December 10, 2023
By Dibash Kumar Das, PhD
In a global effort involving collaboration among European, U.S., and Latin American medical centers, a breakthrough has emerged regarding the role of splenic irradiation as a preliminary treatment approach for patients with myelofibrosis anticipating hematopoietic cell transplantation (HCT).
This study, presented at the 65th ASH Annual Meeting and Exposition, sought to address the challenges posed by splenomegaly in the context of HCT for patients with myelofibrosis, as existing treatments like Janus kinase(JAK) inhibitors often yield incomplete responses or subsequent disease progression (Abstract 2152).
The research, comprising 52 patients globally with 71 percent diagnosed with primary myelofibrosis, 17 percent post-polycythemia vera, and 12 percent post-essential thrombocythemia myelofibrosis, aimed to examine the efficacy and safety of splenic irradiation in shrinking spleen size before HCT. The median age at HCT was 60 years, showcasing a diverse representation of the myelofibrosis population.
Prior to irradiation, patients were stratified based on the Dynamic International Prognostic Scoring System (DIPSS) risk category, where 20 percent fell into the intermediate-1, 52 percent in the intermediate-2, and 28 percent in the high-risk category. The study also delineated driver mutation statuses, revealing JAK2 in 44 percent, calreticulin (CALR) in 40 percent, MPL in 4 percent, and a triple-negative status in 12 percent of patients. Notably, a few patients (4) experienced portal vein thrombosis before undergoing irradiation.
Most patients (76%) had previously received ruxolitinib, while a minority (4%) had been treated with fedratinib. Moreover, a majority of patients (73%) underwent reduced intensity conditioning HCT, with 85 percent receiving transplants from matched related or matched unrelated donors.
The analysis demonstrated a median time of 2 weeks from irradiation to HCT, with a median spleen size of 23 cm before irradiation, assessed primarily through ultrasound (70%), CT scans (20%), and physical examinations (10%). The median total irradiation dose administered was 7 Gy, fractionated across a median of five sessions.
While splenic irradiation showcased a substantial reduction in spleen size pre-HCT, it was coupled with significant decreases in platelet and leukocyte counts. Interestingly, there was no direct correlation observed between spleen size and blood counts either pre- or post-irradiation, although higher platelet counts pre-irradiation were associated with elevated counts post-irradiation.
Post-irradiation, 90 percent of patients achieved neutrophil engraftment within a median of 18 days after HCT, while 81 percent achieved platelet engraftment within a median of 38 days. The median follow-up of the entire cohort was 2.7 years, revealing a promising 3-year overall survival rate of 66 percent, with a low cumulative incidence of relapse (11%).
However, the researchers highlighted that larger spleen size before irradiation, lower hemoglobin levels, CALR/MPL-unmutated driver mutation genotype, and the presence of portal vein thrombosis were significantly associated with worse survival outcomes, emphasizing the predictive value of these factors in determining patient prognosis. This multinational study sheds light on the pivotal role of splenic irradiation in the HCT algorithm for myelofibrosis patients with splenomegaly.
“While reducing spleen size significantly impacted overall survival and non-relapse mortality, relapse rates remained low. Additionally, lower hemoglobin levels and the presence of portal vein thrombosis at the time of irradiation emerged as key predictors of adverse outcomes,” noted study presenter Nico Gagelmann, Dr. med, Professor and Medical Director of the Department of Stem Cell Transplantation at the University Hospital Hamburg-Eppendorf, Germany.
The findings from this comprehensive study mark a significant stride toward optimizing treatment strategies and prognostic assessments for myelofibrosis patients undergoing HCT, paving the way for more tailored and effective therapeutic interventions in the future.
Dibash Kumar Das is a contributing writer.