Ray Pais

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.

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.

Natural killer cells in children with malignant solid tumors. Effect of recombinant interferon-α and interleukin-2 on natural killer cell function against tumor cell lines

Natural killer (NK) cells and NK cell activity were determined in three groups (newly diagnosed [n = 21], on therapy [n = 21], and off therapy [n = 18]) of children with various types of malignant solid tumors and in a control group (n = 26) by means of Leu‐7 and Leu‐11b monoclonal antibodies and a 4‐hour 51Cr‐release assay, respectively. The erythroleukemia cell line K562 was used as a target cell. The newly diagnosed group included eight patients with localized disease (Stage I‐II), ten with bulky but nonmetastatic disease (Stage III), and three with metastases (Stage IV). The mean percent of NK cell activity in the newly diagnosed group was significantly higher than that of the control group. Children with Stage III tumors at diagnosis had higher mean NK cell function than those with Stage I‐II and Stage IV. On therapy patients had significantly fewer NK cells and lower NK cell cytotoxicity than those in the other groups studied. We also studied the following: (1) the in vitro effect of recombinant interferon‐α (rIFN‐α) and recombinant interleukin‐2 (rIL‐2) on NK cell function of peripheral blood lymphocytes (PBL) from children with solid malignancies; and (2) the susceptibility of neuroblastoma‐derived (CHP‐126 and SKNSH) and rhabdomyosarcoma‐derived (A‐204) cell lines to NK cell lysis. Both rIFN‐α and rIL‐2 enhanced NK cell activity of PBL from children with malignancies and healthy children against K562 and solid tumor cell lines. The enhancing effect or rIL.‐2 was greater than that of rIFN‐α. CHP‐126 and SKNSH cell lines were susceptible to NK cell lysis mediated by the PBL of children with neuroblastoma and the control group. The A‐204 cell line was less sensitive than K562 to NK cell cytotoxicity. Our results suggest a potential therapeutic role for both cytokines in the treatment of malignant solid tumors of childhood.

Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study.

Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.

Abnormal vitamin B6 status in childhood leukemia.

Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5′‐phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age‐matched controls. the children with leukemia had significantly lower PLP levels than the controls. in 26 additional leukemia patients and 26 additional controls, a high‐performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). the PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness‐related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status.

Non-Hodgkin's lymphoma presenting as a rectal polyp in a child

Primary lymphoma of the rectum is extremely rare in children. We report here a 10-year-old boy with localized non-Hodgkins lymphoma, discovered within a rectal polyp. The literature on childhood rectal lymphomas is reviewed. This case illustrates the importance of considering the possibility of malignancy with rectal polyps, even in children.