Allogeneic bone marrow transplantation in children with acute lymphoblastic leukaemia in the first and second complete remission conditioned with fractionated total body irradiation and cyclophosphamide or etoposide

Abstract

Patients and methods From 1993 to 2001 thirty-two children underwent bone marrow transplantation (BMT) for acute lymphoblastic leukaemia (ALL) (12 in I complete remission /I CR/of high-risk/HR/ALL, and 20 in II CR after early bone marrow or combined bone marrow/organ relapse). Except for two syngeneic all others were matched sibling donor transplants. All patients (pts) were conditioned with fractionated total body irradiation (FTBI) at a total dose of 12,6 Gy, given in 8 fractions during 4 days with lung shielding (9,4 Gy) and cyclophosphamide (CY) 60 mg/kg i.v for 2 days (total dose 120 mg/kg) (n = 1 in I CR and n = 11 in II CR) or etoposide (VP) 60 mg/kg i.v (n = 11 in I CR and n = 9 in II CR). Patients in I CR were given 1,1–4,9×10 8 nucleated cells /kg (med. 2,7×10 8/kg), while pts in II CR 1,9–4,0×10 8 nucleated cells/kg (med. 2,7×10 8/kg). For graft versus host disease (GvHD) prevention cyclosporin A (CsA) 3 mg/kg/d i.v was administered alone in 22 pts (n = 9 in I CR and n = 13 in II CR) or in combination with “short” methotrexate +/− prednisone in 8 pts (n = 3 in I CR and n = 5 in II CR). Two pts transplanted with syngeneic BM received no GvHD prevention. The regimen related toxicity (RRT) was graded according to the system developed by Bearman et al. (1988). Results Only mild or moderate expression of RRT was observed (GI toxicity I 0 – 80%, II 0 – 4%; stomatitis I 0 – 40%, II 0 – 20%; hepatic toxicity I 0 – 28%; renal, bladder and cardiac toxicity I 0 – 4%) and no transplant related deaths occurred (TRM = 0%). Among 12 pts transplanted in I CR only one child relapsed 4 months from BMT, while the remaining 11 pts are alive in continuous complete remission (CCR) with a median follow-up of 33 months (range 6 to 66 months) and 92% probability of a 5-year event free survival (pEFS). Of 20 children transplanted in II CR 6 relapsed 1–14 months from BMT (median 6,5 months). Thirteen of them remain in CCR with a median follow-up of 19.5 months (range 1 to 96 months) and with 66% probability of a 8-year EFS. Conclusions 1. In children with ALL the FTBI-12,6 Gy-containing regimen is well tolerated without life-threatening toxic complications. 2. The FTBI-12,6 Gy-containing regimen demonstrates very good antileukaemic efficacy for HR-ALL in I CR, but only limited efficacy for ALL in II CR. 3. In the context of good tolerance of FTBI in a total dose of 12,6 Gy and its limited antileukaemic efficacy in children with ALL in II CR the escalation of FTBI total dose from 12,6 Gy to at least 13,2 Gy appears to be justified in those children.