Nomie A. Shore

A fatal X-linked recessive reticuloendothelial syndrome with hyperglobulinemia: X-linked recessive reticuloendotheliosis

In the past two generations of a Latin American family, 17 preschool-age boys died following a brief illness characterized by fever, hepatosplenomegaly, lymph node enlargement, purpura, hyperglobulinemia, and anemia. All were related through their mothers, and the disorder occurred in the pattern of an X-linked recessive trait. Postmortem examination of 12 boys revealed widespread infiltration by immature mononuclear cells and mature plasma cells. Results of extensive studies in the most recently affected boy are described.

ADRIAMYCIN CONTINUOUS I.V. INFUSION-HYPERFRACTIONATED RADIATION THERAPY FOR THE TREATMENT OF RECURRENT PEDIATRIC SOLID TUMORS

The prognosis of most pediatric solid tumors is poor upon development of recurrent disease. The study was designed to test the efficacy of Adriamycin (ADR) I.V. continuous infusion (CI) given simultaneously with hyperfractionated (HFT) radiation therapy (XRT) to such patients. The rationale for the study was: 1. ADR enhances XRT lethality of human cancer cells In vitro by inhibiting XRT repair process. 2. Small doses of XRT when given more than once daily may prevent tumor repopulation to a greater extent than higher doses given once daily. The study consists of ADR I.V. CI 12mg/m2/day x5 days and XRT tumor dose 100 rads twice a day at 6 hours intervals x5 days. Courses were repeated at 3-4 weeks intervals. Three children have been treated; 1 Ewings sarcoma (ES), 1 fibrosarcoma and 1 hemangiopericytoma, all have previously received ADR 480, 60 and 460mg/m2 respectively. The patient with ES has also received 5400 rads to the primary tumor. All 3 patients achieved partial remission after 2 courses of ADR I.V. CI-HFT-XRT and complete surgical excision of primary tumor was performed in the patient with ES after the 3rd course. Two patients developed progressive disease outside the XRT field 3 and 6 months post-therapy. The 3rd patients tumor is still under control while receiving the 3rd dose of therapy. This preliminary data suggests that the simultaneous administration of ADR I.V. CI-HFT-XRT can be an effective therapy for recurrent pediatric malignancies and should be tested in a larger number of patients.

An X-linked Recessive |[lsquo]|Malignant|[rsquo]| Reticuloendothelosis

In the last 2 generations of a Latin American family 17 males have died prior to 6 years of age. All were related in the family through their mothers. clinical information on 16 of the boys indicated that the illness was characterized by fever, pallor, jaundice, hepatosplenomegaly, and lymphadenopathy with the median age of onset of illness being 14 months (4–62 months) and the median duration of illness being 22 days (1–50 days). Histologic studies on 12 of the children revealed bone marrow plasmacytosis and a mononuclear cell infiltrate of the liver, spleen, and lymph nodes, and less frequently of the brain, kidney, heart, and lungs, consistent with a malignant reticuloendotheliosis.The most recently affected child was found to have anemia, thrombocytopenia, elevated IgG, IgA and IgM, normal phytohemagglutinin stimulation, in vitro transformation of peripheral blood lymphocytes, and an abnormal karyotype.All first-degree relatives of affected children have normal peripheral blood counts, karyotyping, delayed hypersensitivity and lymphocyte proliferation studies, normal to elevated IgG and IgM levels with normal IgA, and absence of in vitro transformation of peripheral blood lymphocytes.This is the first reported instance of a familial maliganant reticuloendotheliosis occurring in a pattern consistent with an X-linked recessive mode of inheritance.