CT-255: Progressive Substitution of Post-Transplant Cyclophosphamide with Bendamustine as GVHD Prophylaxis Reduces GVHD while Preserving GVL

Abstract

Context Post-transplant cyclophosphamide (PTCy) is approved in haploidentical stem cell transplant setting. However, disease relapse and CMV or BK/JC viral reactivation veno-occlusive disease of the liver (VOD) remains a major challenge with the use of PTCy. Progressive substitution of PTCy with bendamustine (PT-BEN) may be a suitable option as evidenced by murine models. Objective To compare the outcomes for patients receiving PTCy with PT-BEN compared to historical cohorts receiving PTCy alone. Design This is a single arm, retrospective and prospective, single centre study in which all the patients undergoing allogeneic stem cell transplantation with a T-cell replete graft were recruited. Patients or Other Participants All patients received T-cell replete stem cells followed by PTCy 50mg/kg on day +3 and bendamustine 90mg/m2 on day +4. Calcineurin inhibitors with mycophenolate mofetil was given. Main Outcomes Measures The main outcome measures included myeloid and platelet engraftment, viral reactivations, disease status, incidence and severity of acute GVHD, incidence of veno-occlusive disease until D+28 post-transplant. Results Five patients have been recruited, all males, median age being 17 years. Two patients had relapsed/refractory (R/R) ALL after 2 lines of therapy, 1 had R/R AML, 1 had very severe aplastic anemia, 1 was high risk ALL in CR1. 3 fully matched a sibling, whereas 2 had haplomatched donors from mother. All the donors and recipients had seropositivity for CMV. Two patients received FluCyTBI, 2 received FluCyATG, and 1 received FluTreoTBI as conditioning. One patient expired due to neutropenic septic shock on D+8 and has been excluded from analysis. The median day for myeloid engraftment was 12 and platelet engraftment was 14. No patient had VOD, thrombotic microangiopathy, or culture positive bacterial infections. All the patients were in CR, 100% donor chimerism at D+28. Three patients had CMV reactivation, controlled with antivirals. One patient had Gr1 skin GVH and 1 patient had Gr1 gut GVH managed with topical and oral steroids respectively. Conclusions Progressive substitution of PT-BEN may ameliorate the toxicities associated with PT-Cy in post-transplant setting.