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Impact of Donor Age on Allogeneic Hematopoietic Cell Transplantation Outcomes in Older Adults with Acute Myeloid Leukemia
Abid, M. B., Estrada-Merly, N., Zhang, M. J., Chen, K., Allan, D., Bredeson, C., Sabloff, M., Guru Murthy, G. S., Badar, T., Hashmi, S., et al
Transplantation and cellular therapy. 2023
Abstract
INTRODUCTION Allogeneic hematopoietic cell transplant (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit among matched unrelated donors (MUD), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) vs the best MUD? METHODS This retrospective cohort registry study accessed data from Center for International Blood and Marrow Transplant Research database (CIBMTR) in patients with AML 50 years or older undergoing alloHCT from older MSD (aged≥50) or younger MUD (aged≤35) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host-disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included non-relapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival (OS). RESULTS Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD whereas 2948 received transplant from a younger MUD. In multivariable analysis, compared to an alloHCT from older MSDs, younger MUDs conferred a decreased relapse risk (HR 0.86; p=.005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% vs 41%; p=.003), but was associated with an increased risk for chronic GVHD (HR 1.18; 95% CI, 1.08-1.29; p=.0002) and greater NRM only in the earlier period from 2011-2015 (HR 1.24; p=.016). The corresponding NRM rates were significantly lower in the more recent period from 2016-2018 (HR 0.78; p=.017). The adjusted 5-year DFS probability was 44% (95% CI, 42%-46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38%-43%) with an older MSD (p=.04). CONCLUSION In older patients with AML undergoing alloHCT, the use of younger MUDs is associated with a decreased relapse risk and improved DFS compared to older MSDs.
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Younger Matched Unrelated Donors Confer Decreased Relapse Compared to Older Sibling Donors in Older B-cell ALL Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
Abid, M. B., Merly, N. E., Zhang, M. J., Chen, K., Bredeson, C., Allan, D., Sabloff, M., Marks, D. I., Litzow, M., Hourigan, C., et al
Transplantation and cellular therapy. 2023
Abstract
INTRODUCTION While allogeneic hematopoietic cell transplant (alloHCT) offers cures for older patients with acute lymphoblastic leukemia (ALL), disease relapse remains a major issue. Whether matched sibling donors (MSD) are still the preferred donor choice compared to younger matched unrelated donors (MUD), in the contemporary era of improved transplant practices, remains unknown. METHODS This retrospective cohort registry study queried the Center for International Blood and Marrow Transplant Research database (CIBMTR) data in B-cell ALL patients 50 years or older, undergoing alloHCT from older MSDs (donor age ≥ 50) or younger MUDs (donor age ≤ 35) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft versus host disease (GVHD) prophylaxis strategies. The primary outcome was relapse risk whereas secondary outcomes included non-relapse mortality (NRM), GVHD, leukemia-free survival (LFS), and overall survival (OS). RESULTS Among 925 eligible patients in the study cohort, 386 underwent alloHCT with an older MSD (median donor age, 58) whereas 539 received transplant from a younger MUD (median donor age, 25). In multivariable analysis, younger MUDs conferred a significantly decreased risk of relapse (HR 0.68; p=.002) vs older MSDs. The adjusted cumulative incidence of relapse at 5 years was significantly lower with younger MUDs compared to older MSDs (26% vs 37%; p=.001). Younger MUDs were associated with a greater risk of chronic GVHD compared to older MSDs (HR 1.33; 95% CI, 1.10-1.61; p=.003). Compared to older MSDs, younger MUDs conferred an increased NRM (HR 1.38; p=.02) and higher adjusted cumulative incidence of NRM at 5 years (31% vs 22%; p=.006). There were no differences in OS or LFS rates of alloHCT with younger MUDs vs older MSDs (OS: HR 1.09; p=.37; DFS: HR 0.95; p=.57). CONCLUSION Younger MUDs could be considered as a possible way to prevent relapse after alloHCT in older adults with ALL. Combining the use of younger MUDs with improved strategies to reduce GVHD is worth further exploration to improve outcomes.
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Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors
Guru Murthy, G. S., Kim, S., Hu, Z. H., Estrada-Merly, N., Abid, M. B., Aljurf, M., Bacher, U., Badawy, S. M., Beitinjaneh, A., Bredeson, C., et al
JAMA oncology. 2022
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Abstract
IMPORTANCE Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.
PICO Summary
Population
People 50 years and older with myelodysplastic syndrome, identified from the CIBMTR database (n=1761)
Intervention
Matched sibling donor transplantation from an older donor 50 years and over (older MSD, n=646)
Comparison
Matched unrelated donor transplantation from a younger donor 35 years and under (younger MUD, n=1115)
Outcome
In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97;), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96;), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98).
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Network geometry of evidence from randomised controlled trials addressing donor selection and source of haematopoietic progenitor cells used in allogeneic transplantation: a systematic scoping review
Monaghan, M., Rizk, M., Pilon, S., Iyengar, A., Shorr, R., Tay, J., Maze, D., Bredeson, C., Hutton, B., Allan, D. S.
Transfusion medicine (Oxford, England). 2018
Abstract
BACKGROUND AND METHODS A scoping review of randomised controlled trials (RCTs) addressing source of cells and choice of donor for allogeneic haematopoietic cell transplantation (HCT) was performed to create a network of best evidence that allows us to identify new potential indirect comparisons for the strategic development of future studies that connect to the existing evidence network. RESULTS A total of 19 eligible RCTs (2589 total patients) were identified. Nine studies (1566 patients) compared clinical outcomes following the use of peripheral blood progenitor cells (PBPCs) with bone marrow (BM) from matched related donors (eight studies) or matched unrelated donors (one study). The remaining studies compared BM or PBPCs with various methods of BM stimulation or manipulation (six studies), compared different methods of surface molecule-based selection and/or depletion of grafts (two studies) or compared the optimal number of units for paediatric cord blood transplantation (two studies). No published RCTs compared different types of donors. The geometry of the evidence network was analysed to identify opportunities for potential novel indirect comparisons and to identify opportunities to expand the network. Few indirect comparisons are currently feasible due to small sample size and heterogeneity in patient diagnoses and demographics between treatment nodes in the network. CONCLUSION More RCTs that enrol greater numbers of similar patients are needed to leverage the current evidence network concerning donor choice and source of cells used in allogeneic HCT.
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Effect of donor age and donor relatedness on time to allogeneic hematopoietic cell transplantation in acute leukemia
Visram, A., Aziz, J., Bryant, A., Zhang, T., Cieniak, C., Hamelin, L., Landry, C., Morris, G., Mercer, D., Atkins, H., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Relapse following allogeneic hematopoietic cell transplantation (HCT) for acute leukemia can be reduced when pursued early after first complete remission. The impact of donor age and donor relatedness on the time from diagnosis to transplant in patients with acute leukemia was examined to clarify the design of future prospective studies that can address optimal donor choice. Files of 100 consecutive patients undergoing transplantation for leukemia were reviewed. Recipients of related (RD) and unrelated donors (UD) were not significantly different in terms of recipient gender, age, underlying diagnosis, disease risk index, graft source, or donor HLA match. UD were significantly younger than RD (median age 29 vs. 51, p<0.001). Multivariate linear regression revealed that when controlling for age of donor and recipient, the time from diagnosis to transplant was 35% longer with UD compared to a RD (p=0.018). No significant correlation was observed between donor or recipient age on length of time to transplant (p=0.134 and p=0.850, respectively), when controlling for other variables. The steps in UD procurement that contribute most to the longer time to transplant relate to activating the donor workup and scheduling the donor workup prior to cell collection. Understanding sources of delay in the transplant process will help transplant centers and UD registries reduce the time to transplant for patients with acute leukemia and will provide necessary insight for the design of prospective controlled studies that can address optimal donor choice.