EFFECTIVENESS OF ORAL RUXOLITINIB FOR ACUTE GVHD PROPHYLAXIS AFTER HAPLOIDENTICAL BONE MARROW TRANSPLANTATION IN PATIENTS WITH SEVERE APLASTIC ANEMIA: A PHASE Ⅱ,SINGLE-CENTER, SINGLECOHORT, PROSPECTIVE CLINICAL TRIAL
After long-term follow-up, overall survival (OS) and failure-free survival (FFS) of patients with severe aplastic anemia (SAA) who underwent haploidentical bone marrow transplantation (haplo-BMT) is almost equivalent to that of matched sibling donor bone marrow transplantation (MSD-BMT). However, the incidence of severe aGVHD is still high after haplo-BMT with ATG-based prophylaxis and it is a serious complication after BMT in SAA. The aim of the study is to investigate the effectiveness and adverse events of oral ruxolitinib for aGVHD prophylaxis after haplo-BMT in patients with SAA.
Yan Yang et al. enrolled 20 patients with SAA (median age, 13[range, 5–47] years), who underwent haplo-BMT from August 2021 to April 2023 with a written consent. Among them, 14 were newly diagnosed SAA, and 6 were NSAA-progressed into SAA. A conditioning regimen of FluBuCy combined with ATG was used in haplo-BMT for SAA. Stem cells were mobilized and harvested from bone marrow and peripheral blood of healthy donors.
Oral ruxolitinib was taken approximately 0.1mg/kg twice daily beginning on days -4 to +100, while it was initially increased to 0.2mg/kg twice daily in the original six patients from days +21 to 100 days. If no aGVHD was developed, ruxolitinib was tapered beginning days +100 after HSCT. Tacrolimus and MMF were beginning on days -9 for aGVHD prophylaxis.
All patients had achieved successful engraftment with a median time for neutrophil and platelet recovery were 10 days. Four out of twenty patients (20%) experienced grades I-II aGVHD within days +100 after HSCT, including one with aGVHD induced by donor lymphocyte infusion (DLI) after post-transplant lymphoproliferative disorder (PTLD) on day +68. None experienced grades III-IV aGVHD. The median time of follow-up is 14.2 months.
Three out of twenty patients (15%) developed cGVHD, among which each one had mild, moderate, and severe cGVHD, respectively, during the follow-up period. All these patients recovered after treatment and no GVHD-related deaths. 3 out of the 20 patients experienced secondary poor graft function (sPGF), all of which were caused by infection. EBV and CMV reactivation rates were 35% and 45%, respectively. Four patients (20%) were diagnosed with post-transplant lymphoproliferative disorder (PTLD) which was probably associated with EBV reactivation. Two out of the original six patients with oral ruxolitinib prophylaxis suffered with PTLD and none developed aGVHD, therefore the recommended dose of oral ruxolitinib was reduced to 0.1mg/kg twice daily. Ten patients (50%) experienced infections during BMT; three had pneumonia, two experienced sepsis, and one was caused by fungal infection in the central nervous system (CNS). As a result, three cases died eventually. Only one patient had oral mucositis. The 3-year overall survival (OS), GVHDfree failure-free survival (GFFS), and transplant-related mortality (TRM) were 84.7%,84.2%, and 15%, respectively.
The regimen of ruxolitinib combined with tacrolimus and MMF was effective for severe aGVHD prophylaxis and oral mucositis without engraftment influence. However, opportunistic infections as well as EBV reactivation associated with PTLD should be full of early awareness.