Low Dose Splenic Radiotherapy for Myeloproliferative Neoplasms prior to Allogeneic Hematopoietic Stem Cell Transplant.

Abstract

Myeloproliferative neoplasms including primary and secondary myelofibrosis (MF) are a rare spectrum of chronic myeloproliferative disorders in which nearly 90% of patients experience splenomegaly. Importantly, splenic radiotherapy (SRT) may be used in combination with allogeneic stem cell transplant (alloSCT) to improve symptoms related to splenomegaly, though there currently is no consensus SRT dose/fractionation protocol reported in the literature for use in combination with alloSCT. We sought to report our institutional experience utilizing low dose SRT prior to alloSCT in the post-Jakafi era. We performed a retrospective review of all patients diagnosed with MF at our institution from 2017-2022 who received reduced intensity alloHCT. Patients who underwent total lymphoid or body irradiation were excluded. Descriptive demographic and clinical characteristics of patients were summarized by means, medians, standard deviations, ranges and proportions as appropriate. We identified 39 patients with MF who underwent reduced intensity conditioning (RIC) consisting of fludarabine/melphalan in preparation for alloHCT (median age 64.5, 12/16 males, median follow up 21 months). 16 patients with Jakafi-resistant splenomegaly completed low dose SRT prior to transplant (median spleen size: 24.5cm) with a median dose of 5Gy delivered in 5 fractions. 3D conformal therapy was used for all patients. All patients completed the planned total radiation course without treatment break or dose limiting acute toxicity. Thrombocytopenia was the most reported toxicity (CTCAE v5.0; 2 patients experienced grade 1, 1 patient experienced grade 2). No patients experienced grade 3 or higher acute cytopenias nor required transfusion during radiotherapy. All patients successfully received alloHCT a median of 7 days (range: 2-11) after the completion of SRT with a 94% (15/16) engraftment rate. Median neutrophil recovery (ANC > 500 × 3 days) time was 18 days (range: 13-31); median length of hospital stay was 23 days (range: 20-129). Overall survival was 75% in the SRT cohort (12/16, 2 with persistent disease, 2 due to other causes). Symptom burden data was available for 14/16 patients; 79% (11/14) of patients reported improvement in symptoms associated with splenomegaly or reduction in splenic size on physical examination. In the largest reported experience of a low dose SRT only cohort to date, we observe low dose SRT is feasible, safe in combination with alloHCT with high engraftment rates, and may reduce symptoms related to splenomegaly thereby improving patient quality of life without compromising transplant related outcomes. A prospective study validating this protocol is currently underway.