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 children with high-risk first CR and 19 in second or subsequent CR lacking matched family allogeneic donors underwent ABMT with chemopurged bone marrow utilizing verapamil (VPL), vincristine, and VP-16. Patients were conditioned with TBI, VPL bolus and infusion with VP-16 and cyclophosphamide. The first cohort of patients (n = 4) received only cyclosporin A (CsA). The second cohort (n = 7) received CsA and alpha interferon (total = 11 with post-transplant immunotherapy alone.) The third cohort (n = 13) received CsA and six alternating cycles of alphaIFN and chemotherapy and six additional cycles 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 is 54+/-10% (90% CI is 37.5-70.5%). Furthermore, patients receiving PTIC (n = 13) vs immunotherapy alone (CsA+/-aIFN) (n = 11) had a substantially 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 ABMT with chemopurging, combined with PTIC is well tolerated and may be an alternative new approach in the treatment of a subset of children with high-risk first CR or > or = second CR ALL who lack closely matched family-related allogeneic donors.
Houtenbos
I
I
Division of Pediatric Oncology and Blood and Marrow Transplantation, Babies and Children's Hospital, Columbia University, New York, NY 10032, USA.
Bracho
F
F
Davenport
V
V
Slack
R
R
van de Ven
C
C
Suen
Y
Y
Killen
R
R
Shen
V
V
Cairo
M S
MS
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D020544:Graft vs Leukemia Effect; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007167:Immunotherapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine