Integrating functional marrow reserve and molecular risk improves prediction of post-transplant outcomes in HMA-treated myelodysplastic syndromes∗†
6 affiliations
- 1Section of Medical Oncology and Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT
- 2Harvard T.H. Chan School of Public Health, Boston, MA
- 3Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
- 4Department of Data Science, Dana-Farber Cancer Institute, Boston, MA
- 5Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, Stanford, CA
- 6Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Abstract
In patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) and proceeding to allogeneic hematopoietic stem-cell transplantation (alloHSCT), pretransplant risk assessment remains dominated by morphologic remission–based frameworks despite uncertain prognostic value in the transplant setting. We retrospectively analyzed 280 HMA-treated patients with MDS undergoing alloHSCT at DFCI and Moffitt between 2013-2021 to evaluate the predictive performance of IWG 2023 response criteria and to develop an alternative framework integrating functional marrow reserve (FMR) with baseline molecular risk. Progression-free survival (PFS) was the primary outcome. Median overall survival (OS) was 52 months, with 5-year PFS and OS of 43% and 48%, respectively. IWG 2023 response categories showed substantial overlap in outcomes, and assessment by composite complete remission status did not discriminate PFS (5-year PFS 46% vs 40%; P = .16). In contrast, preconditioning hemoglobin and platelet counts were strongly associated with outcomes, whereas marrow blasts and absolute neutrophil count were not. Recursive partitioning identified clinically relevant platelet and hemoglobin thresholds, enabling construction of FMR strata with markedly distinct 5-year PFS (70%, 40%, and 24% for favorable, intermediate and poor risk strata, respectively; P < .0001). Baseline IPSS-M independently predicted outcomes (5-year PFS 58%, 45%, and 29%; P = .003) and further refined prognostication when integrated with FMR. In multivariable analysis, the integrated IPSS-M/FMR model remained independently associated with PFS (hazard ration 3.00–8.31 across risk tiers; P < .004) and showed superior discrimination compared with IWG 2023 and classical transplant variables (PFS concordance index 0.676). These findings support an integrated framework that outperforms remission-based criteria for post-alloHSCT risk prediction in HMA-treated MDS.
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BibTeX
@article{aguirre2026integrating,
title = {{Integrating functional marrow reserve and molecular risk improves prediction of post-transplant outcomes in HMA-treated myelodysplastic syndromes∗†}},
author = {Luis E. Aguirre and Haesook T. Kim and Hany Elmariah and Stacey M. Frumm and Amar H. Kelkar and Vincent Ho and Mahasweta Gooptu and John Koreth and Roman M. Shapiro and Rizwan Romee and Sarah Nikiforow and Joseph H. Antin and Robert J. Soiffer and Shai Shimony and Marlise R. Luskin and Jacqueline S. Garcia and Evan C. Chen and Martha Wadleigh and Eric S. Winer and Richard M. Stone and Daniel J. DeAngelo and Najla Al Ali and David Sallman and Andrew Kuykendall and Kendra Sweet and Jeffrey E. Lancet and Eric Padron and Onyee Chan and Zhuoer Xie and Corey S. Cutler and Maximilian Stahl and Rami S. Komrokji},
journal = {Blood Neoplasia},
year = {2026},
month = jul,
doi = {10.1016/j.bneo.2026.100275},
url = {https://doi.org/10.1016/j.bneo.2026.100275},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Integrating functional marrow reserve and molecular risk improves prediction of post-transplant outcomes in HMA-treated myelodysplastic syndromes∗†
AU - Luis E. Aguirre
AU - Haesook T. Kim
AU - Hany Elmariah
AU - Stacey M. Frumm
AU - Amar H. Kelkar
AU - Vincent Ho
AU - Mahasweta Gooptu
AU - John Koreth
AU - Roman M. Shapiro
AU - Rizwan Romee
AU - Sarah Nikiforow
AU - Joseph H. Antin
AU - Robert J. Soiffer
AU - Shai Shimony
AU - Marlise R. Luskin
AU - Jacqueline S. Garcia
AU - Evan C. Chen
AU - Martha Wadleigh
AU - Eric S. Winer
AU - Richard M. Stone
AU - Daniel J. DeAngelo
AU - Najla Al Ali
AU - David Sallman
AU - Andrew Kuykendall
AU - Kendra Sweet
AU - Jeffrey E. Lancet
AU - Eric Padron
AU - Onyee Chan
AU - Zhuoer Xie
AU - Corey S. Cutler
AU - Maximilian Stahl
AU - Rami S. Komrokji
PY - 2026
DA - 2026/07/27
JO - Blood Neoplasia
DO - 10.1016/j.bneo.2026.100275
UR - https://doi.org/10.1016/j.bneo.2026.100275
AB - In patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) and proceeding to allogeneic hematopoietic stem-cell transplantation (alloHSCT), pretransplant risk assessment remains dominated by morphologic remission–based frameworks despite uncertain prognostic value in the transplant setting. We retrospectively analyzed 280 HMA-treated patients with MDS undergoing alloHSCT at DFCI and Moffitt between 2013-2021 to evaluate the predictive performance of IWG 2023 response criteria and to develop an alternative framework integrating functional marrow reserve (FMR) with baseline molecular risk. Progression-free survival (PFS) was the primary outcome. Median overall survival (OS) was 52 months, with 5-year PFS and OS of 43% and 48%, respectively. IWG 2023 response categories showed substantial overlap in outcomes, and assessment by composite complete remission status did not discriminate PFS (5-year PFS 46% vs 40%; P = .16). In contrast, preconditioning hemoglobin and platelet counts were strongly associated with outcomes, whereas marrow blasts and absolute neutrophil count were not. Recursive partitioning identified clinically relevant platelet and hemoglobin thresholds, enabling construction of FMR strata with markedly distinct 5-year PFS (70%, 40%, and 24% for favorable, intermediate and poor risk strata, respectively; P < .0001). Baseline IPSS-M independently predicted outcomes (5-year PFS 58%, 45%, and 29%; P = .003) and further refined prognostication when integrated with FMR. In multivariable analysis, the integrated IPSS-M/FMR model remained independently associated with PFS (hazard ration 3.00–8.31 across risk tiers; P < .004) and showed superior discrimination compared with IWG 2023 and classical transplant variables (PFS concordance index 0.676). These findings support an integrated framework that outperforms remission-based criteria for post-alloHSCT risk prediction in HMA-treated MDS.
SN - 2950-3280
ER -