Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction

Abstract

<p>Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is one of the key determinants of outcome in myelofibrosis (MF) and remains an important unmet need. In this retrospective single-centre study, we evaluated 35 consecutive patients with MF receiving allogeneic HSCT. At 30 days post-HSCT, full donor chimerism was achieved in 31 patients (88.6%). The median time to neutrophil engraftment was 16.8 (10–42) days and the median time to platelet engraftment was 26 (12–245) days. Four patients (11.4%) experienced primary graft failure. With a median duration of follow-up of 33 (1–223) months, with the 5-year overall survival (OS) and progression-free survival (PFS) were 51.6% and 46.3%, respectively. Relapse after HSCT (<em>P</em> < 0.001), leucocyte count ≥ 18 × 10⁹/L at HSCT (<em>P</em> = 0.003) and accelerated/blast phase disease at HSCT (<em>P</em> < 0.001) were significantly associated with worse OS. Age at HSCT ≥ 54 years (<em>P</em> = 0.01), mutated <em>ETV6</em> (<em>P</em> = 0.03), leucocyte count ≥ 18 × 10⁹/L (<em>P</em> = 0.02), accelerated/blast phase MF (<em>P</em> = 0.001), and grade 2–3 bone marrow reticulin fibrosis at 12 months post-HSCT (<em>P</em> = 0.002) were significantly associated with worse PFS. <em>JAK2</em>V617F MRD ≥ 0.047 [sensitivity 85.7%; positive predictive value (PPV) 100%; AUC 0.984; <em>P</em> = 0.001] at 6 months and <em>JAK2</em>V617F MRD ≥ 0.009 (sensitivity 100%; PPV 100%; AUC 1.0; <em>P</em> = 0.001) at 12 months were highly predictive of post-HSCT relapse. Inferior OS and PFS were significantly associated with detectable <em>JAK2</em>V617F MRD at 12 months (<em>P</em> = 0.003 and <em>P</em> = 0.0001, respectively).</p>