Jordan R. Wilbur

Disseminated necrotizing leukoencephalopathy: A complication of treated central nervous system leukemia and lymphoma

This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitts lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuro‐pathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swellings both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.

Adriamycin Activating a Recall Phenomenon After Radiation Therapy

Excerpt To the editor: Adriamycin has antineoplastic activity in malignant lymphomas, bone and soft tissue sarcomas, neuroblastomas, and some carcinomas (1). Toxicity reported includes leukopenia, ...

Non‐Hodgkin's lymphomas. VI. Results of treatment in childhood

A retrospective study was undertaken reviewing records of all children seen in the Division of Radiation Therapy at Stanford University Hospital between 1961 and 1971 with a diagnosis of non‐Hodgkins lymphoma. Of 41 patients who had been originally diagnosed as having a non‐Hodgkins lymphoma, a diagnosis was confirmed in only 32. Two cases were interpreted as malignant histiocytosis, and 7 other patients were diagnosed as having Hodgkins disease. Of the 32 patients with a non‐Hodgkins lymphoma, all but 1 had lymphoma of the diffuse type, with diffuse histiocytic lymphoma being the most common histologic diagnosis. Lymphangiography was attempted in all but 1 patient. Fifty‐five percent of Stage I patients and 38% of Stage II patients are alive and free of disease more than 2 years after the completion of radiation therapy alone. There were no relapses seen after 12 months. Bone marrow involvement was seen in 5 patients at presentation and developed in an additional 8 patients following the initiation of radiation therapy.

Guidelines for a therapeutic alliance between families and staff: A report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the childs best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

Chemotherapy of sarcomas

The development of intensive treatment techniques with combination chemotherapy, radiation, and selected surgery has produced dramatic improvements in the treatment of soft tissue sarcomas. This has been best demonstrated in the long‐term disease‐free survival of a majority of children with inoperable or metastatic embryonal rhabdomyosarcoma treated with VAC chemotherapy (vincristine, actinomycin D, and cyclophosphamide). The addition of adriamycin and imidazole carboxamide to the combination therapy program for adults with soft tissue sarcomas has resulted in significant improvements in their response rates as well.

Interferon production in human mumps infections.

Summary The production and variation in titer of interferon during clinical mumps infection was studied in 45 subjects. Serum titers in the clinical disease were highest at 1-3 days and then fell, but on occasion persisted as long as the eighth day of illness. The saliva also contained interferon in concentrations roughly parallel to those in sera taken at the same time. The titers could not be correlated with severity of illnes or observed clinical course.

Leukoencephalopathy Following Combines Therapy of Central Nervous System Leukemia and Lymphoma

We report a form of disseminated necrotizing leukoencephalopathy observ. d. in five children with acute lymphoblastic leukemia or lymphoma, who receiv. d. systemic chemotherapy, brain radiation, and intrathecal (IT) methotrexate, cytosine arabinoside and hydrocortisone because of meningeal tumor involvement. Three children developed a progressive neurologic disease at the end of IT therapy or shortly thereafter. The lesions consisted in discrete, apparently coalescent foci of coagulative necrosis in the white matter, with a remarkable absence of inflammatory cells, little or no tissue breakdown, and striking axonal swellings. The adjacent tissue showed status spongiosus and moderate astrocytic hypertrophy. Vascular lesions were few and inconstant.

Rehabilitation of children with cancer

The majority of children with cancer can now be successfully treated with eradication of their disease if they receive the best therapy available in experienced cancer treatment centers. This has become possible due to five major factors: 1) the availability of new antitumor drugs, 2) the utilization of new therapeutic techniques, 3) improved supportive therapy, 4) the development of the cooperative, coordinated team approach, and 5) the philosophy of the therapeutic approach. With this increasing success, the long‐term physical and emotional rehabilitation of the child with cancer becomes of great importance. The goal is a return of the child and his family to as normal a lifestyle as possible as quickly as possible. The achievement of this involves an aggressive and positive approach to the overall treatment plan, with involvement of all of the members of the treatment‐rehabilitation team, including the patient and his family.

Successful treatment of inoperable embryonal rhabdomyosarcoma

Embryonal rhabdomyosarcoma, when inoperable or metastatic, has usually ben a rapidly fatal cancer. Intensive combination chemotherapy (VAC) with Vincristine (VCR), Actinomycin-D (AMD) and Cyclophosphamide (CYT) in conjunction with radiotherapy is effective in the treatement of this tumor. Twenty-one children with inoperable or metastatic embryonal rhabdomyosarcoma, or undifferentiated sarcoma suggestive of embryonal rhabdomyosarcoma, were treated in the 3-year period 1967–1969. Sixteen of them (76%) are alive without evidence of disease 1–4 years after initiation of therapy. Therapy consisted of biopsy, Co80 radiation 5000–6000 rads tumor dose, and VAC chemotherapy. Surgery was subsequent;ly utilized when feasible. The chemotherapy consisted of VCR 2 mg./M2 IV weekly x12, AMD 75 MG./kG. divided into 5–8 daily doses every 3 months for 5 or 6 courses, and CYT given either as 2.5 mg./Kg./day for 2 years or 10 mg./Kg./day for 7 days every 6 weeks. The type of CYT therapy was dependent on tumour location and extent.

Endomyocardial biopsy to monitor anthracycline therapy in children.

Evaluation of the ultrastructure of material obtained by endomyocardial biopsy has been proposed as a means to evaluate patients for impending anthracycline cardiotoxicity. Eighteen biopsies obtained from 13 patients (age, 3-18 years) are reported. Twelve biopsy procedures were done to evaluate the cardiac status on reaching a cumulative dose of 400 mg/m2 and three patients had six subsequent biopsies after having received significantly more drug or receiving radiation therapy to the lungs or mediastinum. Scores were assigned to the tissue obtained and used to guide the decision to continue or stop anthracycline therapy. Three patients with abnormal cardiac studies at low cumulative doses, five of whom had received greater than 400 mg/m2 and three of whom had received considerably higher doses and thoracic irradiation were given more drug without incident. Two specimens were interpreted to indicate avoidance of further anthracycline and two patients were cautiously given more despite evidence of mild myocardial damage. These results indicate that endomyocardial biopsies can be performed on a pediatric population with a reasonable complication rate. Further studies should be undertaken to evaluate its usefulness as a means to predict and avoid anthracycline cardiomyopathy.