A Pilot Study for Haploidentical Transplant Using a Chemotherapy only Preparative Regimen eith T-Cell Depleted Haploidentical Transplant and Intensive Antibiotic Prophylaxis To Treat Advanced Leukemia Patients (pts).

We present preliminary data of haploidentical transplant for 12 patients (pts) with relapse of refractory acute leukemia using a chemotherapy only preparative regimen of 140 mg/m² Melphalan on day −8; 10 mg/kg Thiotepa on day −7; 160 mg/m² Fludarabine on days −6, −5, −4, −3; 1.5 mg/kg of rabbit ATG/day days −6, −5, −4, −3 and T-cell depleted peripheral blood progenitor cells, processed using the CliniMACS® device. All products had <1 x 10⁴ CD3+ T-cells/kg recipient body weight and needed a minimum of 5 x 10⁶ CD34+ cells/kg but preferably >1 x 10⁷ CD34+ cells/kg recipient body weight. Pts received: intensive PCP prophylaxis with bactrim and pentamidine prior to transplant and during pancytopenia; CMV prophylaxis with valcyte during the BMT prep and foscarnet while pancytopenic; and with ambisone for fungus. The last 4 pts enrolled were treated with cancidas prophylactically instead of ambisome. 10 of 12 pts engrafted (83%). 2 pts had protocol deviations and primary graft failure - 1 survived disease free and 1 relapsed. Median time to engraftment was 14 days (range, 9–26) to 500 neutrophils and 13 days to platelets 20,000 (range, 10–25). Among engrafting patients, two died within 100 days due to disease progression and multiple organ failure. Six-month overall survival is 50% (21–74). One year overall and progression-free survival is 33% (95% CI 10–59). 7 pts had disease relapse at a median of 10 months (range 2–13 months). Two of 10 pts who engrafted developed grade 1 acute graft-versus-host disease (GVHD) and 4/8 pts who engrafted and survived beyond day 100 had chronic GVHD. The 2 patients who engrafted and survived beyond 1 year post transplant had chronic GVHD. This report for haploidentical transplant demonstrates that a chemotherapy only preparative regimen achieved a high rate of engraftment. Infectious complications were minimal. 25% of patients survived progression free. If these results are sustained in a larger study, haploidentical transplant may offer hope of allogeneic transplant for every individual needing such therapy.