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Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102
Saber, W., Bansal, A., Li, L., Scott, B. L., Sangaralingham, L. R., Thao, V., Roth, J. A., Wright, W., Steuten, L. M. G., Pidala, J. A., et al
JCO oncology practice. 2024;:Op2300413
Abstract
PURPOSE BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.
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Myeloablative Versus Reduced-Intensity Conditioning With Fludarabine/Busulfan for Myelodysplastic Syndrome: A Propensity Score-Matched Analysis
Kurosawa, S., Shimomura, Y., Itonaga, H., Najima, Y., Kobayashi, T., Ozawa, Y., Kanda, Y., Kako, S., Kawakita, T., Matsuoka, K. I., et al
Transplantation and Cellular Therapy. 2022;28(6):323.e1-323.e9
Abstract
There are limited data comparing myeloablative conditioning with fludarabine/busulfan (Flu/Bu4) and reduced-intensity conditioning with fludarabine/busulfan (Flu/Bu2) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data and compared the outcomes of adult patients with MDS receiving Flu/Bu4 and Flu/Bu2 by propensity score (PS) matching. Patients who met the following criteria were eligible for enrollment: (1) age ≥16 years; (2) diagnosis of de novo MDS; (3) first allo-HSCT between 2006 and 2018; (4) related bone marrow transplantation (BMT) or peripheral blood stem cell transplantation from an HLA-matched donor, unrelated BMT from an HLA-matched or HLA-1 allele-mismatched donor, or unrelated cord blood transplantation; and (5) receiving Flu/Bu4 or Flu/Bu2 as a conditioning regimen. Flu/Bu4 comprised intravenous busulfan (total dose, 12.8 mg/kg) combined with fludarabine (total dose, 125-180 mg/m(2)). Flu/Bu2 comprised intravenous busulfan (total dose, 6.4 mg/kg) combined with the same dose of fludarabine. To minimize selection bias and confounding factors, we performed a propensity score (PS)-matched analysis. The primary endpoint was overall survival (OS) after allo-HSCT. A total of 3386 patients with de novo MDS underwent their first allo-HSCT between 2006 and 2018. Among them, 202 patients were assigned each to the Flu/Bu4 and Flu/Bu2 groups after PS-matched analysis. The median age was 61 (interquartile, 57-65) years. The 3-year OS rates were 44.8% (95% confidence interval [CI], 37.1-52.1%) and 46.9% (95% CI, 39.2-54.2%) in the Flu/Bu4 and Flu/Bu2 groups, respectively (P = .67). The 3-year rates of graft-versus-host disease (GVHD)-free survival, relapse-free survival (GRFS) were 28.8% (95% CI, 22.2-35.7%) and 33.0% (95% CI, 26.2-40.0%), respectively (P = .36). The 3-year cumulative incidence rates of relapse were 28.9% (95% CI, 22.6-35.6%) and 30.0% (95% CI, 23.6-36.6%), respectively (P = .47). The 3-year cumulative incidence rates of non-relapse mortality (NRM) were 28.2% (95% CI, 21.7-35.0%) and 27.1% (95% CI, 20.6-33.9%), respectively (P = .60). The 100-day cumulative incidence rate of grade II-IV acute GVHD was significantly higher in the Flu/Bu4 group than in the Flu/Bu2 group (41.7% [95% CI, 34.8%-48.4%] versus 29.3% [95% CI, 23.2%-35.7%], P = 0.012). To identify patients who had more favorable outcomes with 1 of the 2 regimens, we compared the outcomes between the 2 groups after stratifying by age, hematopoietic cell transplantation-comorbidity index, cytogenetic risk, disease status at allo-HSCT, stem cell source, and donor type. OS, GRFS, relapse, and NRM did not differ between the 2 groups in any subgroup analyses. There were no significant interactions between the choice of conditioning regimens and any other factors. There are no differences in survival between Flu/Bu4 and Flu/Bu2, although our study population was highly selected by PS matching. Data from more patients and prospective studies are needed to determine the optimal intensity of conditioning regimens in patients with MDS.
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Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome
Nakamura, R., Saber, W., Martens, M. J., Ramirez, A., Scott, B., Oran, B., Leifer, E., Tamari, R., Mishra, A., Maziarz, R. T., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;:Jco2003380
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Editor's Choice
Abstract
PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined. METHODS We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration. RESULTS The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm (P = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; P = .003). The survival benefit was seen across all subgroups examined. CONCLUSION We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.
PICO Summary
Population
Patients with de novo myelodysplastic syndromes (MDS) aged 50-75 years (n=384)
Intervention
Allogeneic stem cell transplant: patients with an available donor within 90 days of registration (Donor arm, n=260)
Comparison
No transplant: patients with no donor available within 90 days of registration (No-Donor arm, n=124)
Outcome
The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% compared with 26.6% in the No-Donor arm with an absolute difference of 21.3%. Leukemia-free survival at 3 years was greater in the Donor arm (35.8%) compared with the No-Donor arm (20.6%). The survival benefit was seen across all subgroups examined.
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Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced-intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT
Shimoni, A., Robin, M., Iacobelli, S., Beelen, D., Mufti, G. J., Ciceri, F., Bethge, W., Volin, L., Blaise, D., Ganser, A., et al
British journal of haematology. 2021
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Editor's Choice
Abstract
Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n = 367), RIC (n = 687) or MAC (n = 668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively (P < 0·001) but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively, (P < 0·001). NRM was 30% (25-35), 27% (23-30) and 34% (31-38, P = 0·008), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively (P = 0·03). In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55, P < 0·001) and better OS (HR 0·72, P = 0·01). MAC was associated with higher NRM (HR 1·44, P = 0·001). In conclusion, FT is associated with similar low relapse rates as MAC and similar low NRM as RIC, resulting in improved OS. FT may be the preferred regimen for allo-HCT in MDS.
PICO Summary
Population
Patients reported to the EBMT registry with a diagnosis of myelodysplastic syndrome, receiving allogeneic transplant (n=1722)
Intervention
Fludarabine/treosulfan based conditioning (FT, n=367)
Comparison
Other reduced intensity conditioning regimens (RIC, n=687) or myeloablative conditioning (MAC, n=668)
Outcome
FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51 years, respectively but other disease characteristics were similar. The median follow-up was 64 months (1-171). Five-year relapse rates were 25% (21-30), 38% (34-42) and 25% (22-29), after FT, RIC and MAC, respectively. NRM was 30% (25-35), 27% (23-30) and 34% (31-38), respectively. Five-year OS was 50% (44-55), 43% (38-47), and 43% (39-47), respectively. In multivariate analysis, FT was associated with a lower risk of relapse (HR 0·55) and better OS (HR 0·72). MAC was associated with higher NRM (HR 1·44).
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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
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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.
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Comparison of non-myeloablative and reduced-intensity allogeneic stem cell transplantation in older patients with myelodysplastic syndromes
Jentzsch, M., Dohring, C., Linke, R., Hille, A., Grimm, J., Ponisch, W., Vucinic, V., Franke, G. N., Behre, G., Niederwieser, D., et al
American journal of hematology. 2019
Abstract
Allogeneic stem cell transplantation (HSCT) remains the only curative treatment for myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. The introduction of reduced intensity (RIC) and non-myeloablative (NMA) conditioning enabled HSCT in older or comorbid individuals representing the majority of patients. Studies comparing RIC and NMA conditioning are limited. We retrospectively analyzed 151 MDS or MDS/MPN patients older than 50 years who received NMA- or RIC-HSCT. Patients younger or older than 65 years at HSCT were analyzed separately. Patients receiving RIC-HSCT or NMA-HSCT were balanced in factors reflecting disease aggressiveness and the HCT-CI comorbidity score. NMA conditioned patients had a higher incidence of graft rejection and chronic graft-versus-host disease. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and overall survival (OS) did not differ significantly with regard to the conditioning regime in the whole cohort. In patients < 65 years at HSCT, NMA conditioning associated with higher NRM and shorter OS by trend while CIR was similar in both groups. In multivariable analyses, the conditioning regimen remained a prognostic factor for NRM and OS in patients < 65 years at HSCT. In MDS patients NMA and RIC conditioning result in similar disease control, but especially patients <65 years may benefit from RIC-HSCT. This article is protected by copyright. All rights reserved.
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A phase II multi-center study of the addition of azacitidine to reduced-intensity conditioning allogeneic transplantation for high-risk myelodysplasia (and older patients with acute myeloid leukemia: CALGB 100801 (Alliance)
Vij, R., Le-Rademacher, J., Laumann, K., Hars, V., Owzar, K., Shore, T., Vasu, S., Cashen, A., Isola, L., Shea, T., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Relapse remains the major cause of death in older patients transplanted for Acute Myeloid Leukemia (AML) in first complete remission (CR1) or for patients with advanced Myelodysplastic Syndrome (MDS) at any age. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with reduced intensity conditioning (RIC) when performed in younger patients with AML or MDS, but the toxicity of this approach in older patients is prohibitive. We hypothesized that pharmacokinetic targeting to optimize busulfan (BU) exposure, combined with the administration of azacitidine (AZA) post transplantation would mitigate the risk of relapse while reducing non-relapse mortality (NRM) and ultimately improve progression free survival (PFS). On this phase II multicenter study, 63 patients (40 unrelated donors (URD) and 23 matched related donors (MRD)) received a uniform conditioning regimen consisting of fludarabine IV (days -7 to -3), BU targeted to a daily area under the curve (AUC) of 4000uM*min (Days -6 to -3) following administration of a 25 mg/m2 intravenous test dose on one day between Days -14 to -9, and antithymocyte globulin (days -6, -5 and-4 (two doses for MRD and three for MUD only). Beginning day +42-+90, all patients were planned to receive up to six monthly cycles of AZA at 32mg/m2 subcutaneously x 5days. The median age was 62 years (44-74); 13 had AML and 50 had MDS. 87% of patients were within 20% of the target AUC based on a validation sample. A total of 41 patients (65%) started AZA at a median of 61 (range 43-91) days post-transplant, and 17(41%) of patients completed all 6 cycles of AZA. The cumulative incidence of non-relapse mortality (NRM) at 2 years was 33.4% (95% CI, 22% - 45%). The cumulative incidence of relapse was 25% (95% CI, 15%- 37%) at 2 years. With a median follow-up of 58.9 months, the estimated PFS probability at 2 years and 5 years after transplantation was 41.2% (80% CI, 33.9% - 49.9%) and 26.9% (80% CI, 20.4%-35.5%) respectively for the entire group with a median PFS of 15.8 (95% C.I, 6.7-28.3) mo. The OS probability at 2 and 5 years was 45.7% (95% CI, 34.9%-59.9%) and 31.2% (95% CI, 21.3% t- 45.8%) respectively for the entire group with a median OS of 19.2 (95% C.I. 8.7-37.5) mo. In summary, we demonstrated the feasibility of a novel RIC conditioning regimen with test dose BU targeted to an AUC of 4000uM*min. The feasibility of AZA in this setting appears limited if applied to an unselected population of older HSCT recipients. ClinicalTrials.gov Identifier: NCT01168219.
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Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial)
Kroger, N., Iacobelli, S., Franke, G. N., Platzbecker, U., Uddin, R., Hubel, K., Scheid, C., Weber, T., Robin, M., Stelljes, M., et al
Journal of Clinical Oncology. 2017;35(19):2157-2164
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Abstract
Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.
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Cytogenetics and comorbidity predict outcomes in older myelodysplastic syndrome patients after allogeneic stem cell transplantation using reduced intensity conditioning
Yucel, O. K., Saliba, R. M., Rondon, G., Ahmed, S., Alousi, A., Bashir, Q., Ciurea, S. O., Popat, U., Khouri, I., Marin, D., et al
Cancer. 2017;123(14):2661-2670
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with a curative potential for myelodysplastic syndrome (MDS) patients. Allo-HSCT has substantial risks, particularly in the elderly, and its role for older MDS patients has yet to be defined. METHODS We analyzed 88 MDS patients aged>=60 years with allo-HSCT after reduced intensity conditioning regimens over the last decade. The study cohort had high risk features; 47 of 88 (53.4%) patients were>65 years of age, 24 (27%) patients had cytogenetic abnormalities consistent with monosomal karyotype (MKpos), 33 (38%) patients had histological subtype of RAEB-1 and RAEB-2 at diagnosis, and 45 (51%) patients had a hematopoietic cell transplantation-comorbidity index (HCT-CI) of>=3. RESULTS The 3-year incidence of progression, transplant-related mortality (TRM), and overall survival (OS) were 26% (95% confidence interval [CI], 18%-37%), 35% (95% CI, 26%-47%), and 41% (95% CI, 30%-52%), respectively. MKpos was the only prognostic factor that increased the risk of disease progression compared with good-risk cytogenetics (hazard ratio [HR]=9.5, P=.003) as well as MKneg (HR=3.3, P=.01). For TRM, HCT-CI>=3, but not age >65 years, was associated with worse outcomes (HR=3.1, P=.007). Cytogenetics and HCT-CI enabled us to identify prognostic groups for OS. MKpos patients had the worst 3-year OS (17%), whereas patients with good-risk cytogenetics and HCT-CI<3 had the best OS (92%). CONCLUSION Our results confirm that allo-HSCT can provide long-term survival in older MDS patients. Cytogenetics and HCT-CI identify prognostic risk groups and guide selection of older MDS patients who are candidates for allo-HSCT. Cancer 2017;123:2661-70. © 2017 American Cancer Society.
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Non-myeloablative conditioning for lower-risk myelodysplastic syndrome with bone marrow blasts less than 5 %-a feasibility study
Choi, E. J., Lee, J. H., Lee, J. H., Kim, D. Y., Park, H. S., Seol, M., Lee, Y. S., Kang, Y. A., Jeon, M., Lee, K. H.
Annals of Hematology. 2016;95(7):1151-61
Abstract
Reduced-intensity conditioning (RIC) regimens can cause decreased non-relapse mortality (NRM) but lead to higher relapse rates in higher-risk myelodysplastic syndrome (MDS). However, relapse is not the main problem after hematopoietic cell transplantation (HCT) in lower-risk MDS, and post-transplant outcomes may therefore improve with less intense non-myeloablative conditioning (NMC) regimens. We here report the results of a single-center feasibility study of NMC with cyclophosphamide-fludarabine-antithymocyte globulin (CyFluATG) in MDS patients with bone marrow blasts <5 %. We compared post-transplant outcomes between CyFluATG and a RIC regimen, busulfan-fludarabine-antithymocyte globulin (BuFluATG). Fifteen MDS patients received allogeneic HCT after CyFluATG conditioning comprising cyclophosphamide (100 mg/kg), fludarabine (150 mg/m(2)), and ATG, and 30 MDS historical control patients received BuFluATG conditioning which contained busulfan (8 [oral] or 6.4 [i.v.] mg/kg), fludarabine, and ATG. The 4-year overall survival (OS) and NRM rates were 80.0 and 20.0 % for CyFluATG and 73.3 and 20.0 % for BuFluATG, respectively. Neutrophil and platelet engraftment was significantly faster with CyFluATG than BuFluATG (median 12 vs. 14 days, P=0.005 for neutrophils; median 15 vs. 21 days, P=0.032 for platelets). CyFluATG produced a faster immune reconstitution of T-cells at 1 month after HCT than BuFluATG. Fertility was maintained after HCT with CyFluATG. In conclusion, the CyFluATG regimen is feasible in lower-risk MDS patients in terms of adequate engraftment and low NRM.