Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis
Key claim: In a phase II trial of reduced-intensity haploidentical HCT for primary or secondary myelofibrosis, pre-transplant JAK inhibitor use yielded universal engraftment with no graft failure but substantial GVHD, prompting a new cohort using JAK inhibitor before, during, and after transplant to reduce GVHD without raising graft-failure risk.
Abstract
This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.
Why this matters
Haploidentical donors dramatically expand the eligible transplant pool for MF patients who lack matched donors — directly relevant to the documented int-2/high-risk MF referral gap — but historically bring higher GVHD risk. This trial’s iterative design (universal engraftment with pre-transplant JAK inhibition, then extending JAK inhibition peri- and post-transplant to address GVHD) refines a haplo-RIC protocol that could make transplant a realistic option for a broader MF population.