Myelofibrosis and stem cell transplantation: which factors correlate with better survival?

May 2020 Prevention Eline Feenstra
Stem cells operation. Health care concept. Surgeons team working. Bone marrow transplant operation. Plasma in syringe. Selective focus. Medical room background.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrose. Considerable research has been conducted to identify baseline risk factors that might predict transplantation results, such as patient age or comorbidities. However, there is scarce information regarding the influence of posttransplantation events, such as graft failure or graft-vs.-host disease (GVHD), on the outcome of MF patients after allo-HCT. A new study recently published in Nature, aimed to evaluate the determinants of survival in myelofibrosis patients undergoing allo-HCT and to describe factors predicting the main post-HCT complications.

This retrospective study by the European Society for Blood and Marrow Transplantation included 2.916 myelofibrosis patients who underwent first allo-HCT from an HLA-identical sibling or unrelated donor between 2000 and 2016. After a median follow-up of 4.7 years from transplant, projected median survival of the series was 5.3 years. Factors independently associated with increased mortality were age ≥ 60 years (HR: 1.45, 95% CI: 1.30–1.61; p <0.001), occurrence of graft failure (HR: 2.30, 95 % CI: 1.98–2.68; p <0.001), grades III–IV acute graft-vs.-host disease (aGVHD) (HR: 2.95, 95% CI: 2.59–3.36; p <0.001), and disease progression/relapse during follow-up (HR: 3.78, 95% CI: 3.33–4.28; p <0.001).

Predictors post-HCT events

Graft failure increased in unrelated donor recipients (SHR: 1.54; 95% CI: 1.17–2.03, p = 0.002) and decreased with myeloablative conditioning (MAC) and negative donor/recipient cytomegalovirus serostatus (SHR: 0.61; 95% CI: 0.46–0.81, p = 0.001; and SHR: 0.65; 95% CI: 0.41–0.81, p = 0.005). Risk of grades III–IV aGVHD was higher with unrelated donors (SHR: 1.45; 95% CI: 1.13–1.86; p <0.001) and decreased with MAC (SHR: 0.55 95% CI: 0.42-0.73; p <0.001) . Relapse incidence tended to be higher in patients with intermediate-2/high-risk DIPSS categories (SHR: 1.57; 95% CI: 1.00–2.46; p = 0.05) and to decrease in CALR-mutated patients (SHR: 0.56; 95% CI: 0.31–1.01; p = 0.055). Acute and chronic GVHD reduced the subsequent risk of relapse (HR: 0.80, 95% CI: 0.72-0.89, p = 0.001, and HR: 0.65, 95% CI: 0.58 – 0, 72; p = 0.001).

In conclusion, this study delineates the prognostic impact and predictive factors for the main complications after transplant in MF patients. This information might prove useful in patient counseling and clinical decision-making, particularly when trying to improve outcomes by personalizing the transplantation procedure.

Source

Nature