ALL R-87 protocol in the treatment of children with acute lymphoblastic leukaemia in early bone marrow relapse


Dr Fiorina Giona Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Via Benevento 6, 00161 Rome, Italy.


Seventy-three children with acute lymphoblastic leukaemia (ALL) in first bone marrow (BM) relapse, occurring within 30 months from complete remission (CR), were enrolled in an Italian cooperative study (ALL R-87 protocol). This treatment programme consisted of an induction phase with intermediate-dose cytarabine (IDARA-C) plus idarubicin (IDA) and prednisone (PDN), followed by a multidrug consolidation therapy and bone marrow transplant (BMT). 55/73 children achieved CR (75.3%); 15 (20.5%) failed to respond and three (4.2%) died during induction. The response rate was significantly higher for children with a first CR duration geqslant R: gt-or-equal, slanted12 months (P = 0.0005) and for those with a white blood cell (WBC) count at relapse <20 × 109/l (P=0.004). The estimated disease-free survival (DFS ± SE) at 82 months was 0.18 ± 0.05 for all responders, and 0.70 ± 0.14 for allotransplanted patients versus 0.05 ± 0.05 for those autografted (P = 0.001). The estimated probabilities of survival ± SE and event-free survival (EFS ± SE) at 83 months were 0.16 ± 0.07 and 0.13 ± 0.04, respectively, for all enrolled children. Univariate analysis showed that age <10 years at initial diagnosis and B-lineage immunophenotype favourably influenced both DFS (P = 0.001) and EFS probabilities (P = 0.0014 and P = 0.012, respectively), whereas a first CR duration geqslant R: gt-or-equal, slanted12 months and a WBC count at relapse <20 × 109/l were associated only with a better EFS rate (P = 0.026 and P = 0.004, respectively).

Our results show the efficacy of the IDA plus IDARA-C schedule used in the ALL R-87 protocol in high-risk relapsed ALL children. Allogeneic BMT proved effective for patients with an HLA sibling donor. In a multivariate analysis, age geqslant R: gt-or-equal, slanted10 years at initial diagnosis (P = 0.016) and WBC count at relapse geqslant R: gt-or-equal, slanted20 × 109/l (P = 0.048) were independently associated with a worse disease outcome.