Abdel Ragab

Adolescent Cancer Survivors: Psychosocial and Familial Adaptation

Adolescent cancer survivors were compared with nondiseased control subjects on measures of adaptation, coping, body image, sexual adjustment, psychopathology, and family functioning. Cancer survivors reported no major difficulties in social competence, overall coping, and family communication. Although their school teachers reported no symptoms of psychopathology, the cancer survivors did report body image disturbances and adjustment difficulties. Further, the surviving adolescents were eager to present themselves favorably. Compared with nondiseased control families, families of survivors were characterized as somewhat inflexible. Implications for clinical practice include the careful monitoring of youth who have survived cancer as well as sensitivity to underlying concerns that the survivors and their families may avoid.

Chemotherapy for acute lymphocytic leukemia: Cognitive and academic sequelae

Iatrogenic cognitive impairments have been reported for survivors of childhood leukemia after prophylactic central nervous system therapy with craniospinal radiation. To determine whether chemotherapy alone might be a source of central nervous system damage, we assessed in a cross-sectional design the cognitive and academic functioning of 48 children with acute lymphocytic leukemia who were at various stages in their treatment or who had completed treatment. The off-therapy patients who had completed a 3-year course of chemotherapy were more impaired in tasks of higher-order cognitive functioning than were those children whose leukemia had been newly diagnosed and those children whose diagnoses had been 1 year earlier. Off-therapy patients also had concomitant diagnosable learning disabilities in mathematics. We recommend appropriate liaison and special education placements, as well as continued evaluation of cognitive and leaning functioning of children treated for moderate-risk acute lymphocytic leukemia who receive chemotherapy alone.

Sarcomas of the vagina and uterus: The intergroup rhabdomyosarcoma study

During a 12-year period (1972-1984), 43 patients with sarcomas of the female genital tract were admitted to the Intergroup Rhabdomyosarcoma Study (IRS), including 31 with primary tumors of the vagina; and 12 with tumors of the uterus, including the cervix. Thirty-four of these can be evaluated on the basis of periods of observation from 18 months to 12 years. Primary tumors of the uterus were a distinct group, distinguished from those arising in the vagina by patient age-range and probably by prognosis, as well as site. Patients with vaginal tumors, with a mean age of 1.8 years, responded to a multimodality approach employing combinations of chemotherapy (vincristine sulfate and actinomycin D, or the aforementioned two drugs with cyclophosphamide +/- doxorubicin hydrochloride), irradiation, and/or surgery, with only one tumor-related death, among 24 evaluable patients. In contrast, among the patients with primary uterine tumors, in which the mean age was greater than 14 years, four of ten evaluable patients died secondary to tumor relapse or progression.

Family Adaptation and Coping Among Siblings of Cancer Patients, their Brothers and Sisters and Nonclinical Controls

Abstract This study examined coping and family adaptation in siblings of cancer patients, their ill brothers or sisters, and a control group consisting of nonclinical children who have healthy siblings. Assessments included childrens self-report measures of coping and family adaptation. Variables of individual differences, including gender and age of the sibling, and family constellation factors, including birth order and number of siblings in the family, were examined to determine effects on coping. Better adaptation was found in larger families, while decreased family involvement was found among older siblings. Recommendations for future research include elucidating the process by which children adjust to having a chronically ill sibling in their family.

Mortality among children with rhabdomyosarcomas of the alveolar histologic subtype

Of 116 patients with rhabdomyosarcoma of the alveolar histologic subtype who entered the Intergroup Rhabdomyosarcoma Study (IRS) from 1972 to 1978, there were 72 deaths (63%), compared with a mortality of 39% among patients with all nonalveolar types combined. The subgroup with alveolar histology contributed greater than 29% of the total mortality, although it represented 20% of the total patients (p less than .001). This recurrence rate reflects increased local, regional, and distant relapse. Differences were most marked in patients with grossly excised tumors (clinical groups I and II) in which the mortality was 44% in patients with alveolar tumors (48 patients) versus 13.5% in those with embryonal histology (111 patients), and 16% in all patients with nonalveolar tumor types. When survival was influenced by primary tumor site this reflected, in most body areas, an increase in the proportion of patients with the alveolar histology in that site. Patients with unresected or disseminated tumors (clinical groups III and IV) of the alveolar subtype have initial response rates to VAC and radiotherapy which are similar to those of patients with tumors of other cell subtypes (70% for group III and 50% for group IV). In these clinical groups, the differences in survival related to histologic subtype are not significant. The presence of the alveolar histologic subtype represents a rational basis for employing more intensive therapy in the management of patients with rhabdomyosarcomas.

Cognitive Status of Children Treated with Central Nervous System Prophylactic Chemotherapy for Acute Lymphocytic Leukemia

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with craniospinal radiation. We examined the neurocognitive status of 46 children with acute lymphocytic leukemia (ALL) to assess the impact of a regimen consisting of systemic chemotherapy and prophylactic CNS chemotherapy. By comparing three groups of ALL children (i.e., patients whose diagnosis was recent, patients 1 year postdiagnosis currently receiving CNS prophylactic chemotherapy, and off-therapy patients who had been treated with chemotherapy for 3 years) and their healthy siblings on measures of sequential and simultaneous processing, we were able to examine the effects of CNS prophylactic and systemic chemotherapy at various points during treatment. Results indicate that the children who had received a 3-year course of chemotherapy (off-therapy patients) were more impaired on tasks involving right-hemisphere simultaneous processing than were sibling controls or ALL children whose diagnosis was recent and whose treatment had just begun. Age at diagnosis did not interact with the effects of chemotherapy. These findings support the need for continued evaluation of cognitive functioning in ALL, children receiving CNS prophylactic chemotherapy to identify potential harmful neurocognitive sequelae of treatment.

A phase II trial of continuous-infusion 6-mercaptopurine for childhood solid tumors.

SummaryA phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6-MP) in patients with refractory solid tumors or lymphoma was performed. The dosing schedule of 50 mg/m2 per hour for 48 h was chosen to produce optimal cytotoxic concentrations of 6-MP. There were no complete or partial responses in the 40 patients entered in the trial. Accrual was sufficient for the conclusion to be drawn that there was >95% probability that the true response rate was no greater than 22% and 26% in osteosarcoma and Ewing’s sarcoma, respectively. Dose-limiting toxicity was observed in one-third of the patients and included reversible hepatotoxicity, myelosuppression, and mucositis. The excellent penetration of drug into the cerebrospinal fluid (CSF) suggests that future trials of this intravenous dosing schedule should be conducted on tumors of the CNS.

Effects of folate in culture medium on common fragile sites in lymphocyte chromosomes from normal and leukemic children.

SummaryThe expression of common fragile sites at 69 bands was evaluated in 20 normal children and in 15 children with newly diagnosed acute leukemia using medium with folate (FA+) and without folate (FA-). As expected, the FA- medium significantly increased expression of aberrations in all study groups but the differences were larger for normal children than leukemic children. The major effect of the FA- medium was a generalized increase in aberration frequency over all sites rather than site-specific increases. A tendency toward clumping of aberrations within cells was exhibited in both media. Aberrations were seen at 81% (FA+) and 83% (FA-) of the 69 bands, with 4 sites -3p14, 6p21, 9q13, and 17q23 — recorded in most of the study individuals. In addition, 12 sites not previously recorded as common or rare sites had significant levels of expression in at least one study group.

Evaluation of AMSA in children with acute leukemia. A pediatric oncology group study

One hundred four children with advanced leukemia in relapse (74 with acute lymphocytic leukemia [ALL] and 30 with acute nonlymphocytic leukemia [ANLL]) received AMSA (4′‐(9‐Acridinylamino)methanesulfon‐m‐anisidide) at a dose of 120 mg/m2/day for 5 days (Regimen I) or 60 mg/m2/day for 10 days (Regimen II). Children with ALL were randomized between Regimens I and II (31 and 36 evaluable patients, respectively). All 29 evaluable patients with ANLL were treated on Regimen I. Eighty‐eight percent of evaluable patients experienced severe or life‐threatening toxicity, with no statistical differences between Regimens I and II. Bacterial or fungal infections (considered life‐threatening or fatal) occurred in 17 children with ALL and in 7 with ANLL. Fatal cardiac toxicity occurred in one patient. Complete or partial response occurred in 25.0% (SE = 8.8%), 28.1% (SE = 8.0%), and 25.9% (SE = 8.4%) of evaluable patients on ALL Regimen I, ALL Regimen II, and ANLL, respectively. However, responses were of short duration (16–91 days). There was no significant difference in the duration of survival from treatment start for the two ALL regimens (P = 0.46). The median duration of survival for ANLL patients was significantly longer (P = 0.004) than that of ALL patients treated on Regimens I and II combined. Eighty‐two percent of the complete or partial responses (18 of 22) occurred after the first course of AMSA. At the dose schedules investigated, and in a heavily pretreated patient population, AMSA had activity in childhood leukemia. However, the high incidence of severe, life‐threatening, or fatal infections meant that the quality and quantity of responses and survival was not commensurate with the toxicity, and that it would be difficult to incorporate this drug into combination chemotherapy with other myelosuppressive agents.

Characterization of a new chromosomal marker for acute lymphoblastic leukemia from a long-term cell line

A bone marrow aspirate from a child with acute lymphoblastic leukemia (ALL) at first relapse was used to establish cell line # 697. The cultured line and marrow aspirates taken at initial diagnosis and first relapse were examined and compared. Similarities in all patterns evaluated confirmed the leukemic origin of the line. Morphologically, the cells were typically lymphoblastic. Cytochemically, they were slightly acid phosphatase-positive and negative for peroxidase, ASD chloroacetate esterase, and nonspecific esterase. Immunologically, they were found positive for common-ALL antigen (CALLA), Ia-associated antigen, terminal deoxynucleotidyl transferase (TdT), and cytoplasmic IgM (cIgM) and slightly positive for surface IgM (sIgM). Testing for Epstein-Barr virus (EBV) capsid antigen was also positive. Cytogenetic evaluations performed on initial, relapse, and cell line specimens each revealed the presence of a pseudodiploid cell line characterized by a consistent marker chromosome. GTG-, QFQ-, and RF-banding identified the marker as being derived from a translocation involving chromosomes #7 and #19: t(7;19) (q11;q13). Iso 7q, -5, -9, and +2 were also found in significant association with the marker and were viewed as demonstrating continued karyotypic evolution within the cell line. From these data, cell line #697 has been classified as a leukemic line of B-cell lineage in a transitional stage between pre-B and mature B cells.