Multiple Unit Umbilical Cord Blood Transplantation with Total Body Irradiation, Etoposide and Antithymocyte Globulin for Adult Hematologic Malignancy Patients.

Abstract 4344

Multiple unit umbilical cord blood transplantation (MU-UCBT) has become an acceptable alternative donor transplant approach for adult hematologic malignancy patients without a bone marrow or peripheral blood stem cell donor. Total body irradiation (TBI) and etoposide (VP16) is an effective conditioning regimen for allogeneic hematopoietic stem cell transplantation, but its utility in MU-UCBT has not been well described. From 10/03-2/09 16 adult hematologic malignancy patients were enrolled on a clinical trial at our institution using this regimen prior to MU-UCBT. Patients were eligible if they did not have an HLA matched related or unrelated donor. They also were required to have at least a 4/6 HLA matched UCB unit with at least 0.5 × 10⁷ nucleated cells/kg and a second UCB unit that was at least a 4/6 HLA match with the first UCB unit. The minimum required cryopreserved total nucleated cell (TNC) dose for the combined units was 1 × 10⁷/kg or an infused CD34+ cell dose of 1.5 × 10⁵/kg. Patients received TBI 1,320 cGy (fractionated over days -7 through -4), VP16 60 mg/kg (day -3) and antithymocyte globulin (ATG) 30 mg/kg (days -3 through +1). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. The median age was 47 yrs (range, 18-60) and diagnoses included: 8 AML, 3 CML-accelerated/blast phase, 2 MDS, 1 ALL, 1 CLL 1 NHL. Comorbidity index scores were 9 low, 6 intermediate and 1 high. The median time from diagnosis to UCBT was 8 mos (range, 1-89). HLA match results of the 1^st UCB unit infused (UCB1) with the recipient included five 4/6, ten 5/6 and one 6/6 matches, and for the 2^nd UCB unit (UCB2) with recipient there were one 3/6, five 4/6, and ten 5/6 matches. The median thawed TNC doses infused for UCB1 and UCB2 were 1.6 × 10⁷/kg (range, 1.0-2.4 × 10⁷/kg) and 1.2 × 10⁷/kg (range, 0.8-2.4 × 10⁷/kg), respectively; the thawed CD34+ cell doses were 0.6 × 10⁵/kg (range, 0.01-2.4 × 10⁵/kg) and 0.6 × 10⁵/kg (range, 0.2-3.1 × 10⁵/kg), respectively. Twelve were evaluable for engraftment analyses; 3 others had early deaths and 1 had graft failure and was rescued with infusion of cryopreserved remission autologous bone marrow. Sustained engraftment in the 12 was observed from a single UCB unit in all cases and the winning unit was UCB1 in 5 (42%). The winning unit had larger median CD8 (p=0.009) and thawed CD34+ cell (p=0.006) doses infused. The median time to achievement of T-cell complete donor chimerism was 30 days (range, 13-139). Median times to neutrophil and platelet engraftment were 20 days (range, 14-48) and 46 days (range, 29-86), respectively. Median time hospitalized was 39 days (range, 20-74). Grade 2-4 and 3-4 acute GVHD developed in 3 pts (19%) and 1 pt (6%), respectively. Chronic GVHD developed in 5 pts (31%) and 4 (25%) were extensive. Graft failure occurred in 2 pts. Six developed CMV infection and 15 developed other infections. There have been 2 (13%) relapses (1 MDS, 1 AML). Eight pts (50%) remain alive at a median follow-up of 15 mos (range, 5-35). Causes of death include 4 infections, 1 graft failure, 1 pulmonary toxicity, 1 CNS bleed, 1 relapse (AML). Incidence of death at 1 and 2 years are 45% (6% relapse, 39% non-relapse) and 59% (6% relapse, 53% non-relapse), respectively. We conclude that the TBI, VP16 and ATG conditioning regimen for MU-UCBT is effective in adult hematologic malignancy patients. Further strategies to enhance immune reconstitution and prevent infections post-transplant are clearly warranted.