Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

One quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fanconi anemia, Bloom syndrome, ataxia teleangiectasia and some immune disorders, but these represent a very small minority of cases. In the last decades survival of childhood cancer improved significantly. Because of this, the side effects of treatment, both during and after therapy become increasingly important. The 5-year survival rates of acute Lymphoblastic leukemia (ALL) increased to 80% in the last years. Since the mid-seventies, in the Netherlands children with ALL are treated uniformly, according to national protocols of the Dutch Childhood Oncology Group (DCOG). Early protocols were prednisolone based and used cranial radiotherapy (CRT) as central nervous system (CNS) prophylaxis. The dexamethasone based DCOG ALL-6 protocol in the mid-eighties was the first protocol that did not use CRT as CNS prophylaxis. The ALL-7 and ALL-8 protocols were prednisolone-based protocols, similar to the BFM-protocols used in Germany. In this thesis most children were treated according to the DCOG ALL-9 protocol, based on the previous, dexamethasone based, ALL-6 protocol, which consisted of an induction, CNS prophylaxis, consolidation (high risk only) and maintenance phase, for a total of 109 weeks. Patients with peripheral white blood cell counts over 50 x 109/l, T-cell phenotype and/or mediastinal mass, extramedullary leukemia, patients with t(9;22), 11q23 with MLL gene rearrangements and non-responders to induction chemotherapy, were stratified to a high risk (HR) treatment schedule. Patients in the HR group received an intensive consolidation phase after induction. CNS prophylaxis consisted of recurrent intrathecal triple therapy with prednisolone, methotrexate (MTX) and cytarabine (Ara-C) combined with post remission MTX. Total cumulative doses of the chemotherapeutic agents used in the high risk and non-high risk (NHR) protocol are shown in table 1.

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