Fludarabine/Busulfan Conditioning-Based Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis: Role of Ruxolitinib in Improving Survival Outcomes

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib before HCT (n = 32), and those with splenomegaly >22 cm received pretransplantation splenic irradiation. The median age at HCT was 60 years (range, 40 to 74 years), and 68% of the cohort carried a JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning; 22 patients (59%) received a reduced-intensity conditioning regimen. All patients received peripheral blood grafts, from a matched sibling donor in 16 patients (43%), an unrelated donor in 20 patients, and a haploidentical-related donor in 1 patient. Sixty-one percent had a Hematopoietic Cell Transplantation Comorbidity Index 3, 40% had a Karnofsky Performance Status score <90, and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9 to 115 months), the 3-year overall survival and relapse-free survival were 81.1% (95% confidence interval [CI], 64.4% to 90.5%) and 78.4% (95% CI, 61.4% to 88.5%), respectively. Only 2 patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5% to 29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplantation for graft-versus-host disease, graft rejection/relapse, or persistent MF. These results suggest that pretransplantation ruxolitinib, fludarabine/busulfan-based conditioning, and splenic management are keys to improved transplantation outcomes in patients undergoing allo-HCT for MF.

Effect of pre‐transplant JAK1/2 inhibitors and CD34 dose on transplant outcomes in myelofibrosis

“…33 We could not demonstrate any effect of pre-transplant JAKi on survival. Recent studies [38][39][40][41][42] have reported encouraging survival outcomes in MF patients who prior to transplantation is associated with improved outcomes. 44,45 We did not find any effect of splenectomy or spleen size on survival outcomes or engraftment times.…”

“…routinely received JAKi pre-transplant. One such report by Chhabra et al38 reported a 3-year OS of 81.1% and 3-year RFS of 78.4% in a cohort of 37 patients, and there were no primary graft failures. The authors postulated that the potential benefits of ruxolitinib in reducing GVHD, NRM, and relapse could be responsible for the improved survival.…”

Pretransplant Splenic Irradiation in Patients With Myeloproliferative Neoplasms

“…Please refer to a previous publication for additional information on the conditioning regimens used in these patients and the transplant outcomes. 18 As part of the protocol, patients with MPN with splenomegaly measuring greater than 22 cm were referred for splenic irradiation, with the final fraction completed 1 day before scheduled admission for conditioning.…”

Allogeneic Hemopoietic Stem Cell Transplantation for Myelofibrosis: 2021

“…Recently Chabra et al. published a small number of MF patients, mostly treated with ruxolitinb pre-transplant ( 71 ): after a median follow up of >3 years, two patients out of 37 had relapsed after HSCT (5.4%), but the study lacked a strong control group of untreated ruxolitinib patients. Indeed other recently published data in the ruxolitinib era ( 72 ), have shown no improvement in survival nor in the incidence of relapse for MF.…”