as graft source (P = .001), and performance scores > 90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD. Copyright © 2016 The American Society for Blood and Marrow Transplantation. All rights reserved.