Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia: a novel combined approach consisting of ex vivo marrow purging, modulation of multi-drug resistance, induction of autograft vs leukemia effect, and post-transplant immuno- and chemotherapy (PTIC)

In an attempt to reduce the high relapse rate associated with ABMT, five ch ildren with high-risk first CR and 19 in second or subsequent CR lacking ma tched family allogeneic donors underwent ABMT with chemopurged bone marrow utilizing verapamil (VPL), vincristine, and VP-16, Patients were conditione d with TBI, VPL bolus and infusion with VP-16 and cyclophosphamide, The fir st cohort of patients (n = 4) received only cyclosporin A (CsA), The second cohort (n = 7) received CsA and alpha interferon (total = 11 with post-tra nsplant immunotherapy alone.) The third cohort (n = 13) received CsA and si x alternating cycles of alpha IFN and chemotherapy and six additional cycle s of chemotherapy (vincristine, VP-16, Ara-C, prednisone) followed by G-CSF (post-transplant immune chemotherapy (PTIC)), The 2-year DFS is 42 +/- 10% (90% confidence interval (CI) is 26.5-58.5%) and 2-year overall survival i s 54 +/- 10% (90% CI is 37.5-70.5%). Furthermore, patients receiving PTIC ( n = 13) vs immunotherapy alone (CsA a alpha IFN) (n = 11) had a substantial ly better 2 year DFS and OS: 69 +/- 13% vs 13 +/- 12% and 85 +/- 10% vs 25 +/- 15% (P = 0.008 and P = 0.06, respectively). These results suggest that the use of ABR IT with chemopurging, combined with PTIC is well tolerated a nd may be an alternative new approach in the treatment of a subset of child ren with high-risk first CR or greater than or equal to second CR ALL who l ack closely matched family-related allogeneic donors.