Mucositis Following HSCT With Myeloablative TBI Based on GVHD Prophylaxis Regimen

Abstract

Total body irradiation (TBI) is a commonly used preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT), however it is associated with severe mucositis, that frequently requires treatment with patient-controlled anesthesia (PCA) and parenteral nutrition (TPN). Severe mucositis is also a risk for infection and development of GVHD. Methotrexate (MTX), a drug commonly used for graft versus host disease (GVHD) prophylaxis, is also associated with mucositis. Newer GVHD prophylaxis regimens that avoid MTX, may reduce the incidence of severe mucositis after TBI based HSCT. We performed a retrospective analysis of all patients who underwent myeloablative HSCT with TBI (12 GY) and evaluated mucositis based on type of GVHD prophylaxis given. A total of 32 patients were identified, patients who received CSI (7) as part of their prep were excluded. 6 (24%) patients received MTX containing GVHD prophylaxis with 19 (76%) patients received post-transplant cyclophosphamide (PTCY) based GVHD prophylaxis. We compared severity of mucositis based on CTCAE v4, use of PCA, and use of TPN in these two groups. Secondary end points include length of post-infusion hospital stay, incidence of acute and chronic GVHD, transplant related mortality (TRM) at 30 and 100 days, and overall survival. The incidence of severe mucositis (grade ≥3) was lower in patients receiving PTCY (1/19) compared to MTX (5/6). Incidence of PCA and TPN use was also reduced in the cyclophosphamide (2/19 and 1/19, respectively) compared to MTX group (3/6 and 5/6, respectively). Expected rates of severe mucositis with TBI based conditioning would be 64%. All patients in the MTX group had a 10/10 HLA matched donor, with 1 unrelated donor. In the PTCY group, 6 patients had a 10/10 HLA matched related donor and 13 had a partial HLA match related donor. Patients with a partial HLA matched donor also received tacrolimus and mycophenolate mofetil (Cy/Tacro/MMF) as GVHD prophylaxis. Post-infusion hospital stay was shorter for MTX (19±5 days) compared to PTCY (24±8 days) group, but may reflect differences in stem cell source (100% of MTX were peripheral blood mononuclear cell (PBMC) compared to 32% of PTC patients). GVHD rates for MTX acute (1/6) and chronic GVHD (3/6) and Cy/Tacro/MMF (9/13 and 7/13, respectively) were consistent with previously reported rates, however rates with PTCY alone were unacceptably high (6/6 and 3/6, respectively). PTCY alone is no longer being used because of high GVHD rates. There was no transplant related mortality up to 100 days, 1 year data are still maturing. MTX sparing GVHD prophylaxis regimens reduce rates of mucositis associated with TBI based, myeloablative preparative regimens for HSCT.