Incidence of Mucositis and Effect on Outcomes with Myeloablative/Dose-Intensified Conditioning Regimens for HLA-Haploidentical Allotransplantation

Introduction Haploidentical allografts (Haplo) were originally performed using non-myeloablative conditioning (NMA) and marrow grafts. Data on mucositis when using Halpo with intensified and myeloablative regimens and PBSC grafts and post-transplant high-dose cyclophosphamide (ptCY) are not reported. Methods & Objectives We assessed 66 consecutive patients undergoing dose intensified Haplo at our center between 2018 and 2022. Patients received one of two dose-intensified regimens- 1) MAC - fludarabine 30mg/m2/d x 3d and TBI 1200cGy in 8 fractions over 4 days (n=52) 2) RIC – fludarabine 30mg/m2/d x 5 d and melphalan 140mg/m2 × 1d (n=14). All patients received a PBSC graft capped at 5 × 10e6 CD34 cells/kg followed by GVHD prophylaxis with standard ptCy (50mg/kg/d x 2 d), tacrolimus and MMF. Patients were managed as inpatients through d+5 for anticipated CRS and then discharged for outpatient management if well. Results Patient characteristics: median age 47 (20-64); male 61%; diagnosis -AML/MPS 65%, ALL30%, NHL 5%; DRI-low/intermediate 77%, high/very high 23%; HCT-CI (0-2) 45% >2) 55%; CMV pos 74%, donor: median age 31(15-70), relationship -sibling 39%, child 39%, parent 18%, other 3%; CMV pos 50%, Female to male 23%. Median follow-up was 33m (7-56). Thirty-three (50%) of patients developed mucositis requiring inpatient management (20% gd3) with median onset on d 7 (3-13). Median days on parenteral opiates and parenteral nutrition were 5 (0-11) and 3 (0-11) respectively. Median number of inpatient days during d0-30 was significantly greater for patients with mucositis vs no mucositis (16 d vs 11 d, p<0.001). However, the number of patients developing gram positive (27% vs 24%), gram negative (6% vs 6%), viral (30% vs 36%) and fungal infections (3% vs 6%) in d3-30 was not significantly different. Estimated 3-year survival, DFS, NRM, relapse and chronic GVHD and d 180 CI of acute GVHD gd 2-4 were not significantly different between patients with mucositis vs no mucositis. When comparing MAC to RIC, incidence (48% vs 57%) and severity (gd3- 19% vs 21%) of mucositis were not different. For MAC patients, gd 2-4 acute GVHD at d 180 was 72 vs 48% in patients developing mucositis vs no mucositis (p=0.09). Other outcome parameters were not significantly different for patients developing mucositis. Conclusions Half of patients receiving conditioning with either of the two intensified regimens combined with ptCy for Haplo develop clinically significant mucositis requiring inpatient management. While number of inpatient days were significantly longer for patients who develop mucositis, other outcomes were not worse.