Therapy of acute lymphocytic leukemia in childhood with intermediate dose methotrexate and CNS irradiation

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Abstract
One hundred and eight children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved in 94% of the cases with vincristine, L-asparaginase, adriamycine and prednisone. One hundred and one patients received three intermediate dose methotrexate (MTX) infusions combined with intrathecal MTX, followed by L-asparaginase 24 h later. High risk (HR) patients (n=50) were treated in addition with high dose cyclophosphamide and Ara-C over 3 weeks. One hundred and one patients received cranial irradiation (1,800 rads standard risk (SR)-patients, 2,400 rads HR-patients) and intrathecal MTX. Maintenance therapy was performed with the usual two drug combination of daily 6 mercaptopurine (6 MP) and weekly MTX orally. Based on phenotyping 67% of patients had common type ALL, and pre-T or T-cell type in 18%. Six per cent of the patients had leukemic blasts expressing both common ALL and T-cell markers (c/T-type); 9% had acute undifferentiated leukemia (AUL). Out of 108, 101 achieved a complete remission, 6 patients died during induction therapy, 1 was a non-responder and 9 patients relapsed. Of these 6 had haematological relapses, 2 had CNS relapse and 1 had a testicular relapse. Four patients died in continuous complete remission (CCR). For 101 patients the 30 months probability of CCR is 0.85 (± 0.05). For 51 patients with standard risk CCR probability is 0.98 (± 0.03), for 50 patients with high risk indices it is 0.65 (±0.11). Patients with c-ALL have a CCR survival of 0.85 (±0.07), those with T- or pre-T-ALL 0.88 (±0.09), all 5 patients with c/T-ALL alive in CCR. In our study pediatric AUL patients have the most unfavourable prognosis.