My paper of the Month - Outcomes of allogeneic transplantation in blast-phase myeloproliferative neoplasms: one-third achieve long-term survival

Publication Full Title: Outcomes of allogeneic transplantation in blast-phase myeloproliferative neoplasms: one-third achieve long-term survival

Journal: Bone Marrow Transplantation

Published: 16 April 2026

DOI: 10.1038/s41409-026-02842-z

Publication Link: https://www.nature.com/articles/s41409-026-02842-z

Commented by: Dr James Dillon, Specialist Registrar in Haematology & Dr Chris Armstrong, Consultant Haematologist, St James’s Hospital, Dublin, Ireland.

Review

This paper by Barbullushi et al from Hamburg in Germany reports outcomes following allograft for blast phase Philadelphia-negative myeloproliferative neoplasms (Ph- BP MPN). Ph- BP MPN represents a family of overlapping disorders with an aggressive disease biology, a lack of standardised and effective treatment options and typically has a dismal prognosis, with a median overall survival of less than 6 months. Allograft is considered the most substantive treatment for high-risk aggressive myeloid malignancies, but due to disease rarity and lack of prospective studies, proving its efficacy and utility in Ph- BP MPN is challenging.

This study is a single centre retrospective analysis from University Medical Centre Hamburg-Eppendorf, Germany, which reviewed 53 allografts performed in adult patients for Ph- BP MPN between 2002 and 2020. The median age was 62 years and there were 14 second transplants included. Ph- BP MPN evolved from primary myelofibrosis (PMF) in over half of cases, with the remainder of cases evolving from polycythemia vera (PV), post-PV MF, essential thrombocythemia (ET) and post-ET MF. More than half of patients harboured a JAK2 driver mutation, with the remainder having CALR, MPL or triple negative disease. TP53 mutation status was available in 32/53 patients, with 3 cases of mutant TP53. 19 patients proceeded directly to transplant without induction treatment.

The primary outcome was overall survival (OS) and in this cohort durable long-term remissions in a subset of patients with Ph- BP MPNs were seen, with a 1-year and 5-year OS of 43.4% and 35.95% respectively at a median follow-up of 4.7 years. Relapse was the main cause of death with a cumulative incidence at 1 year of 44.3%. Non-relapse mortality was notable in the first year at 25.8%, with infection and graft versus host disease as the leading causes. The inclusion of 14 second allografts may have accounted for some of this reported toxicity.  

Perhaps the most practical finding was the identification of a correlation between circulating blasts at time of transplant and survival outcomes. Both the presence and proportion of circulating blasts were independently associated with inferior outcomes. Each 1% increase in peripheral blast percentage increased mortality risk by 3% (HR 1.03).  Interestingly, complete remission prior to transplantation was not independently associated with improved survival, which may support temporary debulking, rather than striving for complete morphologic remission as the more important determinant of post-transplant outcomes. Analogous to the story in CML, a return chronic phase may be the optimal goal, and indeed, even a return to accelerated phase is likely sufficient, as demonstrated by Gagelmann et al¹. 

In this study more than half of patients received induction chemotherapy, primarily with intensive regimes. Given the retrospective cohort nature of the study, there is no intention to treat population of patients who received induction, but then did not successfully make it to transplant, and so some questions remain. It is unclear in 2026 which induction therapy is optimal for this group of patients, if any.  Ph- BP MPN are frequently underrepresented in AML trials, although recent support for lower intensity approaches is encouraging, such as the recent PARADIGM trial, showing superior outcomes with azacitidine and venetoclax versus intensive chemotherapy in intermediate and high-risk AML, including secondary disease². However, in the largest study specifically of Ph- BP MPN by Anand et al, 65 patients of the total cohort of 202 patients went on to receive an allograft following induction and no difference in survival was identified in those who received intensive chemotherapy vs. hypomethylating agents +/- venetoclax³.

Sequential conditioning with FLAMSA did not improve OS in this study, albeit with interpretive caveats as these patients were likely in the highest risk subgroup, with a greater burden of active disease. The lack of benefit may reflect disease aggression, rather than conditioning itself; a point that the authors have identified already with circulating blasts predicting survival.

Unsurprisingly TP53 mutations were associated with a significantly inferior survival (HR 2.64), although mutation status was only available on 32 patients and only a small number were identified. While TP53 is not formally considered in risk calculation in chronic phase MF (e.g. MIPSS70v2), the implication of its presence when it comes to conventional chemotherapy-based conditioning therapy is likely significant, and a recurring motif across aggressive myeloid malignancies. A CALR mutation was associated with improved OS (HR 0.32), however in keeping with disease epidemiology, it was present in less than 20% of patients. Donor type and conditioning intensity did not appear to impact on outcomes; however, given the median age at transplant and the sample size, strong conclusions cannot be drawn from this.

The authors acknowledge several limitations, namely the retrospective, single centre nature of the study and the sample size. The median year of transplant was 2016 but included some patients from as early as 2002. There have been steady advances in many aspects of transplant medicine in the timespan included, such as donor selection, transplant conditioning, supportive care and recipient eligibility. Importantly in that period, JAK inhibitors, molecular diagnostics and risk stratification have evolved significantly in MPNs. Indeed, important work from this group on the role of molecular MRD monitoring and interpretation post-transplant are actively shaping how we conduct modern transplants for MPNs, and by extension BP-MPNs⁴.  

Limitations notwithstanding, this study represents one of the larger single centre studies examining the utility of allograft as a curative option for Ph- BP MPNs. The authors provide demonstrable evidence that allograft can result in durable long-term remissions in a not-insignificant proportion of patients with Ph -BP MPN, for whom survival without transplant is wholly unsatisfactory. Identifying those who are likely to do best based on peripheral disease burden may prove to be a useful clinical tool, although the dearth of therapies available to modulate this remains a challenge. To tackle the questions raised by this paper, the EBMT registry is well positioned to gather and describe multi-centre outcomes, collate modern molecular annotation and ultimately refine prognostication and optimise transplant outcomes for this uncommon disease group. In the meantime, this paper is useful to clinical transplanters when counselling patients with these diseases, allowing us to offer estimates of transplant success based on real-world results. 

References

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