Ovarian function in female survivors after multimodal Ewing sarcoma therapy.

BACKGROUND: With advances in cancer care, more young women with Ewing sarcoma (ES) survive after treatment. Thus, we sought to analyze the ovarian function in prepubertal, pubertal and postpubertal females and young women receiving multimodal therapy for ES, and to identify patients at risk of infertility on whom fertility preservation would be indicated. PROCEDURES: Twenty-seven female survivors of ES were included in this retrospective multiinstitutional study. Patients were classified into four groups according to the treatment received: chemotherapy (CHT) without pelvic radiation (pRT), chemotherapy and pRT, CHT and autologous hematopoietic cell stem rescue (aHSCT) without pRT, and CHT + pRT + aHSCT. The ovarian function and fertility outcomes were analyzed. RESULTS: At a median follow-up of 5.7 years from diagnosis, and at median age at follow-up of 16.3 years, 67% of the survivors had premature ovarian insufficiency, including all patients receiving pelvic RT and 87.5% of patients who underwent aHSCT, independent of chemoprotection. Thirty-seven percent of patients had a clinical syndrome of premature menopause. The relative risk (RR) of premature ovarian insufficiency of a survivor was 3.9 (p 0.03) for pRT, and 2.4 (p 0.07) for aHSCT. On multivariate analysis, radiation therapy was a significant predictor of higher risk of premature ovarian insufficiency over chemotherapy alone. CONCLUSIONS: A large proportion of women receiving multimodal therapy for ES develop premature ovarian insufficiency. Patients and guardians should be informed about the reproductive potential and strategies for preservation of ovarian function should be considered individually. Pediatr Blood Cancer 2015;62:341-345. © 2014 Wiley Periodicals, Inc.

Thiopurine S-methyltransferase (TPMT) polymorphisms in children with acute lymphoblastic leukemia, and the need for reduction or cessation of 6-mercaptopurine doses during maintenance therapy: the Polish multicenter analysis.

BACKGROUND: 6-Mercaptopurine (6-MP) is used for the treatment of pediatric acute lymphoblastic leukemia (ALL). Mutations in the TPMT gene may influence the efficacy and safety of 6-MP treatment. This multicenter study investigated the association between TPMT genotype, 6-MP dose adjustments, and the incidence of adverse effects in patients. PROCEDURE: A total of 203 ALL children were genotyped using PCR/allele-specific amplification and PCR/RFLP. The control group consisted of 394 healthy volunteers. RESULTS: The TPMT*3A variant allele was found in 16 patients (15 TPMT*1/*3A, 1 TPMT*3A/*3A) and the TPMT*3C (A719G) allele in 1 patient. No TPMT*2 (G238C) or TPMT*3B (G460A) alleles were detected in the study group. TPMT*3A, TPMT*1 (wild-type), and TPMT*3C alleles were detected at frequencies of 3.94%, 95.81%, and 0.25%, respectively. The genotype and allele distributions were similar in the ALL and control groups. The 6-MP dose was reduced more frequently in patients with TPMT*3A and TPMT*3C alleles, compared with wild-type alleles (P = 0.042). Reductions because of leucopenia with respiratory tract infection, or because of leucopenia, anemia and/or thrombocytopenia were four (P = 0.007) and five (P = 0.03) times more common, respectively. The groups differed with regard to the rates of 6-MP dose reduction (P = 0.028). 6-MP was discontinued more often in patients with TPMT*3A and TPMT*3C alleles (14-fold) as a result of leucopenia, anemia, and/or thrombocytopenia (P = 0.004). CONCLUSIONS: The results indicate that TPMT genotype influences the safety and efficacy of ALL treatment and genotype information may therefore be useful for optimizing 6-MP therapy.

Amino acid profiles as potential biomarkers for pediatric cancers: a preliminary communication.

AIM: Childhood cancer remains one of the main cause of death in the pediatric population. Amino acids (AAs) level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease. METHODS: Seventy-seven children with cancer, including 47 with hematological and 30 with solid tumors were enrolled in this study and compared with healthy children. Twenty-two plasma-free AAs were determined by HPLC with fluorometric detection. RESULTS: The results revealed significant decrease in glutamine levels for oncological patients and significant increase in aspartic acid, glutamic acid, asparagine, serine, citrulline, alanine, GABA, tryptophan, methionine, valine, phenylalanine and isoleucine levels in cancer children versus control. CONCLUSION: Plasma-free AA profile as a biomarker, which combines metabolic and clinical data, as an innovative and interdisciplinary approach, may allow for faster detection of tumor occurrence, and in the future for monitoring patient during treatment, and possible prediction of cancer recurrence.