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1.
Incidence and Risk Factors of Early Onset VOD/SOS Differ in Younger vs Older Adults After Stem Cell Transplantation
Marcoux, C., Saliba, R. M., Wallis, W., Khazal, S. J., Ragoonanan, D., Rondon, G., Tewari, P., Popat, U. R., Oran, B., Olson, A. L., et al
Blood advances. 2024
Abstract
Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-SCT). While increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with post-transplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single center analysis of adult patients 18 years or older undergoing allo-SCT (N=1561) using predominately PTCy as GVHD prophylaxis (72%). We found a higher rate of VOD at 16.8% (20/119) in those aged ≤ 25 years compared to 3.8% (55/1442) in those >25 years, with unique predictors of VOD within each cohort. Multivariate classification and regression tree (CART) analysis confirmed age as the primary independent determinant of the rate of VOD. Within patients aged 18-25 years, disease risk index (DRI) (31% with high/very high DRI vs 12% low/intermediate DRI; p=0.03) and prior lines of chemotherapy (24% with >1 vs 6% with ≤1, p=0.03) were the strongest predictors of VOD. Incidence of VOD in patients > 25 years of age consistently ranged between 3-5% across most risk factors evaluated, with only hepatic factors (baseline elevation of bilirubin, aspartate transferase (AST), alanine aminotransferase (ALT)) or gemtuzumab exposure associated with increased rates of VOD. There was no significant difference in rates of VOD in those receiving PTCy compared to those receiving alternate GVHD prophylaxis. Our data highlight the differences in incidence and predictors in VOD between younger (≤25) and older (>25) adults undergoing allo-SCT.
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Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience
Pasvolsky, O., Ghanem, S., Milton, D. R., Rauf, M., Tanner, M. R., Bashir, Q., Srour, S., Saini, N., Lin, P., Ramdial, J., et al
Blood cancer journal. 2024;14(1):4
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Editor's Choice
Abstract
The prognostic impact of additional copies of chromosome 1q (1q + ) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008-2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative ≥VGPR before autoSCT (HR 0.52, p = 0.013) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03, p = 0.003). On multivariate analysis for OS, achieving MRD negative ≥VGPR at best post-transplant response was associated with superior survival (0.29, p < 0.001), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, p = 0.030, 2.33, p = 0.023 and 3.00, p = 0.047, respectively). In conclusion, patients with 1q+ NDMM, especially 1q amplification, have inferior survival outcomes compared to standard-risk disease after upfront autoSCT, though outcomes are better than other high-risk cytogenetic abnormalities.
PICO Summary
Population
Adults with newly-diagnosed myeloma (NDMM) patients with 1q21 gain/amplification (3 or >/=4 copies of 1q, respectively) that received autoSCT between from a single centre in USA (n=213)
Intervention
Assess the prognostic impact of additional copies of chromosome 1q (1q+) on autologous transplantation outcomes
Comparison
None
Outcome
At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved very good partial response or better (>/=VGPR) and 38% and 50% achieved MRD-negative >/=VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative >/=VGPR before autoSCT (HR 0.52) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03). On multivariate analysis for OS, achieving MRD negative >/=VGPR at best post-transplant response was associated with superior survival (0.29), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, 2.33, and 3.00, respectively).
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3.
Molecular disparity of HLA-DPB1 is associated with the development of subsequent solid cancer after allogeneic hematopoietic stem cell transplantation
Zou, J., Kongtim, P., Oran, B., Srour, S. A., Greenbaum, U., Carmazzi, Y., Rondon, G., Ciurea, S. O., Ma, Q., Shpall, E. J., et al
Cancer. 2023
Abstract
BACKGROUND An increased incidence of subsequent solid cancers (SSCs) has been reported in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT), and SSC is associated with inferior mortality and morbidity. Previous studies showed that the incidence of SSC is significantly higher in those who underwent allo-HSCT from HLA-mismatched donors, suggesting that persistent alloimmunity may predispose patients to SSCs. It was recently reported that, in a cohort of patients who received allo-HSCT from an unrelated donor matched at HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 loci, HLA-DPB1 alloimmunity determined by high mismatched eplets (MEs) and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score (PS), was associated with relapse protection and increased risk of acute graft-versus-host disease (GVHD). METHODS In the present study, the impact of HLA-DPB1 alloimmunity assessed by molecular mismatch algorithms on the development of SSCs in a cohort of 1514 patients who underwent allo-HSCT for hematologic malignancies was further investigated. ME load at the HLA-DPB1 locus was measured using the HLAMatchmaker module incorporated in HLA Fusion software, and the PS for mismatched HLA-DPB1 was calculated using the HSCT module from the PIRCHE online matching service. RESULTS In multivariable analysis after adjusting for baseline risk factors, higher ME, PS-I, and PS-II in the GVH direction, but not in the HVG direction, were associated with an increased risk of SSCs (ME: subdistribution hazard ratio [SHR] 1.58, p = .01; PS-I: SHR 1.59, p = .009; PS-II: SHR 1.71, p = .003). In contrast, nonpermissive HLA-DPB1 mismatches defined by the conventional T-cell epitope algorithm were not predictive of the risk of SSCs. Moreover, posttransplant cyclophosphamide-based GVHD prophylaxis was associated with a reduced risk of SSC (SHR 0.34, p = .021). CONCLUSIONS These results indicate for the first time that increased GVH alloreactivity could contribute to the development of SSCs in allo-HSCT survivors.
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Haploidentical vs matched unrelated donors for patients with ALL: donor age matters more than donor type
Mehta, R. S., Marin, D. C., Alousi, A., Kanakry, C. G., Champlin, R. E., Rezvani, K., Shpall, E. J., Page, K. M., Gadalla, S. M., Weisdorf, D. J., et al
Blood advances. 2023
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Editor's Choice
Abstract
Haploidentical hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis yields similar overall survival (OS) as HLA-matched-unrelated donor (MUD) HCT with conventional prophylaxis. Given prognostic implications of donor age, we investigated the impact of donor age ["younger" (<35 years; n=868) vs "older" (>35 years; n=418)] and donor-type [haploidentical (n=373) vs MUD (n=913)] on OS in adult patients with acute lymphoblastic leukemia (ALL). Older donor age was independently associated with significantly poor OS [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.10-1.71, p=0.005]; donor-type was not. Next, we directly compared the outcomes of a younger haploidentical donor (n=187) vs an older MUD (n=232). In this cohort, more patients in the haploidentical group had B-cell immunophenotype (89% vs 77%, respectively, p<0.001), poor cytogenetics (61% vs 51%, respectively, p=0.44), Philadelphia chromosome-negative (53% vs 48%, respectively, p=0.38), received bone marrow graft (42% vs 16%, respectively, p<0.001) and reduced-intensity conditioning (45% vs 23%, respectively, p<0.001). In multivariate analysis, the older MUD group was associated with a significantly higher risk of chronic GVHD [HR 1.91, 95% CI 1.28-2.85, p=0.002], higher non-relapse mortality (HR 2.75, 95% CI 1.51-4.99, p=0.001), lower relapse (HR 0.50, 95% CI 0.31-0.82, p=0.006) and poorer OS (HR 1.77, 95% CI 1.16-2.71, p=0.008). Despite a higher risk of relapse, younger donor haploidentical HCT with PTCy prophylaxis may be preferred over an older MUD HCT with conventional prophylaxis in patients with ALL due to lower nonrelapse mortality and better OS. Further analysis comparing the effect of donor age in haploidentical-PTCy vs MUD-PTCy is warranted.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia undergoing matched unrelated donor or haploidentical transplantation and reported to the CIBMTR registry (n=1286)
Intervention
Donor age under 35 years (younger, n=868); Then younger haploidentical donor (n=187)
Comparison
Older donor age over 35 years (n=418); Then older matched unrelated donor (older MUD, n=232)
Outcome
Older donor age was independently associated with significantly poor OS [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.10-1.71,]; donor-type was not. Next, we directly compared the outcomes of a younger haploidentical donor (n=187) vs an older MUD (n=232). In this cohort, more patients in the haploidentical group had B-cell immunophenotype (89% vs 77%, respectively), poor cytogenetics (61% vs 51%, respectively), Philadelphia chromosome-negative (53% vs 48%, respectively), received bone marrow graft (42% vs 16%, respectively) and reduced-intensity conditioning (45% vs 23%, respectively). In multivariate analysis, the older MUD group was associated with a significantly higher risk of chronic GVHD [HR 1.91, 95% CI 1.28-2.85], higher non-relapse mortality (HR 2.75, 95% CI 1.51-4.99), lower relapse (HR 0.50, 95% CI 0.31-0.82) and poorer OS (HR 1.77, 95% CI 1.16-2.71).
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5.
Impact of Donor Age in Haploidentical-Post-Transplantation Cyclophosphamide versus Matched Unrelated Donor Post-Transplantation Cyclophosphamide Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia
Mehta, R. S., Ramdial, J., Marin, D., Alousi, A., Kanakry, C. G., Champlin, R. E., Rezvani, K., Shpall, E. J., Page, K., Gadalla, S. M., et al
Transplantation and cellular therapy. 2023;29(6):377.e1-377.e7
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Editor's Choice
Abstract
Haploidentical hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis is associated with inferior overall survival (OS) compared to HLA-matched unrelated donor (MUD) HCT with PTCy prophylaxis in patients receiving reduced-intensity conditioning (RIC). Given prognostic implications of donor age, we investigated the differences in outcomes of patients with acute myeloid leukemia (AML; n = 775) undergoing RIC-HCT with a younger MUD (age <35 years; n = 84) versus a younger haploidentical donor (age <35 years; n = 302) versus an older haploidentical donor (age ≥35 years; n = 389). The older MUD group was excluded from the analysis because of small numbers. The younger haploidentical donor group (median age, 59.5 years) was somewhat younger than the younger MUD group (median age, 66.8 years) and the older haploidentical donor group (median age, 64.7 years). More patients in the MUD group received peripheral blood grafts (82%) compared to the haploidentical donor groups (55% to 56%). In multivariate analysis, compared to the younger MUD group, the younger haploidentical donor group (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.22 to 3.12; P = .005) and the older haploidentical donor group (HR, 2.36; 95% CI, 1.50 to 3.71; P < .001) had a significantly inferior OS, and the younger haploidentical donor group (HR, 3.72; 95% CI, 1.39 to 9.93; P = .009) and older haploidentical donor group (HR, 6.91; 95% CI, 2.75 to 17.39; P < .001) had a significantly higher risk of nonrelapse mortality. The older haploidentical group had a significantly higher risk of grade II-IV acute GVHD (HR, 2.29; 95% CI, 1.38 to 3.80; P = .001) and grade III-IV acute GVHD (HR, 2.70; 95% CI, 1.09 to 6.71; P = .03). There were no significant differences across the groups in the incidence of chronic GVHD or relapse. Among adult AML patients in CR undergoing RIC-HCT with PTCy prophylaxis, a young MUD may be preferred over a young haploidentical donor.
PICO Summary
Population
Adults with acute myeloid leukemia undergoing reduced intensity conditioning and transplant, identified from the CIBMTR database (n = 775)
Intervention
Younger (age <35 years) matched unrelated donor (MUD, n = 84)
Comparison
Younger (age <35 years) haploidentical donor (n = 302) older (age ≥35 years) haploidentical donor (n = 389)
Outcome
The younger haploidentical donor group (median age, 59.5 years) was somewhat younger than the younger MUD group (median age, 66.8 years) and the older haploidentical donor group (median age, 64.7 years). More patients in the MUD group received peripheral blood grafts (82%) compared to the haploidentical donor groups (55% to 56%). In multivariate analysis, compared to the younger MUD group, the younger haploidentical donor group (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.22 to 3.12) and the older haploidentical donor group (HR, 2.36; 95% CI, 1.50 to 3.71) had a significantly inferior OS, and the younger haploidentical donor group (HR, 3.72; 95% CI, 1.39 to 9.93) and older haploidentical donor group (HR, 6.91; 95% CI, 2.75 to 17.39) had a significantly higher risk of nonrelapse mortality. The older haploidentical group had a significantly higher risk of grade II-IV acute GVHD (HR, 2.29; 95% CI, 1.38 to 3.80) and grade III-IV acute GVHD (HR, 2.70; 95% CI, 1.09 to 6.71). There were no significant differences across the groups in the incidence of chronic GVHD or relapse.
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6.
Effect of donor age in patients with acute myeloid leukemia undergoing haploidentical hematopoietic cell transplantation vary by conditioning intensity and recipient age
Saliba, R. M., Kanakry, C. G., Gadalla, S., Kebriaei, P., Rezvani, K., Champlin, R. E., Shpall, E. J., Weisdorf, D., Mehta, R. S.
American journal of hematology. 2023
Abstract
We investigated the impact of donor age (younger [≤35 years] vs. older [>35 years]) after accounting for other non-HLA and HLA factors on outcomes of patients with acute myeloid leukemia undergoing HLA-haploidentical hematopoietic cell transplantation (n = 790). The effect differed by conditioning-partly related to the differences in the recipient age in myeloablative (MAC; median 46 years) versus reduced-intensity/non-myeloablative conditioning (RIC/NMA; median 61 years) groups. With MAC (n = 320), donor age had no impact on acute graft-versus-host disease (GVHD), but older donors were associated with a significantly higher risk of chronic GVHD (hazard ratio [HR]: 1.6, 95% confidence interval [CI]: 1.10-2.30, p = .02) independent of recipient age and other factors. Donor age had no impact on either relapse or non-relapse mortality (NRM). The impact of donor/recipient age on overall survival changed over time. Older donors were associated with significantly higher late overall mortality (>6 months) in younger recipients (≤ 50 years; HR: 2.2, 95% CI: 1.03-4.6, p = .04) but not older recipients. With RIC/NMA (n = 470), neither recipient's nor donor's age influenced the risk of GVHD. Donor age had no significant impact on the risk of relapse, but older donors were associated with a significantly higher risk of NRM (HR: 1.6, 95% CI: 1.02-2.6, p = .04) independent of recipient age. Older donor age was associated with significantly higher late overall mortality (>9 months) in older recipients (>50 years; HR: 1.66, 95% CI: 1.0-2.67; p = .049) but not in younger recipients. Donor selection based on donor age may require a tailored approach for a particular recipient.
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7.
Characteristics and outcomes of patients with multiple myeloma who developed therapy-related acute myeloid leukemia and myelodysplastic syndrome following autologous cell transplantation
Yalniz, F. F., Greenbaum, U., Pasvolsky, O., Milton, D. R., Kanagal-Shamanna, R., Ramdial, J., Srour, S., Mehta, R., Alousi, A., Popat, U. R., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing the therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). METHODS We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1/1/2000 and 12/31/2018, and later developed t-MDS/AML. RESULTS Among the 2982 patients that underwent at least one Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n=52; AML, n=3). The median age at t-MDS/AML diagnosis was 66 years (range, 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis was 58.5 months (range, 6-206 months). At diagnosis, all 3 patients with tAML and 65% of those with tMDS had high-risk disease, per ELN2022 and R-IPSS, respectively, and 62% had TP53 gene mutations. Patients who developed t-MDS/AML were older at MM diagnosis (median: 61 vs. 59 years; p=0.06), more often were male (73% vs. 58%; p=0.029), received more than 2 years of lenalidomide maintenance (57% vs. 39%; p=0.014) and experienced complete remission more frequently following Auto-HCT compared to those who did not develop t-MDS/AML (56% vs. 40%; p=0.012). In a multivariable model, male gender, advanced age at MM diagnosis, experiencing complete remission after Auto-HCT, and lenalidomide maintenance were independent predictors of developing t-MDS/AML. Among the patients who developed t-MDS/AML, 14 (25%) underwent allogeneic hematopoietic stem transplant (Allo-HCT). After a median follow-up of 9.9 months from t-MDS/AML diagnosis, the median overall survival (OS) after t-MDS/AML diagnosis was 11.8 months for all patients, and 18.2 months vs. 11.1 months for Allo-HCT recipients vs. nonrecipients, respectively (P=0.25). On univariate analysis, receiving an alkylator as induction for MM (hazard ratio [95% CI]: 2.9 [1.3-6.3]; P=0.009), age > 60 years (3.1 [1.2-8.2]; P=0.025), and higher risk R-IPSS (2.7 [1.3-6.0]; P=0.011) predicted worse OS after t-MDS/AML diagnosis. None of these retained significance in the multivariable analysis. CONCLUSION T-MDS/AML following an Auto-HCT for MM is associated with aggressive disease characteristics, including high risk cytogenetics and TP53 mutations. The outcomes of patients remain poor, even with Allo-HCT. A better understanding of disease biology and novel therapeutic approaches is warranted.
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8.
Myeloablative Fractionated Busulfan for Allogeneic Stem Cell Transplant in Older Patients or Patients with Comorbidities
Popat, U. R., Pasvolsky, O., Bassett, R., Mehta, R. S., Olson, A. L., Chen, J., Alousi, A. M., Al-Atrash, G., Bashir, Q., Gulbis, A. M., et al
Blood advances. 2023
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Editor's Choice
Abstract
Traditional conditioning regimens for patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce non-relapse mortality (NRM), while retaining anti-leukemic effects. Here, we performed a phase II trial for adults with hematological malignancies receiving matched related or unrelated alloHCT. Participants received busulfan 80mg/m2 outpatient on days -20 and -13 before transplant. Fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve a target area under the curve of 20,000mol/min for the whole course. The primary endpoint was day 100 NRM. Seventy-eight patients were included, with a median age of 61 (range 39-70) years, transplanted for acute leukemia (24%), MDS (27%), or MPD/CML (44%). HCT specific comorbidity index (HCT-CI) was >3 in 34 (44%). With a median follow-up of 36.4 (range 2.9-51.5) months, 100-day, 1-year and 3-year NRM was 3.8% (95%CI, 0-8.1%), 8% (95%CI, 2-14%), and 9.3% (95%CI, 2.6-15.9%), without a significant difference by age or HCT-CI score. One-year and 3-year relapse incidence was 10% (95%CI, 4-17%) and 18% (95%CI, 9-27%), respectively. Three-year overall survival was 80% (95%CI, 72-90%) and was similar for patients >60 and <60 years of age, as well as those with HCT-CI>3 and HCT-CI<3. Overall, we found that a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities.
PICO Summary
Population
Adults with haematological malignancies receiving matched related or unrelated allogeneic transplant, from a single centre in USA (n=78).
Intervention
Busulfan 80mg/m2 outpatient on days -20 and -13 before transplant, fludarabine 40mg/m2 on days -6 to -2 followed by busulfan dosed to achieve a target area under the curve of 20,000mol/min for the whole course
Comparison
None
Outcome
With a median follow-up of 36.4 (range 2.9-51.5) months, 100-day, 1-year and 3-year non-relapse mortality was 3.8% (95%CI, 0-8.1%), 8% (95%CI, 2-14%), and 9.3% (95%CI, 2.6-15.9%), without a significant difference by age or HCT-CI score. One-year and 3-year relapse incidence was 10% (95%CI, 4-17%) and 18% (95%CI, 9-27%), respectively. Three-year overall survival was 80% (95%CI, 72-90%) and was similar for patients >60 and <60 years of age, as well as those with HCT-CI>3 and HCT-CI<3.
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Younger Haploidentical Donor Versus Older Matched Unrelated Donor for Patients With AML/MDS
Marcoux, C., Marin, D., Ramdial, J., AlAtrash, G., Alousi, A. M., Oran, B., Kebriaei, P., Popat, U. R., Rezvani, K., Champlin, R. E., et al
American journal of hematology. 2023
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Editor's Choice
Abstract
Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with older MUDs. Therefore, we performed a retrospective analysis comparing outcomes of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients who underwent HCT with younger (≤35 years) haploidentical donors (n = 494) or older (>35 years) MUDs (n = 1005). Patients in the haploidentical and MUD groups received post-transplant cyclophosphamide (PTCy) and conventional graft-versus-host-disease (GVHD) prophylaxis, respectively. In multivariate analysis, use of younger haploidentical donors was associated with improved overall survival (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.95, p = 0.01) and lower rates of grade II-IV acute GVHD (HR 0.64, 95%CI 0.53-0.77, p < 0.001), grade III-IV acute GVHD (HR 0.37, 95%CI 0.25-0.53, p < 0.001), and chronic GVHD (HR 0.49, 95%CI 0.40-0.60, p < 0.001). Relapse rates were similar among those who received myeloablative conditioning but were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18-1.88, p = 0.001). The younger haploidentical group had significantly lower non-relapse mortality ≥3 months post-HCT (HR 0.59, 95%CI 0.38-0.90, p = 0.02). Our data support the use of younger haploidentical donors with PTCy over older MUDs with conventional prophylaxis in patients with MDS or AML. Further studies on the importance of donor age in haploidentical and MUD HCT with PTCy prophylaxis are warranted. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Adults with myelodysplastic syndrome or acute myeloid leukemia undergoing transplant between 2008 and 2017, and reported to the CIBMTR registry (n=1499)
Intervention
Younger (</=35 years) haploidentical donor transplantation, with post-transplant cyclophosphamide GvHD prophylaxis (haploidentical group n=494)
Comparison
Older (>35 years) matched unrelated donor transplantation, with conventional GvHD prophylaxis (MUD group, n=1005).
Outcome
In multivariate analysis, use of younger haploidentical donors was associated with improved overall survival (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.95) and lower rates of grade II-IV acute GVHD (HR 0.64, 95%CI 0.53-0.77), grade III-IV acute GVHD (HR 0.37, 95%CI 0.25-0.53), and chronic GVHD (HR 0.49, 95%CI 0.40-0.60). Relapse rates were similar among those who received myeloablative conditioning but were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18-1.88). The younger haploidentical group had significantly lower non-relapse mortality ≥3 months post-HCT (HR 0.59, 95%CI 0.38-0.90).
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10.
Impact of Type of Induction Therapy on Outcomes in Older Adults with AML after Allogeneic Stem Cell Transplantation
Short, N. J., Ong, F., Ravandi, F., Nogueras Gonzalez, G. M., Kadia, T. M., Daver, N. G., DiNardo, C. D., Konopleva, M. Y., Borthakur, G., Oran, B., et al
Blood advances. 2023
Abstract
Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed post-HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC, n=44), lower-intensity therapy (LIT) without venetoclax (n=29) or LIT with venetoclax (n=54) and who underwent allogeneic HSCT in first remission. The 2-year relapse-free survival with LIT with venetoclax was 60%, versus 54% with IC and 41% with LIT without venetoclax, and 2-year overall survival for LIT with venetoclax was 72%, versus 58% with IC and 41% with LIT without venetoclax. The benefit to LIT with venetoclax induction was greatest in patients with adverse-risk AML (2-year OS 74%, 46%, and 29%, respectively). Induction with LIT, with or without venetoclax, was associated with the lowest rate of non-relapse mortality (NRM) (2-year NRM 17% versus 27% with IC; P=0.04). By multivariate analysis, type of induction therapy did not significantly impact any of the post-HSCT outcomes evaluated; hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was the only factor that independently predicted for RFS and OS. LIT plus venetoclax followed by HSCT is feasible treatment strategy in older, fit, and HSCT-eligible patients with newly diagnosed AML and may be particularly beneficial in those with adverse-risk disease.