Results of treatment with an intensive combination induction regimen containing idarubicin in children with acute myeloblastic leukemia: preliminary report of the Argentine Group for Treatment of Acute Leukemia.

In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and etoposide on days 6 to 8. A multidrug consolidation phase was subsequently administered and, after a treatment-free interval of 2 to 4 weeks, two 5-day intensification courses with high-dose cytarabine and etoposide were delivered with a 4-week interval between each course. Continuation therapy was started 2 to 4 weeks after the second course, with 6-thioguanine daily and cytarabine daily for 4 days every 4 weeks. Treatment was stopped after 18 months in children in continuous complete remission. A preliminary evaluation of this ongoing study included 36 patients with a mean age of 7.5 years (age range, 5 months to 16 years). The majority of patients had a French-American-British classification of M2 (n = 13) or M4 (n = 8). Complete remission was achieved by 91.7% of patients, while one died from sepsis in bone marrow hypoplasia and two were regarded as treatment failures. At a median follow-up of 12 months (range, 2 to 23 months) there were 12 adverse events: six bone marrow relapses, one bone marrow/skin relapse, and five deaths in complete remission (all deaths occurred during the consolidation phase). During the induction phase most of the patients experienced prolonged myelosuppression, and grade 3 to 4 toxicity (according to the Children's Cancer Group criteria) was frequently seen. Alopecia was universal. However, toxicity was manageable. We conclude that idarubicin in combination with cytarabine and etoposide is a highly effective regimen for induction in children with acute myeloblastic leukemia.

Gonadal effects of cancer therapy in boys.

A retrospective study of testicular histology was carried out in 21 prepubertal boys and in 11 intrapubertal or postpubertal boys who died from 1 day to 1 year after treatment with chemotherapy (CT) with or without radiation therapy (RT) for extragonadal solid tumors. Based on autopsy findings, profound histologic changes were found in six prepubertal boys and in all but one of the intrapubertal and postpubertal boys. For three of the prepubertal and five of the postpubertal boys with altered testicular histology, the contribution of pelvic RT could not be excluded. When prepubertal patients were evaluated according to nutritional status, a thickened tubular wall and absent or severely reduced spermatogonia were found in only 1 of 11 adequately nourished boys as compared with 5 of 10 malnourished boys. In intrapubertal and postpubertal boys, the tubular wall was thickened in six and these changes were independent of nutritional status. All malnourished intrapubertal and postpubertal patients demonstrated impaired spermatogenesis (versus 67% of age-matched malnourished controls), whereas similar impairment was noted in 60% with adequate nutrition versus 20% of controls. The diffuse damage of germ cells and tubules in malnourished younger boys suggests that the prepubertal male is not necessarily protected against the reproductive effects of cancer therapy.

Gonadal effects of cancer therapy in girls.

The gonadal histology of 21 prepubertal, intrapubertal, and postpubertal girls who died 1 day to 2 months after cessation of therapy for extragonadal solid tumors was reviewed. In addition to focal or diffuse cortical fibrosis, a reduction in follicle numbers and impaired follicular maturation were observed in cancer patients independent of their pubertal age. These changes appeared to be more severe in malnourished patients and in girls who received multiple agent chemotherapy, with or without irradiation. Both before and after the age of 10 years, most cancer patients had a total number of follicles similar to that of age- and nutrition-matched controls. However, the majority of these girls displayed impaired follicular maturation as demonstrated by reduced numbers of growing and antral follicles compared to controls. Histologic evidence of ovarian damage suggests that the future reproductive performance may be impaired in some female cancer patients treated even before puberty.

Histiocytosis X in children: patterns of disease and results of treatment.

The pathologic materials and clinical courses of 36 children aged 1 month-22 years, with histiocytosis X (H-X) seen at the Philadelphia Children's Cancer Research Center from 1970 to 1979 were reviewed. The pathologic subtype of H-X was favorable (type II) in 31 patients, unfavorable (type I) in one patient, and unclassified in four patients whose specimens were limited to a skin biopsy. Sixteen patients had localized H-X involving bone (14 patients), soft tissue (1 patient), or skin only (1 patient); all are alive and well after treatment with surgery alone (12 patients), radiation therapy (RT) (3 patients), or observation (1 patient); only 1 of the 16 developed recurrent H-X. The other 20 patients presented with multifocal H-X involving the skeleton alone (3 patients); the skeleton and soft tissues other than liver (7 patients); soft tissue exclusive of the liver (3 patients); soft tissue including the liver (4 patients); or soft tissues, skeleton, and liver (3 patients). These 20 patients were treated with surgery alone (1 patient), RT (4 patients), or multiple drugs +/- RT (15 patients). Seven of the 20 patients are alive and well without recurrence at a median of 4 years after diagnosis. Nine of the 20 patients, including 3 with liver dysfunction, responded completely to initial therapy but developed recurrence; each was retreated with drugs and is alive and well at a median of 4 years. The remaining 4 patients had widespread disease with dysfunction of the liver and/or hematopoietic system at diagnosis, failed to respond, and died. We conclude that (1) patients with multiple bony lesions with or without associated soft tissue disease or skin involvement have a favorable outlook and do not require systemic chemotherapy; (2) systemic treatment also is unnecessary for patients with localized H-X since recurrence is rare; (3) drugs can benefit patients with multifocal H-X, although the optimal duration of therapy is unclear; and (4) favorable response to treatment indicates high probability of disease-free survival. However, organ dysfunction at diagnosis is ominous: four of seven patients with liver dysfunction are dead, as are all three patients who presented with peripheral blood count depression.