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Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study

Bone Marrow Transplantation volume 58, pages 769–776 (2023)Cite this article

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Abstract

Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT. Primary endpoints were 3-year overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Post-alloSCT OS did not differ between t-MDS and t-AML (20.1 vs. 19.6 months, P = 1), though t-MDS had a significantly higher 3-year RI compared to t-AML (45.1% vs. 26.9%, P = 0.03). In t-MDS, the presence of monosomy 5 (HR 3.63, P = 0.006) or monosomy 17 (HR 11.81, P = 0.01) pre-alloSCT were associated with higher RI. Complex karyotype was the only factor adversely influencing survival at all the timepoints. The inclusion of genetic information yielded 2 risk-categories: high-risk defined by the presence of pathogenic variants (PV) in (TP53/BCOR/IDH1/GATA2/BCORL1) and standard-risk (remainder of the patients) with 3-year post-alloSCT OS of 0% and 64.6%, respectively (P = 0.001). We concluded that while alloSCT was curative in a subset of t-MN patients, outcomes remained poor, specifically in the high-risk category. t-MDS patients, especially those with persistent disease pre-alloSCT were at increased risk of relapse. Disease-related factors at t-MN diagnosis were the most prognostic of post-alloSCT survival; utility of factors available later in the course, was incremental.

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Fig. 1: Survival of t-MN patients following allogeneic SCT.
Fig. 2: Pathogenic somatic mutation predicts survival following allogeneic stem cell transplant (alloSCT).
Fig. 3: Landmark analysis for overall survival startified by donor chimerism.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding authors upon reasonable request (devendra.hiwase@sa.gov.au or shah.mithun@mayo.edu).

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Acknowledgements

We are grateful to our patients and their families. MVS was supported by Paul Calabresi Program in Clinical/Translational Research at Mayo Clinic (K12CA090628); Leukemia Research Foundation New Investigator Award; and Bridget Kiely Clinician Career Development in Transplant Research. DKH was supported by Investigator Grant, NHMRC/MRFF and Cancer Australia. BioRender software was used to create Fig. 1a.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Anmol Baranwal, Syed Shah, Mark R. Litzow, William J. Hogan, Abhishek Mangaonkar, Hassan B. Alkhateeb & Mithun Vinod Shah

  2. William J. von Leibig Center for Transplantation, Mayo Clinic, Rochester, MN, USA

    Anmol Baranwal, Matthew Clark, Mark R. Litzow, William J. Hogan, Abhishek Mangaonkar, Hassan B. Alkhateeb & Mithun Vinod Shah

  3. Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia

    Rakchha Chhetri, David Yeung, Deepak Singhal, Alia Cibich, Peter Bardy & Devendra K. Hiwase

  4. University of Adelaide, Adelaide, SA, Australia

    Rakchha Chhetri, David Yeung, Deepak Singhal, Peter Bardy, Chung H. Kok & Devendra K. Hiwase

  5. Precision Medicine Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

    Rakchha Chhetri, David Yeung, Chung H. Kok & Devendra K. Hiwase

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Contributions

AB, MVS, and DKH designed the study; AB, RC, MC, DKH, and MVS collated the data; AB, RC, and CK performed the statistical analysis; AB, DY, MRL, WJH, AM, HBA, DS, AC, PB, DKH, and MVS contributed patients; AB drafted the manuscript and DKH and MVS edited the manuscript. Other authors edited the manuscript, and all agree to the final version of the manuscript.

Corresponding authors

Correspondence to Devendra K. Hiwase or Mithun Vinod Shah.

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Competing interests

MRL—Research funding (AbbVie, Astellas, Amgen, Actinium, Pluristem), Advisory board (Jaz, Omeros), Data monitoring committee (BioSight); DY—Research funding from BMS and Novartis, Honoraria from Novartis, Pfizer, Amgen, and Takeda; DKH—Membership on an entity’s Board of Directors or advisory committees (AbbVie, Novartis); MVS—Research funding to the institution (Abbvie, Celgene, Astellas, and MRKR Therapeutics). The other authors declare no competing interests.

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Baranwal, A., Chhetri, R., Yeung, D. et al. Factors predicting survival following alloSCT in patients with therapy-related AML and MDS: a multicenter study. Bone Marrow Transplant 58, 769–776 (2023). https://doi.org/10.1038/s41409-023-01970-0

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