The Role of Cranial Irradiation (CRT) or Extended Triple Intrathecal Therapy (T.I.T.) in Childhood T-Cell ALL; the ALL Israel National Studies (INS) 89 and 98 (Modified ALL-BFM 86 and 95) Report.

Patients with T-cell ALL are at increased risk of CNS relapse and require more intensive CNS directed therapy. CRT is considered to be the most effective therapy, but is associated with serious adverse late effects and secondary brain tumors. We evaluated retrospectively, in the context of the ALL-BFM-based protocols, the impact of CRT or extended T.I.T. on outcome within High Risk (HR: Prednisone poor responders) and non-HR (Prednisone good responders) subgroups.

In INS 89, modified ALL-BFM 86/90, all Non-HR patients received extended T.I.T (×18) as CNS preventive treatment, and VP-16 was added systemically in between the HD-MTX (5g/m²). In INS 98, based on ALL-BFM 95, VP-16 was omitted and pulses of VCR+DEXA were added in maintenance. Patients with T-ALL Non-HR and WBC >100000, were assigned to receive CRT 12 Gy, following the results of the AIEOP-ALL 91 (Conter J.C.O. 15:2786–2790, 1997) reporting inferior outcome in this group when comparing T.I.T only to BFM with irradiation. T-ALL HR patients were treated without modification and were all assigned to CRT 18 or 12Gy.

Results: Between 1989 and 2002, 145 T-ALL children aged <18 years were enrolled in the INS 89 (84 patients, 1989–97) and INS 98 (61 patients, 1998–2002). With a median follow-up of 12 and 5 years in INS 89 and INS 98 respectively, the 5 year event-free-survival (EFS) was 61.9±5.3% and 75.4±5.5%, respectively (p=0.14), and CNS relapse (isolated and combined) rates were 4.1% and 1.8%, respectively (p=0.4). Overall 5 yrs EFS, DFS, and CNS relapse rate of all the T-ALL patients were 67.4%, 78.8%, and 3.1% respectively. Outcome of Non-HR patients with WBC <100000 (all were non irradiated 72 pts) was; EFS 74.7%, and no CNS relapse. In the Non-HR with WBC >100000 (without CNS involvement) 9 patients were irradiated and 18 patients received the Extended T.I.T. These groups had 5 yr EFS of 78%±14% and 76%±10% respectively, and CNS relapse rate 11.1% and 5.6% respectively (p=0.59). In the HR group (34 pts) the 8 patients who refused CRT fared significantly worse than the irradiated patients, with EFS of 38%±17% Vs 73%±11% (p=0.08), and CNS relapse rate of 17% Vs 0 (p=0.14). T-cell ALL Non-HR children (prednisone good responders), in the context of the ALL-BFM intensive protocols and extended T.I.T may not require preventive CRT regardless of their WBC at presentation.