Cui bono? Finding the value of allogeneic stem cell transplantation for lower-risk myelodysplastic syndromes

ABSTRACT

Introduction

The myelodysplastic syndromes (MDS) vary in their risk of disease progression; progression includes increasingly severe bone marrow failure, reclassification as acute myeloid leukemia (AML), and death. Prognostic tools guide recommendations for allogeneic stem cell transplantation (alloSCT), the only curative option. AlloSCT is typically reserved for patients with higher-risk MDS as defined by existing prognostic tools, although additional clinical and biological factors in lower-risk patients may influence this dogma.

Areas covered

This review discusses the current understanding of MDS risk stratification as it pertains to the use of alloSCT in subpopulations of MDS patients with a particular focus on the use of alloSCT in patients with lower-risk disease.

Expert commentary

Though high-quality data are lacking, some lower-risk MDS patients may benefit from alloSCT, which offers the only prospect of cure. Understanding the etiologic role and prognostic impact of recurring genetic events may improve existing risk stratification and become integral facets of prognostic schemata. The identification of additional factors influencing the prognoses of patients currently lumped together as ‘lower-risk’ will likewise improve the selection of MDS patients for early intervention or aggressive therapies such as alloSCT.

KEYWORDS:

• Allogeneic
• alloSCT
• ASCT
• low
• lower
• MDS
• myelodysplastic
• transplant

Article highlights

• Risk stratification tools for MDS, such as the IPSS, IPSS-R, or WPSS, though widely used and guideline-recommended, are inadequate.

• Irrefutable evidence for the prognostic significance of somatic mutations such as those in SF3B1, EZH2, RUNX1, ASXL1, and most importantly, TP53, support their imminent incorporation into existing risk stratification tools.

• Patients with lower-risk MDS are a heterogeneous population with varied frequencies of poor-risk mutations as well as other prognostic factors, such as the presence of marrow fibrosis, prior ESA or DNMTi failure, and transfusion status, or complications (e.g. iron overload)

• Some patients currently classified as having ‘lower-risk’ MDS with poor-risk features beyond those accounted for in IPSS or IPSS-R, may derive benefit from alloSCT.

Declaration of interest

NA Podoltsev consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib, and CTI biopharma; received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals, Kartos Therapeutics and received grant funding from Celgene. AM Zeidan received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics and has had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, and Takeda. SD Gore received research support from Celgene, Boehringer-Ingelheim and has consulted for AbbVie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.