Fatal pulmonary hemorrhage associated with micrococcal infection in two children with acute lymphoblastic leukemia

Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia. Within a 2-month period the authors observed two fatal pediatric cases, which were associated with opportunistic organisms of the genus Micrococcus. Both patients were receiving consolidation treatment for acute lymphoblastic leukemia. The authors discuss the causes of pulmonary hemorrhage in patients with leukemia and review the relevant literature. Micrococci have previously been considered as non-pathogenic, but there is considerable evidence for morbidity and mortality occurring, particularly in immunocompromised patients. The authors propose that micrococcal infection may have been a major predisposing factor for pulmonary hemorrhage in these thrombocytopenic patients.     

Fatal Fournier's gangrene in a young adult with acute lymphoblastic leukemia

Fournier's gangrene (FG) is a fulminant necrotizing fasciitis of the external genitalia. Few reports of FG exist in patients with hematologic malignancies. We describe a case of fatal FG in a 21-year-old man with acute lymphoblastic leukemia who was receiving remission-induction chemotherapy. Despite early local surgery, administration of appropriate antibiotics, resurgery for wider debridement and aggressive ICU support he succumbed while pancytopenic to septic shock, 26 days after initiation of chemotherapy. Multi-drug resistant Pseudomonas aeruginosa was isolated from blood and scrotal cultures obtained at initial surgery. FG is a fulminant infection, especially in the face of profound cytopenias.     

XYY syndrome in children with acute lymphoblastic leukemia

Certain constitutional chromosomal abnormalities increase the risk of malignancy and/or decrease treatment tolerance. We identified two patients with the XYY syndrome among a total of 444 male children with acute lymphoblastic leukemia who had complete cytogenetics studies. In both cases, the leukemic cell karyotype suggested a constitutional XYY abnormality that was confirmed in studies of lymphocytes obtained during remission. The incidence rate in our series is higher than that of the XYY syndrome in the general population (0.0045 vs. 0.001), but not significantly so. This finding and a literature review failed to confirm an increased frequency of the XYY syndrome among children with acute lymphoblastic leukemia. Both of our patients remain in remission 24 and 28 months, respectively, postdiagnosis. Their tolerance of intensive treatment, including high-dose methotrexate, suggests that the untoward treatment toxicity seen in patients with chromosomal abnormalities such as trisomy 21 does not extend to the XYY syndrome. © 1997 Wiley-Liss, Inc.     

Human bocavirus in children with acute lymphoblastic leukemia

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.     

Cytomegalovirus disease in children with acute lymphoblastic leukemia

Viral infections are an underrecognized problem in children on standard chemotherapy for acute lymphoblastic leukemia (ALL). In countries with high baseline seroprevalence of cytomegalovirus (CMV) such as India, it may be an important pathogen leading to fever, end-organ damage, and cytopenia. Data regarding the incidence and manifestations of CMV disease in pediatric ALL patients are scanty. The authors prospectively assessed all children on chemotherapy for ALL with prolonged febrile neutropenia (FN) for CMV disease over a 3-year period. Children with end-organ damage, including pneumonia, retinitis, and colitis, were also evaluated. Quantitative and qualitative polymerase chain reaction (PCR) from blood, body fluids, or tissue was done along with ophthalmologic evaluation. CMV disease was detected in 10% of the children with prolonged FN. In addition, other children were identified due to end-organ damage, lung and eye being the common organs of involvement. Time of CMV reactivation was essentially during nonintense phase of chemotherapy. Lymphopenia was present in most children, and prolonged lymphopenia was associated with relapse of CMV infection after therapy. The authors conclude that CMV is an important pathogen in children on standard chemotherapy for ALL. It has a good outcome with early detection and directed therapy. Parenteral ganciclovir is needed for a period of 14–21 days to prevent recurrence.     

Vincristine disposition in children with acute lymphoblastic leukemia

Vincristine (VCR) has been widely used to treat childhood malignancies for over thirty years, but its plasma disposition has not yet been well-defined. Therefore, we conducted a pharmacokinetic study of VCR in 17 children with acute lymphoblastic leukemia (ALL) receiving the first dose of VCR. A new high-performance liquid chromatographic assay was used for the measurement of VCR in plasma. A two-compartment pharmacokinetic model was fit to the data by nonlinear least-squares regression. Estimated pharmacokinetic parameters were highly variable; mean (S.D.) volume of distribution at steady-state was 360 (176) L.m^?2; total body clearance was 431 (238) ml. min^?1.m^?2, and elimination half-life was 823 (390) min. These results were compared to data from eight adults with lung cancer. Mean volume of distribution in adults and children were similar, but VCR clearance was significantly larger in children (P = 0.01), resulting in a significantly longer elimination half-life in the adults (P < 0.01). We conclude that administration of a standard dosage of VCR to children with ALL results in a highly variable systemic drug exposure, which may have implications for the oncolytic effect and/or toxicity in individual patients. Comparison of data from children and adults suggests that VCR elimination rate is a function of age; this could account for more severe neurotoxicity in older patients. However, it cannot be excluded that differences between the children and adults may be due to other variables than age. Future studies should focus on the possible influence of multidrug resistance modulating agents on VCR pharmacokinetics and on pharmacokinetic-pharmacodynamic relationships in individual patients. © 1995 Wi1ey-Liss Inc.     

Neutropenic enterocolitis in children with acute lymphoblastic leukemia

Neutropenic enterocolitis is an acute, life-threatening inflammation of the small and large bowel, often seen in children with malignancies during periods of prolonged or severe neutropenia. During the period 1990-1995, 180 children were treated at the authors' center for acute lymphoblastic leukemia using a standard chemotherapy protocol. Among them, 11 children (6.1%) aged 4 to 12 years, were diagnosed clinically to have neutropenic enterocolitis. Eight had severe neutropenia (absolute neutrophil count < 10(8)/L and 5 had prolonged neutropenia (> 7 days duration). The symptoms included diffuse abdominal pain (10 children), oral mucositis (7), hematochezia (7), diarrhea (6), hematemesis (5), and right lower quadrant tenderness (4). Three children had radiological evidence of free intraperitoneal gas and an additional 3 children were found on surgical exploration to have cecal perforation. Laparotomy was performed on 8 children (73%), 4 of whom survived. Among the 3 children managed conservatively, 1 died awaiting surgical exploration, while the other 2 did well. The overall survival was 55%. The authors recommend an approach to management that respects the heterogeneity of the disease.     

Acute respiratory illness in children with acute lymphoblastic leukemia

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.     

Transient hyperglycemia in Hispanic children with acute lymphoblastic leukemia

BACKGROUND: Transient hyperglycemia occurs commonly during the treatment for childhood acute lymphoblastic leukemia (ALL). The purpose of this study was to examine the incidence of and risk factors for transient hyperglycemia during induction chemotherapy in Hispanic pediatric patients diagnosed with B-Precursor ALL. PROCEDURE: The study cohort consisted of 155 Hispanic pediatric patients diagnosed with ALL and treated at one of two South Texas pediatric oncology centers between 1993 and 2002. Hyperglycemia was defined as > or = 2 glucose determinations of > or = 200 mg/dl during the first 28 days of induction chemotherapy. RESULTS: Overall, 11.0% of the study cohort developed transient hyperglycemia during induction chemotherapy. Age and body mass index (BMI) were both positively associated with the risk of hyperglycemia. Females exhibited a substantially higher risk of hyperglycemia than males, but this association did not reach statistical significance after adjusting for other covariates. Among patients who developed hyperglycemia, 100% of those who required insulin were in the 13-18-year age group and reported a family history of diabetes. Hyperglycemic patients classified as obese (BMI > or = 95 centile) were more than twice as likely to have required insulin therapy compared to overweight patients (BMI 85-<95 centile) and three times as likely to have required insulin compared to normal weight (BMI < 85 centile) patients. CONCLUSIONS: The incidence of chemotherapy-induced transient hyperglycemia in the present study cohort is comparable to that reported in previous pediatric ALL patients. This finding is interesting in view of the elevated prevalence of obesity and the underlying dietary behaviors in this Hispanic study cohort.     

Predictable risk factors in children with acute lymphoblastic leukemia

The predictable prognostic factors were analysed among 174 children with acute lymphoblastic leukemia who were treated during the last ten years under different protocols in one institute. It was confirmed that the children under 1 year of age, or with T-cell marker, had poor prognosis. The initial WBC of more than 50,000/mm3 was less significant as a predictable risk factor with chemotherapy of the newer protocols. Cell kinetic study was found to be of no more help than the initial WBC, but a more accurate prediction could be obtained by measuring glucocorticoid receptor of leukemic cells. The prognosis was poor among children with initial WBC of more than 50,000/mm3 and receptors of less than 20,000 sites per cell.     

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug‐supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.     

Acquired X-chromosome aneuploidy in children with acute lymphoblastic leukemia

BACKGROUND: A cytogenetic study of 75 consecutive children with ALL revealed a normal karyotype, a low hyperdiploid karyotype (including 47-50 chromosomes), and a high hyperdiploid karyotype (including > 50 chromosomes) in 10, 12, and 33 patients, respectively. An acquired extra X-chromosome was detected at diagnosis by conventional cytogenetics in 29 (88%) of 33 children with a high hyperdiploid karyotype and in 4 (33%) of 12 children with a low hyperdiploid karyotype. X-chromosome aneuploidy was retrospectively studied by fluorescence in situ hybridization (FISH) in eight and 20 patients with a normal and a hyperdiploid karyotype, respectively. PROCEDURE: A classical cytogenetic study was performed according to standard methods. FISH with the centromeric probe specific to X-chromosome was used to study interphase cells of bone marrow or blood samples. RESULTS: An extra X-chromosome was found by FISH in all 13 patients with a high hyperdiploid or tetraploid, in 6 of 7 patients with a low hyperdiploid, and in none with a normal karyotype. Two children with a normal karyotype displayed monosomy X. Altogether, 57.3% of newly diagnosed children displayed X-chromosome aneuploidy. CONCLUSIONS: Out study indicates that X-chromosome aneuploidy may be the most common chromosome abnormality in childhood ALL. It can be detected in nearly all children with a high hyperdiploid karyotype and up to one-half of the patients with a low hyperdiploid karyotype. FISH with an X-chromosome centromeric probe is a rapid and simple tool to detect an abnormal clone at diagnosis in the majority of children with ALL and is useful in confirming remission in these patients.