Full chimerism effect of nonmyeloablative haploidentical stem cell transplantation in pediatric resistant acute myeloid leukemia patients: An evidence of graft versus leukemia

Abstract

HLA-mismatched bone marrow transplantation after myeloablative conditioning Uierapy has been limited by severe GVHD and graft failure. Sykes et al. reported mixed lymphohemopoietic chimerism and graft-versus-lymphoma effects after nonmyeloablative therapy and HLA-mismatched bone marrow transplantation (Lancet, 1999). We would like to investigate this procedure whether it is feasible in pédiatrie patients. Three resistant acute myeloid leukemia (AML; 1 M4, and 2 M7) patients underwent this procedure in our insitution. All 3 patients (pt) had relapsed AML after intensive chemotherapy and 1 (ft. 1) also with autologous stem cell transplantation. Before these transplants, Pt. 1 had 2nd CR, and Pt. 2. and 3 still had leukemic relapse. Conditioning regimen consisted of fludarabine 40 mg/m2/ day x 5 days, and busulfan 4 mg/kg/day x 2 days in Pt. 1. Pt. 2, and 3 had TBI150 cGy x 2 days, and thymic RT 400 cGy x 1 day (Pt. 2), and 700 cGy x 1 day (Pt. 3). All 3 Pts received ATG 20 mg/kg/day x 2 days before and 10 mg/kg/day x 2 days after stem cell infusion. Stem cells were collected by peripheral blood stem cell mobilization from all 3 donors and were given without manipulation to all pts.. GVHD prophylaxis consisted of cyclosporin and mycophenolate mofetil in all pts. HLA-matching demonstrated 2 antigens mismatch in all 3. Chimerism was studied by FISH analysis for XX/XY. Pt. 1 had grade II and Pt. 2 had grade I acute GVHD. Pt. 2 had leukemic blast 40% in her marrow prior to transplant. After her transplant, all leukemic blasts disappeared in bone marrow examination on day +15. This can demonstrated an evidence of graft versus leukemia effect with this procedure. At present, both Pt. 1, and 2 still remian in remission. Pt. 3 is receiving stem cell infusion. Therefore, we have not evaluated her outcome yet. This promising result can prove that this approach is feasible with acceptable toxicity in pédiatrie patients even high risk AML patients. Pi/Sex/Donor CD34xlOVkg Day Day Donor Chimerism (%): F/U time (days) ANC>500 P1020.0CO Bone mairow/T cell 1/M/mother 7 +9 +11 <lay+250: 98/95 270 2/F/iacher M +13 +16 day+105: 99/85 106 3/F/father N/A N/A N/A N/A N/A.