Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?

• Published in: Blood Vol. 144; no. 4; pp. 445 - 456
• Main Authors: Scheid, Christof, Eikema, Diderik-Jan, van Gelder, Michel, Salmenniemi, Urpu, Maertens, Johan, Passweg, Jakob, Blaise, Didier, Byrne, Jennifer L., Kröger, Nicolaus, Sockel, Katja, Chevallier, Patrice, Bourhis, Jean Henri, Cornelissen, Jan J., Sengeloev, Henrik, Finke, Jürgen, Snowden, John A., Gedde-Dahl, Tobias, Cornillon, Jérôme, Schanz, Urs, Patel, Amit, Koster, Linda, de Wreede, Liesbeth C., Hayden, Patrick, Raj, Kavita, Drozd-Sokolowska, Joanna, Gurnari, Carmelo, Onida, Francesco, McLornan, Donal P., Robin, Marie, Yakoub-Agha, Ibrahim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.07.2024
• Subjects: Adult; Aged; Female; Hematopoietic Stem Cell Transplantation - methods; Humans; Male; Middle Aged; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - pathology; Myelodysplastic Syndromes - therapy; Neoplasm Staging; Prognosis; Retrospective Studies; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023022273

•Changes in IPSS-R score between diagnosis and transplantation did not affect transplant outcome when no prior therapy was applied.•Downstaging IPSS-R by chemotherapy improved transplant outcome, however stable or worse IPSS-R after therapy correlated with worst outcome. [Display omitted] In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients. Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelodysplastic neoplasms, but whether to use conventional therapies before HCT is controversial. Scheid et al present a retrospective analysis examining whether changes in the revised International Prognostic Scoring System (IPSS-R), with or without treatment before HCT, influence outcomes. In the absence of therapy, changes in IPSS-R did not alter outcomes. While downstaging IPSS-R by chemotherapy correlated with improved transplant outcome, that was not the case for hypomethylating therapies, and stable or worse IPSS-R after therapy correlated with worse outcome. The created model can inform decisions by patients and physicians and suggests that pre-HCT therapy is not appropriate for many patients.