Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings.
OBJECTIVE
Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-identical siblings can be used to treat children with acute lymphoblastic leukemia (ALL). However, a significant proportion of patients with ALL who undergo HSCT relapse. For this reason, we prospectively evaluated a preparative regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete remission (CR) and in children with ALL in second CR.


METHODS
Forty children (median age, 9 years; range, 1 to 18 years) with ALL in first or second CR who underwent allogeneic HSCT from HLA-identical siblings were conditioned with a combination of fractionated TBI, TT (10 mg/kg), and CY (120 mg/kg over 2 days). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine administered intravenously at a dose of 1 to 3 mg/kg/d for the first 21 days and subsequently orally at a dose of 6 mg/kg/d.


RESULTS
All assessable patients were engrafted, with a median time of 11 and 24 days for neutrophil and platelet recovery, respectively. The preparative regimen was well tolerated. Only one patient died as a result of regimen-related causes. Eight patients relapsed at a median time of 8 months after transplantation (range, 3 to 9 months), and this determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive and in complete hematologic remission, with a median observation time of 36 months (range, 14 to 57 months), which results in a disease-free survival (DFS) at 3 years of 65%. The 13 patients who underwent transplantation in first CR had a DFS of 85%, whereas the 27 patients who underwent HSCT in second CR had a DFS of 56%.


CONCLUSIONS
These data suggest that TT is an effective cytotoxic drug that can be safely added to the classical TBI-CY regimen. Because of its cell cycle-independent action, good CNS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.
Zecca
M
M
Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy. m.zecca@smatteo.pv.it
Pession
A
A
Messina
C
C
Bonetti
F
F
Favre
C
C
Prete
A
A
Cesaro
S
S
Porta
F
F
Mazzarino
I
I
Giorgiani
G
G
Rondelli
R
R
Locatelli
F
F
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005069:Evaluation Studies as Topic; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009679:Nuclear Family; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000628:therapy*; D011446:Prospective Studies; D012074:Remission Induction; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide; D013852:Thiotepa