thioguanine-anhydrous and Neurofibromatosis-1

A 9-month-old boy with known familial neurofibromatosis type I (NF-1) presented with a clinical and laboratory picture suggestive of juvenile chronic myelomonocytic leukemia (JCMMoL). Chromosomal studies obtained from the bone marrow indicated, however, that he had monosomy 7 syndrome. We believe this is the first reported case of monosomy 7 syndrome in a child with NF in the United States, and that this case complements a recent report of two cases of NF, JCMMoL, and monosomy 7 in Japanese children. Since monosomy 7 syndrome is very difficult to differentiate from JCMMoL or acute nonlymphocytic leukemia (ANLL) unless appropriate chromosomal studies are obtained, we believe it is possible that monosomy 7 may occur with increased frequency in patients with NF-1. Monosomy 7 syndrome might therefore be a significant cause of the known association between NF-1 and nonlymphoid leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Chromosomes, Human, Pair 7; Combined Modality Therapy; Cytarabine; Daunorubicin; Dexamethasone; Diagnosis, Differential; Etoposide; Humans; Infant; Leukemia, Myelomonocytic, Chronic; Male; Monocytes; Monosomy; Neurofibromatosis 1; Pedigree; Preleukemia; Syndrome; Thioguanine

To evaluate tumor responses, event-free survival (EFS), overall survival (OS), and toxicity of chemotherapy, children with neurofibromatosis type 1 (NF1) and progressive low-grade glioma were enrolled into the Children's Oncology Group (COG) A9952 protocol and treated with carboplatin and vincristine (CV).. Non-NF1 patients were randomized to CV or thioguanine, procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine in COG A9952. NF1 patients were assigned to CV only. NF1 patients and non-NF1 patients who were treated with CV were compared with respect to baseline characteristics, toxicity, tumor responses, EFS, and OS.. A total of 127 eligible patients with NF1 were nonrandomly assigned to CV: 42 NF1 patients (33%) had events, and 6 (4.7%) died. The 5-year EFS rate was 69% ± 4% for the CV-NF1 group and 39% ± 4% for the CV-non-NF1 group (P < .001). In a univariate analysis, NF1 children had a significantly higher tumor response rate and superior EFS and OS in comparison with CV-treated children without NF1. NF1 patients and non-NF1 patients differed significantly in amount of residual tumor, extent of resection, tumor location, and pathology. According to a multivariate analysis, NF1 was independently associated with better EFS (P < .001) but not with OS. NF1 patients also had a decreased risk of grade 3 or 4 toxicities in comparison with non-NF1 patients. Three second malignant neoplasms occurred in NF1 patients receiving CV (CV-NF1 group) at a median of 7.8 years (range, 7.3-9.4 years) after enrollment, but there were none in the non-NF1 group.. Children with NF1 tolerated CV well and had tumor response rates and EFS that were superior to those for children without NF1. Cancer 2016;122:1928-36. © 2016 American Cancer Society.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Child; Child, Preschool; Female; Glioma; Humans; Male; Neurofibromatosis 1; Procarbazine; Thioguanine; Vincristine

The optimal management of optic pathway gliomas (OPGs) is complicated by their variable natural history, the association with neurofibromatosis type 1 (NF1) and difficulties in defining progression and response to treatment.. This study is a retrospective review of all children presenting to a single institution with an OPG between 1990 and 2004.. Of the 133 children included, 78 (59%) had NF1; 87 (71 NF1) were observed initially, of whom 23 (11 NF1) subsequently required treatment. Forty-six patients received immediate treatment. Initial treatment, without or with an observation period, comprised chemotherapy alone (32, 11 NF1); debulking + chemotherapy (15, 4 NF1); gross total resection (6); radiotherapy (2); debulking + radiotherapy (3); and debulking only (12, 3 NF1). Overall, 16 patients were irradiated during the study period. Four children died (overall survival at 5 and 10 years was 97.6% and 94.6% for those who required treatment). Progression-free survival (PFS) for the 69 patients who needed treatment was 48%. There was no difference in PFS between chemotherapy versus chemotherapy + debulking or debulking alone. PFS for the NF1 patients who required treatment was similar to that of non-NF1 patients. Mean follow-up time was 9.0 (range 0.6-18.0, median 8.6) years.. The study confirms the complexity of OPGs and that NF1 is a major determinant of the resultant behavior of the tumor.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Brain Damage, Chronic; Carboplatin; Child; Child, Preschool; Combined Modality Therapy; Cranial Irradiation; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Infant; Intellectual Disability; Lomustine; Male; Neurofibromatosis 1; Optic Nerve Glioma; Procarbazine; Retrospective Studies; Survival Analysis; Thioguanine; Treatment Outcome; Vinblastine; Vincristine; Vision Disorders

A patient with nonfamilial peripheral neurofibromatosis (NF) (von Recklinghausen's disease) is reported who contracted acute monocytic leukemia at 60 years of age. In the course of the illness, myelonecrosis developed and the patient died 4 months later due to a therapy-resistant bone marrow relapse. This association of the two illnesses would appear to confirm reports on an increased incidence of nonlymphatic leukemia and NF. Such an association is seen during childhood as juvenile chronic leukemia, but it is uncommon in adulthood.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blotting, Southern; Cytarabine; Daunorubicin; Humans; Leukemia, Monocytic, Acute; Male; Middle Aged; Neoplasms, Multiple Primary; Neurofibromatosis 1; Thioguanine