Should elderly patients with higher-risk myelodysplastic syndromes undergo allogeneic hematopoietic stem cell transplantation?

Abstract

Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies characterized by dysplastic changes, ineffective hematopoiesis and variable risk of leukemic progression. At diagnosis, 86% of MDS patients are ≥60 years. Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients, adds a median of only 9.5 months to life. Allogeneic stem cell transplantation (alloSCT) remains the only potentially curative approach. Despite recent improvements including use of reduced intensity conditioning (RIC) that decrease transplant-related mortality, alloSCT continues to be used rarely in elderly MDS. There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS patients, especially in direct comparison with azanucleosides. In this paper, the authors discuss the recent Markov decision analysis by Koreth et al. in which investigators demonstrated superior survival of patients with HR-MDS aged 60–70 years who underwent RIC alloSCT in comparison with those who were treated with azanucleosides.

Getting personal with myelodysplastic syndromes: is now the right time?

“…Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for MDS and the decision to proceed with HSCT is usually guided by the risk assessment to predict whether survival benefit outweighs the numerous risks associated with HSCT. Appropriate timing of HSCT is also paramount as delays can preclude the candidacy (88)(89)(90)(91).…”

A call for action: Increasing enrollment of untreated patients with higher‐risk myelodysplastic syndromes in first‐line clinical trials

“…After all, the only other treatment that can potentially prolong survival, and even lead to cure in some patients, is allogeneic hematopoietic stem cell transplantation (alloHSCT). 13 Many of the few patients who are cured with alloHSCT continue to experience long-term sequelae, including chronic graft-versushost disease and immune compromise, which could worsen quality of life and shorten life expectancy. 12 This means that the other >90% of patients with MDS are treated with noncurative therapeutic paradigms, including the use of HMAs, to palliate symptoms or attempt to prolong survival.…”

“…Even among the minority of individuals who do undergo alloHSCT, the outcomes are far from optimal, with long-term disease-free survival probabilities of only 30% to 40% due to high rates of disease recurrence and transplantation-related mortality. 13 Many of the few patients who are cured with alloHSCT continue to experience long-term sequelae, including chronic graft-versushost disease and immune compromise, which could worsen quality of life and shorten life expectancy. 14 The "lower-intensity" nature of HMAs, the feasibility of outpatient administration, and the recommendation by all clinical guidelines of HMAs as front-line therapy for untreated patients with HR-MDS all have led to the widespread use of HMAs in the community in the United States.…”

Platelet count doubling after the first cycle of azacitidine therapy predicts eventual response and survival in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukaemia but does not add to prognostic utility of the revised IPSS

“…Only 50–60% of patients achieve objective responses with azacitidine therapy, and prolonged treatment of 4–6 months is required before a failure to achieve a response can be declared (Silverman et al , , ; Fenaux et al , ). Additionally, almost all patients who respond to azacitidine will eventually progress, the majority within 2 years, and no cures are achievable with the drug (Zeidan & Gore, ; Zeidan et al , ). Once primary or secondary resistance to azacitidine occurs, the survival is dismal with a median OS of <6 months (Prebet et al , ).…”