-
1.
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.
-
2.
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.
-
3.
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
-
-
-
Free full text
-
-
Editor's Choice
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).
-
4.
Outcomes of Allogeneic Hematopoietic Cell Transplantation in T-cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research
Murthy, H. S., Ahn, K. W., Estrada-Merly, N., Alkhateeb, H. B., Bal, S., Kharfan-Dabaja, M. A., Dholaria, B., Foss, F., Gowda, L., Jagadeesh, D., et al
Transplantation and cellular therapy. 2022
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplant characteristics and outcomes after alloHCT are sparse. OBJECTIVE To describe outcomes of alloHCT in T-PLL and identify predictors of post-transplant relapse and survival. STUDY DESIGN We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research (CIBMTR) database on 266 patients with T-PLL who underwent alloHCT during 2008-2018. RESULTS The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% CI, 23.8-36.5%), 25.7% (95% CI, 20-32%), 41.9% (95% CI, 35.5-48.4%), and 32.4% (95% CI, 26.4-38.6%), respectively. In multivariable analyses, three variables were associated with inferior OS: myeloablative conditioning (MAC) (hazard ratio [HR] 2.18, p<0.0001); age older than 60 years (HR 1.61, p=0.0053); and suboptimal performance status defined by Karnofsky Performance Status (KPS) <90 (HR 1.53, p=0.0073). MAC also was associated with increased TRM (HR 3.31, p<0.0001), increased cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) (HR 2.94, p=0.0011) and an inferior disease-free survival (HR 1.86, p=0.0004). Conditioning intensity was not associated with relapse; however stable disease/progression correlated with increased risk of relapse (HR 2.13, p=0.0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Total Body Irradiation was not found to have any significant effect on OS, DFS or TRM. CONCLUSION Our data showed that reduced-intensity conditioning without in vivo T-cell depletion (that is, without ATG or alemtuzumab) prior to alloHCT was associated with long-term disease-free survival in patients with T-PLL who were 60 or younger or who had KPS >90 or had chemo-sensitive disease.
PICO Summary
Population
People with T-cell prolymphocytic leukaemia (T-PLL), identified from the CIBMTR database (n=266)
Intervention
Allogeneic haematopoietic stem cell transplantation
Comparison
None
Outcome
The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% CI, 23.8-36.5%), 25.7% (95% CI, 20-32%), 41.9% (95% CI, 35.5-48.4%), and 32.4% (95% CI, 26.4-38.6%), respectively. In multivariable analyses, three variables were associated with inferior OS: myeloablative conditioning (MAC) (hazard ratio [HR] 2.18); age older than 60 years (HR 1.61); and suboptimal performance status defined by Karnofsky Performance Status (KPS) <90 (HR 1.53). MAC also was associated with increased TRM (HR 3.31), increased cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) (HR 2.94) and an inferior disease-free survival (HR 1.86). Conditioning intensity was not associated with relapse; however stable disease/progression correlated with increased risk of relapse (HR 2.13). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Total Body Irradiation was not found to have any significant effect on OS, DFS or TRM.
-
5.
The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis
Mei, M., Pillai, R., Kim, S., Estrada-Merly, N., Afkhami, M., Yang, L., Meng, Z., Abid, M. B., Aljurf, M., Bacher, U., et al
Haematologica. 2022
Abstract
Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (alloHCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range: 28-77) who underwent alloHCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, p=0.049) or high (HR=3.22, p=0.0004) correlated significantly with overall survival (OS). When the molecularly informed CPSS-Mol was applied, a high CPSS-Mol score (HR=2 p=0.0079) correlated significantly with OS. The most common somatic mutations were ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased OS (HR=1.70 [95%CI: 1.11-2.60], p=0.0147 and HR=2.72 [95%CI: 1.37-5.39], p=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (DFS) (HR=1.66 [95%CI: 1.11-2.49], p=0.0138, HR=1.79 [95%CI: 1.06- 3.03], p=0.0293, and HR=2.94 [95%CI: 1.50-5.79], p=0.0018 respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, p=0.0201). Nonetheless, the impact specifically of TP53 mutations should be interpreted cautiously given its rarity in CMML. We calculated the goodness of fit measured by Harrell's C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have provided the mutational landscape in patients with CMML who underwent alloHCT, and we demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond the CPSS.
-
6.
Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improves Transplant Outcomes in Older MDS Patients
Oran, B., Ahn, K. W., Fretham, C., Beitinjaneh, A., Bashey, A., Pawarode, A., Wirk, B., Scott, B. L., Savani, B. N., Bredeson, C., et al
Transplantation and cellular therapy. 2021
-
-
-
Free full text
-
Editor's Choice
Abstract
Reduced-intensity conditioning (RIC) regimens developed to extend allogeneic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the two most commonly used RIC regimens, intravenous use of fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in myelodysplastic syndrome (MDS). Through CIBMTR, we identified 1045 MDS patients aged = 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using RIC. CIBMTR's definition of RIC was used: a regimen that incorporated an intravenous busulfan total dose = 7.2 mg/kg, or a low-dose melphalan total dose of = 150 mg/m(2). The two groups, FluBu (n=697) and FluMel (n=448), were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44% (p=0.0001). Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%, p=0.0001). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, p=0.02, and 35% vs. 27% at 3 years, p=0.01). Overall survival (OS) was comparable at 1 year (63% vs. 61%, p=0.4) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%, p=0.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
PICO Summary
Population
Patients with myelodysplastic syndrome aged >/=60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor, and were reported to the CIBMTR registry (n=1045)
Intervention
Reduced intensity regimen incorporating an intravenous busulfan total dose = 7.2 mg/kg (FluBu, n=697)
Comparison
Reduced intensity regimen incorporating a low-dose melphalan total dose of = 150 mg/m(2) (FluMel, n=448)
Outcome
The two groups were comparable for disease and transplant-related characteristics except for the more frequent use of anti-thymocyte globulin or alemtuzumab in the FluBu group (39% vs. 31%). The median age was 67 in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% vs. 44%. Transplant-related mortality (TRM) was higher with FluMel compared with FluBu (26% vs. 16%). Since the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 40% at 1 year, and 35% vs. 27% at 3 years). Overall survival (OS) was comparable at 1 year (63% vs. 61%) but significantly improved with FluMel compared with FluBu at 3 years (46% vs. 39%). Our results suggest that FluMel is associated with superior DFS compared with FluBu due to reduced RI in older MDS patients.
-
7.
Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myeloid Leukemia and Myelodysplastic Syndromes with Low/Intermediate, but not High Disease Risk Index: A CIBMTR Study: Superior DFS with MAC compared to RIC HCT in AML/MDS with low/intermediate risk DRI
Bejanyan, N., Zhang, M., Bo-Subait, K., Brunstein, C., Wang, H., Warlick, E. D., Giralt, S., Nishihori, T., Martino, R., Passweg, J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
-
-
-
Free full text
-
Editor's Choice
Abstract
Myeloablative (MAC) as compared to reduced-intensity conditioning (RIC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, disease specific risk factors in AML/MDS can further inform when MAC vs. RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the disease risk index (DRI) in 4387 adults (age 40-65 years) to identify the impact of conditioning intensity. In the low/intermediate risk DRI cohort, RIC was associated with lower non-relapse mortality (NRM) (HR=0.74, 95% CI 0.62-0.88; p<0.001), but significantly higher relapse risk (HR=1.54, 95% CI 1.35-1.76; p<0.001) and thus inferior disease-free survival (DFS) (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/very high risk DRI cohort, RIC resulted in marginally lower NRM (HR=0.83, 95% CI 0.68-1.00; p=0.051), and significantly higher relapse risk (HR=1.23, 95% CI 1.08-1.41; p=0.002) leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for AML/MDS with low/intermediate risk DRI, but similar benefit to RIC in high/very high risk DRI. Novel MAC regimens with less toxicity could benefit all, but more potent anti-neoplastic approaches are needed for the high/very high risk DRI group.
PICO Summary
Population
Adult patients aged 40-65 years with acute myeloid leukaemia or myelodysplastic syndrome (AML/MDS) (n=4387)
Intervention
Reduced intensity conditioning (RIC) and low/intermediate risk (n=999), RIC and high/very high risk (n=728)
Comparison
Myeloablative conditioning (MAC) and low/intermediate risk (n=1539), MAC and high/very high risk (n=1121)
Outcome
In the low/intermediate risk disease risk index (DRI) cohort, RIC was associated with lower non-relapse mortality (NRM) , but significantly higher relapse risk and thus inferior disease-free survival (DFS). In the high/very high risk DRI cohort, RIC resulted in marginally lower NRM, and significantly higher relapse risk leading to similar DFS using either RIC or MAC.
-
8.
Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant
Ghosh, N., Ahmed, S., Ahn, K. W., Khanal, M., Litovich, C., Aljurf, M., Bacher, V. U., Bredeson, C., Epperla, N., Farhadfar, N., et al
JAMA oncology. 2020
-
-
Free full text
-
Abstract
Importance: Reduced-intensity conditioning and nonmyeloablative conditioning (RIC-NMAC) regimens are frequently used in allogeneic hematopoietic cell transplant (HCT) for non-Hodgkin lymphoma. However, the optimal RIC-NMAC regimen in allogeneic HCT for non-Hodgkin lymphoma is not known. Objective: To investigate whether RIC-NMAC regimens at a higher end of the intensity spectrum are associated with increased nonrelapse mortality and lower overall survival compared with RIC-NMAC regimens at the lower end of the intensity spectrum in patients with non-Hodgkin lymphoma undergoing allogeneic HCT. Design, Setting, and Participants: This cohort study used data from 1823 adult patients with non-Hodgkin lymphoma in the Center for International Blood and Marrow Transplant Research registry. Included patients underwent allogeneic HCT using matched related or unrelated donors between January 2008 and December 2016. Statistical analysis was performed from June 1, 2019, to February 10, 2020. Interventions: Patients received 1 of 4 RIC-NMAC regimens: fludarabine-intravenous busulfan (Flu-Bu), approximately 6.4 mg/kg (n = 458); fludarabine-melphalan (Flu-Mel140), 140 mg/m2 (n = 885); fludarabine-cyclophosphamide (Flu-Cy) (n = 391); or Flu-Cy with 2 Gy total body irradiation (Flu-Cy-2GyTBI) (n = 89). Main Outcomes and Measures: The primary outcome was overall survival. Secondary outcomes were nonrelapse mortality, incidence of relapse, progression-free survival, and the incidence of acute and chronic graft-vs-host disease (GVHD). Results: Of 1823 patients, 1186 (65%) were male, with a mean (SD) age of 54.8 (9.9) years. The 4-year adjusted OS was 58% in the Flu-Bu cohort, 67% in the Flu-Cy-2GyTBI cohort, 49% in the Flu-Mel140 cohort, and 63% in the Flu-Cy cohort (P < .001). After adjustment for age, Karnofsky performance score, HCT comorbidity index, NHL subtype, remission status at HCT, and the use of antithymocyte globulin or alemtuzumab, the regression analysis showed a significantly higher mortality risk associated with Flu-Mel140 compared with Flu-Bu (hazard ratio [HR], 1.34; 95% CI, 1.13-1.59; P < .001). Compared with the Flu-Cy cohort, the Flu-Mel140 cohort had a higher risk of chronic GVHD (HR, 1.38; 95% CI, 1.15-1.65; P < .001). The Flu-Mel140 regimen was associated with a higher nonrelapse mortality risk (HR, 1.78; 95% CI, 1.37-2.31; P < .001) compared with the Flu-Bu regimen. Conclusions and Relevance: The findings suggest that use of the more intense RIC-NMAC regimen, Flu-Mel140, may have a negative association with overall survival and may be associated with higher nonrelapse mortality. The Flu-Bu and Flu-Cy regimens with or without 2GyTBI regimens appeared to provide comparable overall survival.
-
9.
Weighty choices: selecting optimal G-CSF doses for stem cell mobilization to optimize yield
Farhadfar, N., Hsu, J. W., Logan, B. R., Sees, J. A., Chitphakdithai, P., Sugrue, M. W., Abdel-Azim, H., Anderlini, P. N., Bredeson, C., Chhabra, S., et al
Blood advances. 2020;4(4):706-716
-
-
Free full text
-
Abstract
There are limited data on the effect of donor body mass index (BMI) on peripheral blood stem cell (PBSC) mobilization response to granulocyte colony-stimulating factor (G-CSF), especially in unrelated donors. Obesity has been associated with persistent leukocytosis, elevated circulating progenitor cells, and enhanced stem cell mobilization. Therefore, we hypothesized that adequate collection of CD34+ cells may be achieved with lower doses (per kilogram of body weight) of G-CSF in donors with higher BMI compared with donors with lower BMI. Using the Center for International Blood and Marrow Transplant Research database, we evaluated the impact of donor BMI on G-CSF-mobilized PBSC yield in healthy unrelated donors. We examined 20 884 PBSC donations collected at National Marrow Donor Program centers between 2006 and 2016. We found significantly higher collection yields in obese and severely obese donors compared with normal and overweight donors. An increase in average daily G-CSF dose was associated with an increase in stem cell yield in donors with normal or overweight BMI. In contrast, an increase in average daily G-CSF dose beyond 780 mug per day in obese and 900 mug per day in severely obese donors did not increase cell yield. Pain and toxicities were assessed at baseline, during G-CSF administration, and postcollection. Obesity was associated with higher levels of self-reported donation-related pain and toxicities in the pericollection and early postdonation recovery periods. This study suggests a maximum effective G-CSF dose for PBSC mobilization in obese and severely obese donors, beyond which higher doses of G-CSF add no increased yield.
-
10.
Pre-transplant marital status and hematopoietic cell transplantation outcomes
Tay, J., Beattie, S., Bredeson, C., Brazauskas, R., He, N., Ahmed, I. A., Aljurf, M., Askar, M., Atsuta, Y., Badawy, S., et al
Current oncology (Toronto, Ont.). 2020;27(6):e596-e606
Abstract
BACKGROUND Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. METHODS We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. RESULTS We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). CONCLUSIONS Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.