Promising Survival Rates Observed With 3D Spleen Size Analysis, Fludarabine/Melphalan-Based HSCT in Myelofibrosis

In patients with myelofibrosis (MF), promising disease-free survival (DFS) and overall survival (OS) were observed with fludarabine (Fludara; Bayer) and melphalan (Evomela; Acrotech Biopharma)-based hematopoietic stem cell transplantation (HSCT), regardless of patient pretransplant spleen volume and corresponding 3D spleen volumetric analysis, according to new results published in Transplantation and Cellular Therapy.¹

Hematopoietic stem cell transplantation (HSCT) is curative for myelofibrosis, but can cause adverse outcomes with associated splenomegaly. | Image Credit: © somchai20162516 - stock.adobe.com

Splenomegaly is linked to extramedullary hematopoiesis, several clinical symptoms, and prognostic factors in patients with MF, making it one of the most significant manifestations of the disease. Given that various clinical data indicates larger spleen size is linked to a poorer prognosis, splenomegaly is a target of approved drugs for MF, including ruxolitinib (Jakafi; Incyte Corporation) and momelotinib (Ojjaara; GlaxoSmithKline). In various randomized clinical trials, patients who received these treatments reported significant spleen reduction responses, indicating their widespread effectiveness. Still, many patients may require HSCT as a curative therapy, in which splenomegaly is known to negatively impact outcomes such as relapse, engraftment, and OS.^1,2

The current investigators note that prior literature has been inconclusive on splenomegaly’s association with HSCT outcomes, which they postulate could be due to variability in methods of 2D spleen size measurement and differences in HSCT platforms. Furthermore, whether spleen size can serve as a true prognostic indicator of MF is not fully determined due to the difficulty of conducting spleen size assessments with 2D analysis. In the current trial, they sought to leverage 3D volumetric analysis to provide a more comprehensive analysis of baseline spleen volume and its association with HSCT outcomes in patients with MF. Patients enrolled in the trial received reduced-intensity conditioning therapy with fludarabine and melphalan.¹

In the retrospective trial, 121 patients with MF who underwent HSCT with fludarabine/melphalan conditioning between 2004 and 2023 at the City of Hope. Patients were also required to have CT or MRI imaging completed within 3 months prior to HSCT for use in 3D spleen volume assessment. The investigators stratified patients by pre-HSCT spleen volumes of less than 2000 cc or greater than 2000 cc, with over 2000 cc being considered massive splenomegaly. Outcomes sought after by the authors included OS, DFS, relapse, non-relapse mortality, and engraftment—these were measured for both the entire cohort and for each spleen size group.¹

At the initiation of HSCT, median patient age was 62 years (range: 25-75 years), and 81% were classified as intermediate-2/high-risk by the Dynamic International Prognostic Scoring System-Plus (DIPPS-plus), which is typically used in studies to determine the risk of progression from MF to other conditions. In an important note, 47% of patients had received prior Janus kinase inhibitor therapy.^1,3

Median pre-HSCT spleen volume was measured at 1179 cc. At a median follow-up point of 98.7 months, investigators observed a 5-year cumulative incidence of DFS, OS, relapse, and NRM at 68.6%, 74.7%, 15.3%, and 16%, respectively. Critically, pretransplant spleen size did not meaningfully correlate with any of the examined HSCT outcomes, including DFS, OS, relapse, NRM, or platelet engraftment, according to the study investigators, which they noted was contrary to previous reports.¹

These results indicate the effectiveness of 3D volumetric spleen analysis in combination with fludarabine/melphalan-based HSCT in patients with MF, and present the possibility of incorporating this procedure into future MF treatment guidelines.¹

REFERENCES

1. Xiao A, Haseeb R, Yang D, et al. Overcoming splenomegaly risks in myelofibrosis transplantation: The role of 3D volumetric analysis and fludarabine melphalan conditioning. Transplantation and Cellular Therapy. 2025;31(2):S130. doi:10.1016/j.jtct.2025.01.198

2. Song MK, Park BB, Uhm JE. Understanding splenomegaly in myelofibrosis: Association with molecular pathogenesis. Int J Mol Sci. 2018;19(3):898. doi:10.3390/ijms19030898

3. Halpern L. Risk scores using molecular data can better identify patients with primary myelofibrosis who benefit from HSCT. Pharmacy Times. Published February 7, 2025. Accessed March 12, 2025.