Intellectual function in long-term survivors of childhood acute lymphoblastic leukemia: protective effect of pre-irradiation methotrexate? A Childrens Cancer Study Group study.

Having demonstrated in a laboratory model that the neurotoxicity of CNS irradiation can be ameliorated with pre-irradiation methotrexate, we retrospectively compared two methods of CNS prophylaxis in childhood acute lymphoblastic leukemia which differed only in the timing of intrathecal methotrexate and radiotherapy. The results of standard IQ tests conducted 2-11 years after 24 Gy of cranial radiotherapy were obtained in 72 patients, of whom 27 had pre-irradiation methotrexate and 45 did not (control group). The two groups were otherwise comparable. In girls, the full-, performance-, and verbal-scale IQ scores were consistently higher in the pre-irradiation methotrexate group than in the corresponding control group (P less than 0.025). Among girls less than 5 years of age when irradiated, the mean IQ scores were 25-29 points higher after pre-irradiation methotrexate than after the control treatment (P less than 0.0007). These results suggest that pre-irradiation methotrexate may help prevent CNS radiotoxicity in children, and that the benefit is dependent on patient age and gender.

Pretreatment liver biopsy in 20 children with histiocytosis X: a clinicopathologic correlation.

Liver biopsies were done on 20 patients with histiocytosis X (HX) as part of pretreatment evaluation prior to entry on two Childrens Cancer Study Group protocols. Seventeen patients had hepatomegaly, and seven had one or more abnormal laboratory parameters using Lahey's criteria for liver dysfunction. Nineteen of 20 specimens showed various abnormalities of the portal triads. A single biopsy revealed normal liver. Among the changes were triaditis, bile duct proliferation, variable fibrosis with histiocytic infiltrates, and cirrhosis. One patient had typical granulomas of HX within the liver parenchyma in addition to portal triaditis. Patients with larger livers and dysfunction tended to show more marked histologic abnormalities in the portal triads. However, correlations among liver size, function, and pathology showed considerable overlap. Early death among these patients was more likely to be associated with progressive HX in other sites and/or infection. Death from cirrhosis and liver failure per se occurred in one patient 4 years after initial biopsy, but five other children had evidence of cirrhosis on biopsy or at autopsy. The majority of patients with triaditis initially did not have clinical evidence of progressive liver disease although four expired with other manifestations of HX or infection. Conversely, patients showing fibrohistiocytic changes or cirrhosis initially were likely to have continuing or progressive liver disease. Although the liver histology was not diagnostic of HX, the types of portal changes usually predicted the subsequent course of liver disease.

Pediatric orofacial and laryngopharyngeal rhabdomyosarcoma. An Intergroup Rhabdomyosarcoma Study report.

Eighty-nine children with localized rhabdomyosarcoma of orofacial and laryngopharyngeal sites were treated in accordance with the first and second Intergroup Rhabdomyosarcoma Study (IRS) protocols (IRS-I and IRS-II) between 1972 and 1984. Treatment included surgery (or biopsy) and chemotherapy for all patients and radiotherapy in the majority. The actuarial estimate of the three-year survival rate for all patients was 83% and did not differ significantly by primary site, histologic findings, or presence of adenopathy. A trend for a worse survival rate was seen in clinical group III patients and in those less than 5 years of age at diagnosis. Factors associated with an increased risk of local/regional relapse included omission of radiotherapy and a radiation dose of less than 40 Gy (4000 rad). We conclude that treatment of these patients as recommended in the IRS-I and IRS-II protocols results in very good local and regional tumor control and survival rates. Salvage therapy for local/regional recurrence may yield long-term remission and possibly cure.

Imaging of rhabdomyosarcomas of the head and neck.

Rhabdomyosarcoma (RMS) is the most common childhood malignancy of the head and neck. The Intergroup Rhabdomyosarcoma Study now divides head and neck RMS into three categories by site of origin: orbital, parameningeal (middle ear, paranasal sinuses, and nasopharynx), and all other head and neck sites. CT is clinically applicable in the diagnosis of RMS of the head and neck, in treatment planning, and in the follow-up of patients with these tumors. Specific areas of applicability include determination of the presence/absence of intracranial and meningeal involvement, definition of tumor extent to guide radiation therapy planning, and demonstration of tumor regression or recurrence during and after treatment. CT has played an important role in the dramatically improved prognosis seen in RMS over the last 10 years. The role of MR in evaluating these patients is not yet defined, but it has promise because of the ease of obtaining multiple projections and the avoidance of ionizing radiation.

Outcome of pregnancy in survivors of Wilms' tumor.

Outcome of pregnancy was reported by 99 patients who were cured of childhood Wilms' tumor at seven pediatric cancer centers during 1931 to 1979. These patients carried or sired 191 singleton pregnancies of at least 20 weeks in duration. Among the 114 pregnancies in women who had received abdominal radiotherapy for Wilms' tumor, an adverse outcome occurred in 34 (30%). There were 17 perinatal deaths (five in premature low-birth-weight infants) and 17 other low-birth-weight infants. Compared with white women in the United States, the irradiated women had an increased perinatal mortality rate (relative risk, 7.9) and an excess of low-birth-weight infants (relative risk, 4.0). In contrast, an adverse outcome was found in two (3%) of the 77 pregnancies in nonirradiated female patients with Wilms' tumor and wives of male patients. The high risk of adverse pregnancy outcome should be considered in the counseling and prenatal care of women who have received abdominal radiotherapy for Wilms' tumor.

Pulmonary blastoma associated with cystic lesions in children.

A 4-year-old boy had a pulmonary blastoma removed from the site of a persistent pulmonary cystic lesion present since 6 weeks of age. Bone metastasis appeared 4 months after diagnosis. Following radiation therapy to the bone and after 15 months of VAC chemotherapy, he developed further metastases which showed little response to adriamycin or radiation therapy. He died 2 years and 2 months after the initial operation. A review of other pulmonary blastomas associated with cystic lesions in children is presented.

Two-dimensional gel electrophoresis of cell proteins in childhood leukemia, with silver staining: a preliminary report.

We have investigated the potential of two-dimensional electrophoresis for identifying differences in protein patterns between acute lymphocytic (ALL) and acute myelogenous leukemia (AML). We studied blood cells directly isolated from seven children with non-T, non-B ALL and five with AML. Solubilized proteins were electrophoresed with the ISO-DALT system and made visible by silver staining. More than 800 spots were routinely detected in individual gels. Patterns for multiple runs of the same sample were indistinguishable. Most of the prominent spots were present in gels from all 12 of the individuals studied. However, substantial variability in spot intensity was observed, even among patients in the same group. Five spots were consistently present in gels of all the AML patient, and either completely absent or substantially decreased in ALL gels. Three other spots were present in ALL but not AML gels. We conclude that this may be a useful tool for characterizing leukemic cells.

Histiocytosis X: clinical trial of chlorambucil: a report from Childrens Cancer Study Group.

A prospective study for histiocytosis X was designed to determine whether "good risk" patients, ie, those without evidence of dysfunction of liver, lung, or hemopoietic system, would respond to single agent therapy; in this case chlorambucil (CMB) used in a dose of 5 mgm/m2/day. If there was no response after an adequate trial period, treatment was initiated with four drugs using a combination of prednisone, vinblastine, cyclophosphamide and methotrexate. There were 26 evaluable patients, 57% of whom were less than two years of age at onset of therapy. There were three complete and four partial responses to CMB for a response rate of 26.9%. Sixteen patients received an adequate trial of four-drug therapy with three complete and two partial responses for a response rate of 33%. These responses were inferior to those previously reported for either single agents or combined therapy in histiocytosis X.

Actinomycotic bowel and ureteral obstruction in a patient with Hodgkin's disease.

This is a case report of a patient who presented with colonic and ureteral obstruction 4 yr following diagnosis and abdominal-pelvic radiation therapy of stage IIA Hodgkin's disease. Biopsy of a pelvic mass revealed actinomycosis.

BCG in the treatment of acute lymphocytic leukemia.

Children with acute lymphocytic leukemia, who were in remission after induction with prednisone and vincristine and consolidation with intravenous methotrexate, were randomized into three groups receiving (1) no further therapy, (2) BCG, and (3) chemotherapy with biweekly methotrexate and monthly prednisone and vincristine. Children continuing in remission after 8 mo on chemotherapy in group 3 were rerandomized into three similar groups, i.e., no therapy, BCG, and chemotherapy. In the primary randomization, the median duration of remission was identical in the groups receiving no therapy or BCG, (4 and 4.3 mo respectively), and both were significantly less than the median duration of remission on chemotherapy which had not been reached prior to secondary randomization at 8 mo. Results of secondary randomization were similar to those of primary randomization. As used in this study, BCG was ineffective in prolonging drug-induced remissions either early in remission or when the leukemic cell population might have been further reduced after 8 mo of maintenance chemotherapy.

The role of chemotherapy in the management of soft tissue sarcomas.

Prior to the use of chemotherapy, survival for rhabdomyosarcoma which had been completely resected was 50-60%. A controled study done by Children's Cancer Study Group showed the effectiveness of combined chemotherapy used as part of primary therapy in similar patients. Children who received actinomycin D (Act D) and vincristine (Vcr) for 1 year after surgery and radiotherapy had a lower metastatic rate than those who received none. This combination resulted in an 89% survival in patients with localized disease which was surgically resectable. Patients with microscopic residual disease had a 91% survival. With more aggressive use of combined chemotherapy, experience has accumulated demonstrating improved response and survival in both localized and gross residual disease. Combinations of Act D, Vcr, and cyclophosphamide can reduce initial tumor size, making large tumor masses more amenable to surgery and radiotherapy. Currently, an intergroup study is testing the response to four different drug combinations and the duration of therapy needed for various stages of the disease.