Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial.
Leukemia relapse is a major cause of treatment failure for patients with acute leukemia given allogeneic bone marrow transplantation (BMT). This study evaluated whether a reduction of the dosage of cyclosporine-A (Cs-A) used for graft versus host disease (GVHD) prophylaxis could reduce relapse rate (RR) in children with acute leukemia given BMT. Fifty-nine children who had transplantation from HLA-identical siblings were randomized to receive Cs-A intravenously at a dosage of 1 mg/kg/d (Cs-A1) or of 3 mg/kg/d (Cs-A3) until patients were able to tolerate oral intake. Subsequently, both groups received Cs-A orally at a dosage of 6 mg/kg/d, with discontinuation 5 months after BMT. The probability of developing grade II-IV acute GVHD was 57% for the Cs-A1 group versus 38% for the Cs-A3 group (P =.06); the probability of developing chronic GVHD was 30% for the Cs-A1 group and 26% for the Cs-A3 group (P = NS). Three patients died of grade IV acute GVHD: 2 were in the Cs-A1 and the third in the Cs-A3 group. The RR was 15% for the Cs-A1 group and 41% for the Cs-A3 group (P =.034); 1-year transplant-related mortality estimates were 17% and 7%, respectively (P = NS). With a median observation time of 44 months from BMT, the 5-year event-free survival for children belonging to Cs-A1 and Cs-A3 groups was 70% and 51%, respectively (P =.15). Our data demonstrate that the use of low Cs-A doses is associated with a statistically significant reduction of leukemia relapse, probably due to an increased graft versus leukemia effect. (Blood. 2000;95:1572-1579)
Locatelli
F
F
Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy. f.locatelli@smatteo.pv.it
Zecca
M
M
Rondelli
R
R
Bonetti
F
F
Dini
G
G
Prete
A
A
Messina
C
C
Uderzo
C
C
Ripaldi
M
M
Porta
F
F
Giorgiani
G
G
Giraldi
E
E
Pession
A
A
D000208:Acute Disease; D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000187:drug effects; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007223:Infant; D007558:Italy / Q000453:epidemiology; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control*; D009679:Nuclear Family; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D011446:Prospective Studies; D012306:Risk; D014019:Tissue Donors; D019172:Transplantation Conditioning; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine