Haploidentical Transplant for Myelofibrosis: A Single Institution Experience

Background Myelofibrosis (MF) is a chronic hematologic malignancy with poor prognosis for which the only curative therapy is allogeneic stem cell transplant (alloHSCT). It is suggested that eligible patients with Intermediate-2 and high-risk disease proceed to transplant. Frequency of transplant for MF is increasing, given the advent of reduced intensity conditioning regimens and earlier identification of high-risk disease with mutation testing. Patients with MF are at high risk of regimen related toxicities and poor transplant outcomes due to increased risk of prolonged engraftment and graft failure. These concerns may contribute to a greater reluctance to embrace alternative donor source allografts such as haploidentical (haplo) donors. Herein, we report a case series of patients with MF undergoing alloHSCT. Methods A retrospective analysis was performed on all patients having received a haploidentical HSCT at our institution. Results Three patients were identified as having received haplo HSCT for MF. All received a bone marrow graft. Median age was 57 (range 46-61). One patient had primary MF, one post-PV MF, and one post-ET MF. Risk category at time of transplant by DIPSS was Intermediate -2 in two patients, and high in one. Two of the three patients had a major ABO mismatch. All patients and donors were positive for CMV IgG. Mean cell dose was 2.07 × 10^6 CD34+/kg recipient body weight (range 1.65 × 10^6 to 3.19 × 10^6). All patients received busulfan/fludarabine/melphalan conditioning (one myeloablative dosing, two reduced intensity). Post-transplant cyclophosphamide on days +3 and +4, tacrolimus, and mycophenolate mofetil were used for GvHD prophylaxis in all cases. Median time to neutrophil engraftment was Day +22 (range 20-24), median time to platelet engraftment was 67 days (range 37 - > 70). All patients had complete donor chimerisms at Day +30. Recovery of marrow cellularity was delayed in all patients. All patients had CMV reactivation by PCR, one patient had CMV esophagitis. Infectious complications were common, including BK virus, C. difficile colitis, invasive pulmonary aspergillosis, and klebsiella bacteremia Two patients developed chronic GvHD; one with cGVH of eyes & mouth not requiring systemic therapy, one with cGVH of upper GI tract/mouth. All patients are currently off immunosuppression. All patients are alive at a median follow up of 1.5 years post-transplant (range 456-656 days). Discussion Our case series using a haploidentical donor source and busulfan/fludarabine/melphalan conditioning along with post-transplant cyclophosphamide for patients with MF demonstrates outcomes at least comparable to conventional donor source transplants for MF. While infectious complications and slightly prolonged engraftment were noted in the early transplant period, these can be overcome with aggressive supportive care.