In vitro characteristics of childhood leukemic monoblasts.

Leukemic monoblasts obtained from three children were evaluated for their in vitro physiologic characteristics. These monoblasts were alpha naphthyl acetate esterase positive, exhibited glass adherence, had IgG membrane receptors, phagocytized latex particles with subsequent nitroblue tetrazolium (NBT) reduction, and matured to macrophages in vitro, either when adherent to glass slides or in feeder layer suspensions. Employing the double layer in vitro bone marrow culture technique, leukemic marrows from these children failed to produce colonies in culture in the presence or absence of normal feeder layers. Varying the concentration of leukemic cells in the feeder layers failed to augment colony growth from normal bone marrows. Although monoblasts were observed to mature to macrophages in vitro, no increase in colony stimulating factor activity was observed with aging of the feeder layers. These studies suggest that childhood leukemic monoblasts lack the ability to produce colony stimulating activity, differing in this respect from monoblastic leukemia in adults.

Effectiveness of enteral and parenteral nutrition in the nutritional management of children with Wilms' tumors.

The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutrition status and/or reversing protein-energy malnutrition was evaluated in nine children, ages 1 to 7 years (eight female), with Wilms' tumors. At the onset of treatment, eight patients received comprehensive enteral nutrition (CEN) which included intense nutritional counseling and oral supplements while one received total parenteral nutrition (TPN). Despite CEN, the initial, intense treatment period was associated with a decreased energy intake (64 +/- 27% Recommended Dietary Allowances), dramatic weight loss (22 +/- 7% by 26 +/- 17 days from the beginning of treatment), decreased skinfold thickness (< 10th percentile), and decreased albumin concentrations (< 3.2 g/dl). Four of those who initially received CEN subsequently required TPN. A total of five patients received TPN for a mean of 31 days (range 11 to 60); kcal averaged 105 +/- 9% Recommended Dietary Allowances during weight gain. At onset of TPN, the mean albumin, transferrin, total lymphocyte count were 3.02 +/- 0.45 g/dl, 155 +/- 40 mg/dl, and, 655 +/- 437/mm3, respectively; all children had abnormal anthropometric measurements and anergy to recall skin test antigens. TPN for 28 or more days supported weight gain (+ 2.44 kg), increased serum albumin (+ 0.58 +/- 0.47 g/dl) and transferrin (+ 76 +/- 34 mg/dl), and reversed anergy despite low total lymphocyte counts. During maintenance treatment, nutritional status was maintained or restored with CEN in the group who responded. These preliminary data document the severity of protein-energy malnutrition which accompanies initial, intense treatment of children with Wilms' tumors, the nutritional and immunological benefits of TPN during continuing intense treatment and the effectiveness of CEN in maintaining a satisfactory nutritional status during maintenance treatment.

Effectiveness of central parenteral nutrition versus peripheral parenteral nutrition plus enteral nutrition in reversing protein-energy malnutrition in children with advanced neuroblastoma and Wilms' tumor: a prospective randomized study.

The effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) plus enteral nutrition in reversing protein-energy malnutrition was evaluated in 19 children (nine CPN, 10 PPN) with advanced neuroblastoma or Wilms' tumor. Weekly dietary, anthropometric, and biochemical measurements were compared for 15 patients (eight CPN, seven PPN) who completed more than 25 days of nutrition support. The groups had similar mean energy and protein intakes (CPN: 95 +/- 5% of healthy children, 2.5 +/- 0.3 g/kg; PPN: 102 +/- 5% of healthy children, 2.9 +/- 0.3 g/kg). Increases in weight (p less than 0.001), subscapular skinfold thickness (p less than 0.001), albumin (p less than 0.05), and transferrin (p less than 0.05) for the first 28 days were significant and did not differ between groups. Fever, sepsis, elevated SGOT, and severe anemia occurred with both CPN and PPN. PPN resulted in subcutaneous infiltrations and more psychological trauma. PPN with enteral nutrition seems most appropriate for short term intravenous nutrition support or as a temporary substitute for CPN; CPN is preferred for long-term support.

Gastric teratoma: unusual cause for bleeding of the upper gastrointestinal tract in the newborn.

Bleeding of the upper gastrointestinal tract in the full-term newborn is a relatively benign and rare occurrence. This report describes a female infant with a gastric teratoma who experienced recurrent bleeding of the upper gastrointestinal tract as a neonate and infant secondary to gastric outlet obstruction. Anteroposterior and lateral abdominal radiographs revealed a large calcified abdominal mass with the pathognomonic features of a teratoma with a mandible and teeth. Gastric teratomas have not been previously reported as an etiologic or predisposing condition of gastrointestinal hemorrhage in two large reviews concerning this topic in the newborn and infant. This patient represents the 51st case and only the second female described in the literature. The frequency and unusual features of this treatable lesion, as well as the diagnostic approach to bleeding of the upper gastrointestinal tract in the newborn, are reviewed.

Efficacy of magnetic resonance imaging in 139 children with tumors.

One hundred thirty-nine children with neoplasms were studied using magnetic resonance imaging (MRI). This procedure was as accurate as computed tomography in predicting tumor histology, except that MRI was unable to detect small areas of tumor calcification. Magnetic resonance imaging could accurately identify the organ of origin of tumor masses and differentiate soft tissue from fat, fluid, or hemorrhage. In addition, MRI was helpful in planning surgery in many cases: It was better than computed tomography in defining the size and extent of soft-tissue tumor masses. It was accurate in defining the extent of the spread of bone sarcomas in the bone marrow. Without requiring the injection of intravenous contrast agents, it accurately defined displacement, encasement, or invasion of major abdominal blood vessels by Wilms' tumors and neuroblastomas. As a means of evaluating pediatric neoplasms, MRI is noninvasive, painless, and well tolerated by children, and it uses no radiation.

Nutritional support of children with neoplastic diseases.

There are numerous factors promoting the development of PEM in the child with cancer. Some of these factors are related to the tumor, many to the treatment itself, and some to failure of recognition of PEM. Not all children with cancer are at great risk for the development of PEM. These patients must be monitored and supported with comprehensive enteral programs. Children who have developed or are at risk for PEM must be identified and supported with CPN or PPN plus CEN during early intensive periods of treatment and during the later phases of abdominal radiotherapy, operative resection of tumor, or relapse. The decision to institute CPN must be based not only on the child's current nutritional status but also on the nature of the therapy he or she is soon to receive and the likelihood that he or she will be able to maintain an adequate intake during that therapy. Realistic goals must be set for nutritional support. The value of nutritional intervention lies in its ability to correct or prevent the development of adverse effects related to PEM. This support is hoped to contribute to improved tolerance of therapy, increased energy to complete normal day-to-day activities, and an improved sense of well-being for the child. If these goals have been accomplished, then the nutritional therapy has been successful.

Childhood neutropenia.

Neutropenia can occur because of abnormalities of marrow stem cell development, poor release of polymorphonuclear leukocytes from the marrow reserve, or decreased survival of polymorphonuclear leukocytes. Some of the more important clinical entities are discussed.

Rhabdomyosarcoma in childhood: analysis of survival in 98 cases.

Ninety-eight infants and children with rhabdomyosarcoma were analyzed for age, stage, site, and therapy as they relate to survival. Age and sex were not factors. Survival was 91% (10/11) for Stage I, 86% (13/15) for Stage II, 35% (12/34) for Stage III, and 5.2% (2/38) for Stage IV. Overall survival was 37% (37/98); however, 75% had advanced disease at diagnosis. Primary tumor site was genitourinary (GU) (31), extremity (17), head-neck (14), trunk (14), orbit (8), paratesticular (4), retroperitoneal (3), paraspinal (3), buttocks (3), and perianal (1). Survival was favorable in orbital, paratesticular, and (GU) sites. Survival was 20% (9/45) before and 52% (28/53) after chemotherapy and irradiation. The only survivors had embryonal cell histology. Tumor stage and site are important prognostic indicators. Chemotherapy improves survival in Stage I (91%) and Stage II (86%) and shrinks bulky Stage III tumors allowing less radical procedures in selected sites (e.g., GU). Survival is poor in Stage III (35%) and dismal in Stage IV (5.2%) despite combined therapy. Relapse was fatal despite attempts at second-look resection, and altered chemotherapy and irradiation.

The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Recently, much attention has been focused on the role of adjuvant chemotherapy in the treatment of osteosarcoma. Surgery, however, remains the primary modality for the ablation of this disease. In this report, we examine the relationship of various aspects of surgical management of osteosarcoma to prognosis for disease-free survival (DFS) in a randomized study of 234 pediatric patients. Attention is restricted to 166 patients with nonmetastatic disease confined to an extremity and who were randomized to receive one of two chemotherapeutic regimens. No advantage with respect to DFS was attributable to the various aspects of surgical management considered: interval from first symptoms to definitive surgery, surgical sequence, and type of surgery. Only two local recurrences were seen. One occurred in an above knee amputation stump and the other occurred in a patient receiving a tibial allograft. One of these patients died of pulmonary metastases within 6 months of recurrence; the other patient is alive without evidence of disease at last contact after resection of the recurrence followed by chemotherapy.

Bone scanning in management of metastatic osteogenic sarcoma.

Bone scan findings are presented from five consecutive cases of metastatic osteogenic sarcoma. Every patient had pulmonary metastases which concentrated the bone imaging radiopharmaceutical to some degree. In one patient, the diagnosis of pulmonary metastasis was made prior to our seeing any radiographic abnormalities. The mechanism by which skeletal imaging agents localize in pulmonary lesions is not clear. Unsuspected skeletal metastases were also discovered on scans in two patients, both of whom had normal radiographs. Diagnosis of hypertrophic pulmonary osteoarthropathy was made in one patient with normal radiographs. These findings indicate that bone scans as well as radiographs should be performed routinely in preoperative staging and followup of patients with osteogenic sarcoma.

Assessment of ventricular function in infants and children. Response to dobutamine infusion.

A method to assess ventricular functional reserve in infants and children unable to perform dynamic exercise was evaluated. Left ventricular ejection fraction was measured by radionuclide angiocardiography at rest and during infusion of dobutamine in 5-15 micrograms/kg/min dosages. The only side effects noted were arrhythmias in two patients, who had similar ectopy documented previously. Group left ventricular ejection fraction increased from 0.40 +/- 0.21 to a maximum of 0.49 +/- 0.24 (P less than 0.001). Left ventricular ejection fraction at 5 micrograms/kg/min (0.44 +/- 0.23) was not statistically different from that measured during infusion of dobutamine at 10 micrograms/kg/min (0.48 +/- 0.24). The six patients receiving anthracyclines, who had relatively low function at rest and increased function during dobutamine administration, were continued on their anticancer regimen without deteriorating in condition. Absolute values of left ventricular ejection fraction correlated best with the prognosis in patients with idiopathic dilated cardiomyopathy or structural abnormalities; six out of ten patients whose left ventricular ejection fraction never rose above 0.40 have either died or are in transplant protocols. Thus, study of left ventricular function can be performed easily during dobutamine infusion, generating valuable prognostic information.

Chemotherapy-associated Raynaud's phenomenon in a two-year-old girl.

Raynaud's phenomenon occurred in a 2-year-old girl 17 months after starting multiagent chemotherapy for an endodermal sinus tumor of the vagina. Symptoms began 2 months after receiving her final dose of bleomycin, and gradually resolved over a 6-month period despite continuing vinblastine. Chemotherapy-associated Raynaud's phenomenon appears to be unusual in young children, although mild episodes of vasospasm may not be reported by children or their parents. Specific questions regarding symptoms of Raynaud's phenomenon should be asked of all children receiving vinblastine and bleomycin therapy.

Isolated testicular leukemia following bone marrow transplant for acute lymphocytic leukemia. The need for pretransplant testicular biopsies.

Bone marrow transplantation has become an accepted mode of treatment for children with acute myelocytic leukemia in their first remission and acute lymphocytic leukemia after their first bone marrow relapse. Two-year survival rates of 50% can be achieved in patients undergoing transplant during remission, in contrast to a 2-year survival of 15% in those undergoing transplant while still in marrow relapse. Recurrence of bone marrow leukemia relapse is a significant cause of marrow transplant failure. Overt or occult testicular relapse occurs in 10-15% of males with acute lymphocytic leukemia receiving or having completed standard therapy regimens for control of their disease and frequently leads to a subsequent bone marrow relapse. This paper describes a child with acute lymphocytic leukemia who received a successful marrow transplant following bone marrow relapse and developed testicular leukemia relapse approximately 20 months after transplant. The experience with this child suggests that bilateral testicular biopsies should be a mandatory part of the routine evaluation to screen for residual leukemia before bone marrow transplantation.

The lack of correlation of gallium (67Ga) scans with known prognostic indicators in childhood acute lymphocytic leukemia.

67Gallium-citrate scans were performed on 45 patients with acute lymphoblastic leukemia (ALL) at the time of diagnosis. The extent of uptake and distribution of gallium were compared to known prognostic indicators of age, initial white count, and bone marrow lymphoblast immune markers (T, B, and null cell). Selective increased uptake was noted in bone, kidney, liver/spleen, lymph nodes, or other sites in 29 patients, and 16 patients had "normal" scans. A scoring system giving one point for selective uptake in each organ system was used. Patients were grouped according to scores of zero, 1--2, and 3 or greater. There was no significant correlation found between total gallium scores and any of the three prognostic indicators. There was also no significant correlation when prognostic factors were compared to uptake in the individual organ systems except that T cell disease was associated with a significantly greater propensity for lymph node uptake. There was a suggestion that children with "normal" gallium scans may have a better long-term prognosis, since 6 of 7 nonrelapsers observed for longer than 18 months had scores of zero at diagnosis compared to 4 of 6 early deaths with scores greater than zero. This study indicates that the 67Ga scan does not significantly correlate with known prognostic indicators, with the possible exception of lymph node uptake in T cell disease, and its value as an independent indicator of long-term survival will require longer follow-up.

Congenital monoblastic leukemia cutis. A case report with chromosomal abnormality: del (10p).

Congenital monoblastic leukemia cutis is a rare disorder. We report an infant who developed infiltrative skin lesions by 2 weeks of age, which, when biopsied at 4 1/2 months of age revealed a monoblastic infiltrate. Blasts in the peripheral blood were not seen until 1 week before her death at 8 months of age. Chromosomal analyses of her bone marrow showed an abnormal clone of cells with a 46,XX,del(10)(p12) karyotype. Although chromosome 10 is rarely involved in hematologic malignancies, abnormalities of this chromosome within the region 10p11-10p13 have now been shown in four of 10 reported cases of congenital monoblastic leukemia.

The value of nutrition support in children with cancer.

A positive stance towards nutrition support of the child with cancer assures potential for normal growth, development, and quality of life during extended oncologic treatment. Data from recent studies of children with cancer (advanced neuroblastoma, Wilms' tumor) demonstrate the importance of integrating nutrition staging, assessment, and support into treatment protocols. Patients with solid tumors and lymphomas who are malnourished at diagnosis have a poor outcome when compared to nourished counterparts. Enteral nutrition (intensive nutrition counseling and favorite, nutritious foods) is effective in low nutritional risk groups but ineffective in preventing or reversing protein-energy malnutrition in high nutritional risk groups. For high-risk groups, central parenteral nutrition is a relatively short-term, but important, support measure which allows children to grow despite extended periods of intense oncologic treatment. The patient's nutritional course may affect bone marrow suppression and the ability to tolerate aggressive chemotherapeutic treatment. Although treatment tolerance may be improved with nutrition support, adequacy of primary oncologic treatment outweighs other supportive factors as a determinant of ultimate survival.

Invasive aspergillosis of paranasal tissues in children with malignancies.

Paranasal aspergillosis was encountered in five children with relapsed malignancies. All had received broad-spectrum antibiotics within two weeks of development of aspergillosis, and all had absolute granulocyte counts less than 200/mm3 for at least three weeks. None had received prior antifungal therapy. There was an average delay of eight days before the correct diagnosis was established by either biopsy or culture. These data emphasize the need to obtain surveillance cultures of the upper respiratory tract passages in severely neutropenic patients receiving prolonged antibiotic therapy, and raise a question concerning prophylactic use of antifungal therapy in this group.

Methotrexate/L-asparaginase combination chemotherapy for patients with acute leukemia in relapse: a study of 36 children.

Cyclic administration of methotrexate (MTX) and L-Asparaginase (L-Asp) was utilized either as induction and maintenance chemotherapy or as maintenance chemotherapy alone following induction with other medications in treating 36 children with multiple relapses of acute leukemia. A complete remission rate (CR) of 67% was obtained in children with null-cell acute lymphocytic leukemia (ALL). The average length of remission was greater than four months. One of three patients with T-cell ALL and one of two patients with B-cell ALL achieved CR. In six cases of acute nonlymphocytic leukemia (ANLL), two patients achieved CR. One of two patients with terminal deoxynucleotidyl transferase (TdT) negative myeloblastic transformation of Ph'-positive chronic myelogenous leukemia (CML) obtained a CR lasting 20 weeks. Toxicity secondary to the chemotherapy included bone marrow suppression, hepatic injury, nausea, diarrhea, stomatitis, and allergic reactions to L-Asp. One case of subacute necrotizing leukoencephalopathy was seen.