Relapse following allo-HSCT remains frequent and represents an ongoing therapeutic challenge for patients with myelofibrosis or BP-MPNs.
Data from a retrospective analysis highlighted the ongoing challenges associated with post-transplant relapse in patients with myelofibrosis or blast-phase myeloproliferative neoplasms (BP-MPNs) undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT), along with potential approaches to improve outcomes for this patient population.1
The analysis, presented at the
Additionally, 17% of patients experienced molecular relapse at a median of 6.3 months (range, 1.6-32.9) following administration of allo-HSCT, with 6 of 8 patients encountering molecular relapse within the first year of transplant. Notably, a decline in donor chimerism was reported in all instances of molecular relapse. Three patients experienced molecular remission during calcineurin inhibitor prophylaxis; however, discontinuation of this therapy did not lead to molecular remission in any patients. In patients who experienced molecular relapse, 4 had JAK2 mutations, 3 harbored CALR mutations, and 1 had an MPL mutation.
Among the 8 patients who experienced molecular relapse, 7 received donor lymphocyte infusion (DLI), with a mean of 2 DLI infusions (range, 1-3) at doses ranging from 1 x 106/kg to 1 x 107/kg. Graft-vs-host disease occurred in 4 patients and led to DLI discontinuation. Molecular remission was reported in 4 patients undergoing DLI, who were free from molecule relapse at data cutoff. Three patients who received DLI progressed to hematologic relapse. In responders to DLI, 1 had a JAK2 mutation, 2 had CALR type 1–like mutations, and 1 had an MPL mutation. In nonresponders, 2 had JAK2 mutations, and 1 had a CALR type 2–like mutation.
Overall, hematologic relapse occurred in 11% of patients at a median of 21.4 months (range, 2.7-53.9) following allo-HSCT, including 2 patients with myelofibrosis and 3 with BP-MPNs. Three patients experienced molecular relapse prior to hematologic relapse, and they received treatment for low-risk myelofibrosis. The other 2 patients relapsed with aggressive BP-MPNs and died shortly following hematologic relapse.
Post-Transplant Relapse Outcomes in Myelofibrosis/BP-MPNs: Retrospective Data
“Post-transplant relapse remains relatively frequent and represents a significant therapeutic challenge,” lead study author Giacomo Coltro, MD, of Azienda Ospedaliero-Universitaria Careggi in Florence, Italy, and colleague wrote in a poster presentation of the data. “DLI appears to be an effective option in patients with molecular relapse, particularly in those carrying driver mutations traditionally associated with better post-transplant outcomes and potentially more ‘antigenic.’ The latter aspect is especially compelling in light of emerging targeted therapies, such as [anti–CALR mutation] monoclonal antibodies, which may further broaden therapeutic strategies and open promising avenues for managing post-transplant relapse.”
The retrospective, single-center study was intended to assess the incidence, timing, and clinical outcomes of post-transplant relapsed in patients with MPNs undergoing allo-HSCT. Although transplant remains the only potential curative-intent therapy for this patient population, post-transplant disease recurrence occurs in approximately 10% to 45% of patients across the MPN continuum, based on disease phase, molecular profile, and transplant-related factors.1-3
Investigators identified 47 patients who had a median age of 59.8 years (range, 41.9-69.6), and 38% of the population was female.1 All patients underwent allo-HSCT using peripheral blood stem cells, with 85% of patients received reduced-intensity conditioning.
Donor types included HLA-matched unrelated donors (62%), haploidentical donors (23%), and identical sibling donors (13%).
Study authors underscored the limitations of the study, noting its retrospective nature and small cohort size, and called for further investigations into outcomes and therapeutic approaches for this patient population.
