Women treated during childhood for HL with MOPP seem to have a distinctly lower ovarian reserve as measured by lower AMH values at early adulthood, compared with healthy women. Moreover, AMH seems to be the only predictor that is sufficiently sensitive to detect this decrease in ovarian reserve.

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can succesfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixtyseven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients Ͼ1 year of age at diagnosis unfavorable prognostic factors were male sex, Ͼ25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) Ͼ50 × 10 9 /l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.

BackgroundAlthough it is accepted that pediatric cancer treatment harbors a risk of gonadal damage, large cohort studies using up‐to‐date fertility markers are lacking.ProcedureThe aim of our study was to evaluate the gonadal toxicity of childhood cancer treatment using fertility markers. We included 248 adult male long‐term survivors of childhood cancer. Median age at diagnosis: 5 years, median age at follow‐up: 24 years, median follow‐up time 18 years. We evaluated patient characteristics, treatment modalities, testicular size, and endocrinological parameters including Inhibin B, luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and testosterone.ResultsThe median value of Inhibin B in the cancer survivor group was 126 ng/L versus 177 ng/L in the control group (P < 0.001). In the survivors, 67% had Inhibin B levels below the normal reference value of 150 ng/L compared with 26% in the control group (P < 0.05). Inhibin B was the most sensitive discriminator between survivors and controls. Significantly decreased Inhibin B levels and increased FSH levels were found in men treated for Hodgkin and non‐Hodgkin lymphoma, acute‐myeloid leukemia, neuroblastoma, and sarcoma as compared to other malignancies. Cumulative dosages of procarbazine and cyclophosphamide were the only independent chemotherapy‐related predictors for decrease of Inhibin B levels and increase of FSH. Age at time of treatment did not influence post‐treatment Inhibin B or FSH levels.ConclusionsSevere gonadal impairment is a risk in a considerable subgroup of childhood cancer survivors based on current fertility markers like Inhibin B. Males receiving gonadotoxic treatment before puberty are not protected from post treatment gonadal dysfunction. Pediatr Blood Cancer 2009;52:108–112. © 2008 Wiley‐Liss, Inc.