[Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study]. / Einfluss von Dosisintensität und therapiebedingter Leukozytopenie in der Intensivtherapie auf die Prognose bei akuter lymphatischer Leukämie im Kindesalter. Untersuchungen bei 213 Patienten der Studie COALL-85. COALL-Studiengruppe.

Dose intensity (DI) plays an important role in the treatment of neoplastic diseases. The individual DI within a protocol may vary considerably and thus may be an important prognostic factor. In 213/305 patients treated in the cooperative study COALL-85 for childhood acute lymphoblastic leukemia the following parameters of individual therapy intensity were analyzed: Total time for intensive treatment, cumulative doses of single drugs, mean relative dose (= relation between received and prescribed doses of all drugs), mean relative dose intensity ( = mean relative dose/time) as well as frequency and duration of leukocytopenia. Therapy for LR (low-risk) and HR (high-risk) patients were separately analyzed by both life-table method and multivariate regression analysis. Neither length of time, mean relative dose intensity nor the other parameters had any significant influence on prognosis within the HR protocol. The only significant prognostic factor was the remission status on day 28 (p less than 0.001 in multivariate analysis). In contrast patients treated with the LR protocol had significantly fewer relapses if treatment resulted in leukocytopenic episodes (probability for event free survival (EFS) = 0.76 in patients with one or two leukocytopenic episodes compared to 0.52 in patients with none). Patients with a mean relative dose greater than 0.9 showed a higher EFS of borderline significance than patients with mean relative dose less than = 0.9 (0.72 vs 0.49, p = 0.09). We would like to conclude, that treatment protocols with very intensive and prolonged combination chemotherapy have a certain margin of safety in DI without disadvantage for the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

[Initial response to therapy as an important prognostic factor in acute lymphoblastic leukemia in childhood. COALL study group]. / Initiales Ansprechen auf die Therapie als wichtigster prognostischer Faktor bei der akuten lymphoblastischen Leukämie im Kindesalter. COALL-Studiengruppe.

Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL-ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS)

[High-dosage intralumbar methotrexate administration. A report on clinical experience]. / Hochdosierte intralumbale Methotrexatgaben. Klinischer Erfahrungsbericht.

In therapy and prophylaxis of meningeal leucemia, more than 400 injections of methotrexate, in doses between 15 mg and 50 mg (sometimes up to 75 mg) have been administered to 71 children without severe neurotoxic sequelae. This high dosage was applied repeatedly from 1970 to 1980 in 45 children suffering from acute lymphoblastic leucemia as CNS prophylaxis during a course of cobalt 60 irradiation of the skull. Since then primary CNS relapses have not been observed in these patients. The astonishing fact that these high intrathecal doses of methotrexate have been tolerated without adverse side effects may be attributed to the long intervals of at least 7 days between the individual applications.

[Vaccination of children against influenza]. / Grippeschutzimpfung bei Kindern

In 19 children of 1-7 years of age hemagglutination inhibiting antibodies were measured before and after vaccination against influenza. Before vaccination the serum titers have been markedly lower than in adults. A single vaccination with Alorbat, a vaccine of representative strains of influenza virus inactivated and adsorbed to aluminumoxide, was followed by the same rise of titer as in adults. Therefore with this vaccine a single vaccination is effective in children, and a booster 4 weeks later, as recommended otherwise, is not necessary.