Chemoimmunotherapy of acute leukemia in children.

Comparative results of chemo- and chemoimmunotherapy with Soviet strain of BCG vaccine in children with acute leukemia are presented. The immunotherapeutical regimen includes 20 intracutaneous injections of 0.1 mg BCG vaccine given weekly during 5--6 months with subsequent 5--6 months intervals simultaneously with maintenance chemotherapy. In the control group children were only given conventional chemotherapy. The median duration of remission and survival in patients who had received BCG chemoimmunotherapy was 25.2 +/- 1.5 and 32.3 +/- 1.2 months respectively. In the group of patients with chemotherapy alone--13.2 +/- 0.9 and 21.8 +/- 1.1 months respectively (p less than 0.01). The best results were obtained in children who had received before BCG immunotherapy neuroleukemia prophylactic treatment.     

Hepatic and splenic abscesses — a common complication of intensive chemotherapy of acute myeloid leukemia (AML)

Summary In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients:Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.     

Central nervous system leukemia in children with acute nonlymphoblastic leukemia

Factors contributing to the development of central nervous system (CNS) leukemia, and the impact of leukemic involvement of this site on subsequent remission length, were determined in 184 children with acute nonlymphoblastic leukemia who had been treated in two successive clinical trials. Preventive CNS therapy in both studies consisted of intrathecal methotrexate (12 mg/m2) given monthly during the first six months of therapy and then every three months until all treatment was stopped. Children with CNS leukemia at diagnosis or relapse were given intrathecal chemotherapy weekly for four weeks and then monthly throughout the remainder of the treatment course. Those continuing in complete remission received 2,400 rad cranial irradiation plus five doses of intrathecal methotrexate before cessation of therapy. The 38 children (20.7%) with CNS leukemia at diagnosis were more likely to have an initial leukocyte count greater than or equal to 25 X 10(9)/L (P = .01) and age less than 2 years (P = .03). The presence of CNS leukemia at diagnosis did not adversely affect the remission induction rate (P = .13) or the length of complete remissions (P = .73). CNS relapse ended initial remissions in 11 patients only and did not preclude subsequent long-term survival, as four of these children are off therapy and in second complete remission for 33+ to 78+ months. Three features at diagnosis were predictive of CNS relapse: monocytic or myelomonocytic leukemia (P = .002); age less than 2 years (P = .0001); and leukocyte count greater than or equal to 25 X 10(9)/L (P = .012). By stepwise Cox regression analysis, each factor was found to have independent predictive value. Despite the apparent effectiveness of intrathecal methotrexate as preventive CNS treatment, our findings indicate that more effective prophylaxis is needed for patients with features predisposing to CNS relapse.     

Emotional and behavioral symptoms in children with acute leukemia

BACKGROUND AND OBJECTIVES: The diagnosis of leukemia is probably one of the most severe stressors that children can experience and may be associated with emotional and behavioral symptoms indicating comorbidity with mental health disorders. This study aims to evaluate the presence of emotional and behavioral symptoms in children with acute leukemia exposed to chemotherapy from outpatient services at two university hospitals in Brazil. DESIGN AND METHODS: In this cross-sectional study, emotional and behavioral symptoms were assessed using the Children Behavior Checklist (CBCL) in three groups of children aged 5-14 years: a) children with acute leukemia (n = 21); b) children with blood dyscrasias (n = 21); c) children evaluated or treated in a pediatric outpatient service (n = 33). RESULTS: Children with blood dyscrasias had significantly few symptoms of externalization (delinquent and aggressive behavior) than pediatric controls (p< 0.05). Children with leukemia did not differ from the two other groups regarding symptoms of externalization. No significant difference on the scores of the CBCL internalization dimension (anxiety, depression, somatic symptoms and withdrawn) was found among the three groups. INTERPRETATION AND CONCLUSIONS: These findings seem to indicate that children with acute leukemia do not have more emotional or behavioral symptoms than children with benign hematologic or physical diseases suggesting that comorbidity with mental disorders is not higher in children with acute leukemia than in children in the other two groups.     

Chemotherapy of acute lymphoblastic leukemia in children.

Between 1969-1973, 75 consecutive children under the age of 15 years with acute lymphoblastic leukemia were treated with a multiple-drug regimen (L-2). Prophylaxis for meningeal leukemia was limited to the repeated intrathecal injections of methotrexate. Seventy-four patients achieved remission; the duration of remissions could be evaluated only for 70. Relapse terminated complete remission within 1-54 months in 21 children. Four of these relapses were confined to the central nervous system. Forty-nine patients continue in complete remission from 23 to 63 months. Chemotherapy has been discontinued in 29 children, and 25 of these remain without evidence of recurrence for 2-27 months posttreatment.     

Hepatic angiomyolipoma associated with splenic hamartoma

A 52-year-old woman was admitted to our hospital with thrombophlebitis of the internal jugular vein. Abdominal ultrasonography demonstrated a high echogenic mass measuring 4.5 cm in diameter in the liver, and abdominal CT revealed another liver tumor and an isodensity mass in the spleen. Abdominal MRI and angiography were performed and we presumed the tumors to be two hepatic angiomyolipoma and a splenic hamartoma. As an abdominal CT 21 months later revealed that all tumors were growing, these tomors were surgically resected. The histological diagnoses were hepatic angiomyolipoma and splenic hamartoma.     

Evaluation of cyclocytidine in children with advanced acute leukemia and solid tumors.

Cyclocytidine, a slow-release form of cytosine arabinoside, was evaluated in 69 children with advanced acute leukemia and solid tumors. One child with acute lymphocytic leukemia attained a complete remission. This child had received intrathecal cytosine arabinoside prior to the cyclocytidine. Eighteen of the 31 patients with acute lymphocytic leukemia/acute undifferentiated leukemia who did not respond received two or more courses of the drug. There were no responses in 15 children with acute myelogenous leukemia, in 11 children with neuroblastoma, or in 11 children with various solid tumors of childhood. A dose of 600 ng/m2/day for 10 consecutive days is tolerated in children.     

The periodic acid-Schiff reaction and prognosis in children with acute lymphoblastic leukemia.

We evaluated the intensity of the periodic acid-Schiff (PAS) stain reaction by examining 200 lymphoblasts from the initial marrow aspirate specimen of 38 children with acute lymphoblastic leukemia (ALL). The patients were separated into low, intermediate, and high groups according to mean PAS score. The groups were then compared in terms of age, sex, initial hematologic values, T- and B-lymphocyte markers, percentage of patients in remission six months after diagnosis, and percentage surviving. Significant differences were found between the low group and the other two groups with respect to sex, height of initial white blood cell (WBC) count, outlook for continued remission at six months, and overall survival (P < 0.05). The low-score patients were predominantly males, whereas the other PAS-score groups contained approximately equal numbers of males and females. The low-score patients had a higher median initial WBC than the others, but all three groups had a similar proportion of patients with initial WBC under 20,000/cu mm. Low-score patients were less likely to be in remission six months from diagnosis, and they had shorter survival than the intermediate- and high-score patients (P < 0.05). The results suggest that children with ALL whose lymphoblasts stain weakly with PAS have a worse prognosis than those with intermediate or high PAS reactivity. PAS reactivity may vary independently of the WBC at diagnosis in children with ALL, because children with a low PAS score have a poor outlook even with initial WBC under 20,000/cu mm.     

L-asparaginase in treatment of acute leukemia in children.

L-asparaginase from Escherichia coli--Crasnitin was used in 14 children with acute leukemia unresponsive to conventional treatment: 11 acute lymphoblastic leukemias, 1 acute myeloblastic leukemia, 2 other forms of leukemia. The remission induction was obtained in 70% of applications. Median of remission duration was 90 days. Serious side effects were observed. The validity of L-asparaginase in therapy of advanced childhood ALL is stressed.     

Transplantation for children with acute lymphoblastic leukemia

EFS for children with ALL continues to increase and is predicted to reach 90% with current therapy. Better understanding of leukemia cell biology and pharmacogenetics has led to the design of more effective treatment and also refined the prognostic features associated with a poor outcome. ALL characterized by the translocation t(9;22) or t(4;11), or by a hypodiploid karyotype or by an incomplete response to induction therapy is likely to relapse. SCT for ALL is largely used to treat patients failing primary chemotherapy but is selectively included as part of initial therapy for children at high risk for relapse. If SCT is going to become the primary therapy for children with ALL in first remission, the regimen-related mortality must approach 0%, and the risk for severe acute and chronic GVHD should be less than 5%. Salvage therapy after ALL relapse remains the major indication for SCT. The time required to find a suitable match has led to the use of cord blood and haploidentical related donors as stem cell sources. For children who relapse, SCT is likely to remain the principal option to promote survival. Efforts to reduce both the risk of relapse and the transplant regimen toxicity, both immediate and delayed, must continue.     

Oral health status in children with acute lymphoblastic leukemia

Leukemia is a malignancy of the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and accounts for nearly 75% of all newly diagnosed leukemias and 25% of all malignancies in childhood. The aim of the present study was to review the oral health status in children with ALL. Databases were explored using various combinations of the following keywords: "acute lymphoblastic leukemia", "children", "inflammation", "pediatric", "periodontal disease" and "periodontitis". Oral inflammatory conditions including chelitis, gingivitis, herpetic gingivostomatitis, mucositis, oral candidiasis, periodontitis and ulcerations are common manifestations in children with ALL. RESULTS: Periodontal inflammatory conditions and oral mucositis were reported to be significantly higher in children with ALL as compared to healthy controls. Tooth morphological disorders including agenesis, microdontia, short roots and developmental defects in the enamel and dentin were more often observed in children with ALL as compared to healthy controls. Children with ALL have a reduced salivary flow rate, which makes them more susceptible to dental caries as compared to healthy children. Malocclusion due to microdontia may also trigger temporomandibular joint disorders in children with ALL; however, this relationship needs further investigations. CONCLUSION: Oral inflammatory conditions including mucositis and gingivitis are common in children with ALL as compared to healthy children. Tooth morphological disorders including microdontia and enamel and dentin are common manifestations in children with ALL.     

Indications for platelet transfusion in children with acute leukemia

In an attempt to determine the indications for platelet transfusion in thrombocytopenic patients, we randomized 56 children with acute leukemia to one of two regimens of platelet transfusion. The prophylactic group received platelets when the platelet count fell below 20,000 per mm³ irrespective of clinical events. The therapeutic group was transfused only when significant bleeding occurred and not for thrombocytopenia alone. The time to first bleeding episode was significantly longer and the number of bleeding episodes were significantly reduced in the prophylactic group. The survival curves of the two groups could not be distinguished from each other. Prior to the last month of life, the total number of days on which bleeding was present was significantly reduced by prophylactic therapy. However, in the terminal phase (last month of life), the duration of bleeding episodes was significantly longer in the prophylactic group. This may have been due to a higher incidence of immunologic refractoriness to platelet transfusion. Because of this terminal bleeding, comparison of the two groups for total number of days on which bleeding was present did not show a significant difference over the entire study period.