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

Abstract

Patients and methods

From 1993 to 2001 thirty two children underwent bone marrow transplantation (BMT) for ALL (12 in I CR and 20 in II CR after early BM or BM/organ relapse). Except 2 syngeneic all other were HLA-identical siblings transplants. All patients (pts) were conditioned with FTBI 2×1,5 Gy for 4 days (total dose 12 Gy) with lung shielding (9 Gy) and 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 VP 60 mg/kg i.v (n = 11 in I CR and n = 9 in II CR), Pts in I CR have been given 1,1–4,9×10⁸ MNC/kg (med. 2,7×10⁸/kg), while pts in II CR 1,9–4,0×10⁸ MNC/kg (med. 2,7×10⁸/kg). For GvHD prevention 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” MTX +/− PRED in 8 pts (n = 3 in I CR and n = 5 in II CR). Two pts transplanted with syngeneic BM received no GvHD prevention. 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°− 80%, II° −4%; stomatitis I° −40%, II° −20%; hepatic toxicity I°− 28%; renal, bladder and cardiac toxicity I°− 4%) and no transplant related deaths occured (TRM=0%). Among 12 pts transplanted in I CR only one child relapsed 4 months from BMT, while remaining 11 pts are alive in CCR with a median follow-up of 33months (range 6 to 66 months) and 92% probability of 5-year EFS. Of 20 children transplanted in II CR 6 relapsed 1–14 months from BMT (median 6,5 months). Fourteen of them remain in CCR with a median follow-up 19,5 months (range 1 to 96 months) and 66% probability of 8-year EFS.

Conclusions

• 1.

  In children with ALL the FTBI-12 Gy-containing regimen is well tolerated without the life-threatening toxic complications.

• 2.

  FTBI-12 Gy-containing regimen demonstrates very good antileukemic efficacy for HR-ALL in I CR, but only limited for ALL in II CA.

• 3.

  3. In context of good tolerance of FTBI in a total dose of 12 Gy and its limited antileukemic efficacy in children with ALL in II CR the escalation of FTBI total dose from 12 Gy to 13,2 Gy appears to be justified in those children. Supported by grant KBN 4 PO5E 108 18.