Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials.

BACKGROUND: Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial. PATIENTS AND METHODS: We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method. RESULTS: Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25). CONCLUSIONS: Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

Pediatric hematology-oncology outreach for developing countries.

Health care in some developing countries is now at a level that makes programs for care of children with cancer feasible. Examples of successful international programs in this field include twinning programs, nongovernmental assistance organizations, such as the National Children's Cancer Society, and committees of professional organizations, such as the International Society of Pediatric Oncology (SIOP). The international outreach program at St. Jude Children's Research Hospital includes training programs within the hospital, partner sites in 13 countries, a school for Latin American nurses, a distance learning website, and telecommunications programs, which are described in detail. Future programs should be designed to maximize and evaluate impact, report accomplishments and failures, and avoid duplication.

Effect of malnutrition at the time of diagnosis on the survival of children treated for cancer in El Salvador and Northern Brazil.

PURPOSE: To investigate the relationship between survival and malnutrition at the time of diagnosis among children treated for cancer in two developing countries. PATIENTS AND METHODS: We studied 443 children treated for cancer between 1995 and 1998 at two centers in San Salvador, El Salvador, and Recife, Brazil. Median age at diagnosis was 4.9 years; 283 children had leukemia and 160 had solid tumors. Z-scores were calculated for weight for age (WAZ), height for age (HAZ), and weight for height (WHZ) at diagnosis. Z scores <-2 indicated malnutrition. Patients were also stratified by low-risk disease (solid tumors: stage I, stage II, or localized; acute lymphocytic leukemia: white blood cell count <25,000/microL, no central nervous system involvement, no mediastinal mass and age >1 and <10 yrs) and high-risk disease (all other patients, including those with acute or chronic myelocytic leukemia). RESULTS: Z-scores indicated malnutrition in 23.5% (WAZ), 22.8% (HAZ), and 15.7% (WHZ) of patients. Z-score was not significantly related to overall survival rates, to survival rates analyzed by type of malignancy or risk status, or to survival rates at the end of the first month of treatment. CONCLUSIONS: We found no relationship between nutritional status and survival in these patients. This implies that future protocols for use in developing countries can be designed to provide optimal treatment intensity despite the high incidence of malnutrition.

Granulocyte-macrophage colony-stimulating factor in the treatment of neonates with neutropenia and sepsis.

To evaluate the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in improving neutrophil counts and survival of neutropenic septic neonates, the authors studied 8 neonates with gestational or postconceptional age at least 30 weeks; weight at least 1000 g; serious infection with concomitant neutropenia (absolute neutrophil count [ANC] < 3.0 x 10(9)/L) or leukopenia (white blood cell count < 5.0 x 10(9)/L) and anticipated survival at least 48 h. Patients received 5 micrograms/kg of GM-CSF intravenously for 5 consecutive days or until the ANC reached 20 x 10(9)/L. Clinical parameters and complete blood counts were monitored. Prestudy ANCs ranged from 0.05 to 2.7 x 10(9)/L. Four patients had positive blood cultures, 4 had necrotizing enterocolitis, and 1 was in septic shock. All patients had elevated C-reactive protein. All patients had resolution of neutropenia and survived the septic episodes. The use of GM-CSF in these patients merits further exploration.

Pilot study of noninvasive detection of venous occlusions from central venous access devices in children treated for acute lymphoblastic leukemia.

BACKGROUND: Survivors of childhood acute lymphocytic leukemia (ALL) are at risk of venous occlusion induced by central venous access devices (CVADs). A sensitive, noninvasive screening technique to identify the magnitude of this problem is needed. Ultrasound (US) cannot always adequately image the innominate veins or the superior vena cava. Magnetic resonance angiography (MRA) can be noninvasive and may be useful for screening these patients. OBJECTIVE: We examined the suitability of US and MRA to identify venous occlusion. MATERIALS AND METHODS: We used MRA and ultrasound to examine 11 pediatric patients previously treated for ALL. CVADs had been in place a median of 2.5 years (range, 0.4-2.8 years) and removed a median of 2.1 years (range, 0.6-2.9 years) previously. We also performed 2D time-of-flight magnetic resonance angiography (TOF MRA) on two healthy young adult women with no history of venous abnormality or CVAD use. RESULTS: MRA suggested central venous abnormalities in 8 of the 11 ALL survivors and in both healthy control subjects. US results were negative in all 11 survivors. CONCLUSION: Further investigation is warranted to develop a sensitive and specific noninvasive method for identifying venous occlusion caused by prior CVAD use. Such a method would allow prospective studies of this complication in pediatric ALL survivors.

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

OBJECTIVE: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution. METHODS: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years). RESULTS: The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%. CONCLUSIONS: The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.

Factor V Leiden and other hypercoagulable state mutations are not associated with osteonecrosis during or after treatment for pediatric malignancy.

OBJECTIVE: Osteonecrosis (ON) is a debilitating complication of cancer treatment in children and is usually associated with systemic steroid therapy. Defects of coagulation may be important in the pathogenesis of ON. This study evaluated the prevalence of factor V Leiden (FVL, 1691G-->A), the most common inherited thrombophilic state, the prothrombin 20210G-->A polymorphism, and the thermolabile methylene tetrahydrofolate reductase (MTHFR, 677C-->T) variant in a group of children in whom ON developed during or after treatment for cancer. STUDY DESIGN: Children in whom ON developed during cancer treatment at St Jude Children's Research Hospital were studied (n = 24). Genomic DNA was isolated, and polymerase chain reaction was performed to identify the FVL, prothrombin 20210, and thermolabile MTHFR mutations. RESULTS: Sixteen of 24 patients had acute lymphoblastic leukemia. The mean age at ON diagnosis was 14.4 +/- 3. 7 years. The mean interval between cancer diagnosis and ON diagnosis was 27 +/- 21 months. Twenty-two patients had received steroids for a mean duration of 24 +/- 15 weeks before having development of ON. No patient had a history of thrombosis. Five (21%) patients had a family history of thrombosis. Genetic analysis revealed 0 (0%) of 24 FVL, 1 (4.5%) of 22 prothrombin 20210, and 3 (13.6%) of 22 thermolabile MTHFR. None of these mutation frequencies was significantly different from our control frequencies or published values. CONCLUSIONS: Although procoagulant abnormalities in general and FVL in particular have been detected in a significant number of patients with ON of the jaw and Legg-Perthes disease, we did not identify an increased prevalence of FVL or other hypercoagulable state mutations in a cohort of children with ON that developed during or after treatment for a variety of cancers.

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.

Transient erythroblastopenia of childhood associated with transient neurologic deficit: report of a case and review of the literature.

OBJECTIVE: Patients with transient erythroblastopenia of childhood (TEC) may also have a transient neurologic disorder. We present a case history and propose a mechanism for this syndrome. PATIENT AND METHODOLOGY: We describe a 20-month-old girl with TEC and transient hemiparesis. Records from the period January 1993 through December 1994 were reviewed to identify other patients with TEC and to determine whether neurologic deficits were noted in these cases. RESULTS: Of seven patients diagnosed with TEC over a 2-year period, only one had a neurologic deficit. This child's hemiparesis resolved within 24 h after the appearance of her symptoms. Her TEC resolved within 4 weeks, without long-term sequelae. Our experience and review of the literature suggest that focal neurologic deficits in TEC patients are uncommon, transient, lack long-term sequelae, and usually resolve prior to hematologic recovery. CONCLUSIONS: Previous reports suggested that the anaemia resulting from TEC might induce neurologic deficits. We suggest an alternative mechanism in which viral infection triggers a host immune response that independently leads to both TEC and neurologic abnormalities. Future studies should address the role of viral infection in TEC patients with focal neuropathies.

Renal medullary carcinoma: a potential sickle cell nephropathy of children and adolescents.

An extremely aggressive malignant epithelial neoplasm of the kidney has recently been described and named renal medullary carcinoma. The finding of this tumor is highly predictive of drepanocytes (sickle cells) in tissue sections and thus the presence of sickle hemoglobin, specifically sickle cell trait, in the patient. We present a case report of this rare tumor in a 10-year-old male. The tumor displayed a variable histologic architecture including gland-like areas with intra- and extracytoplasmic material resembling mucin with hematoxylin and eosin stain. This material was negative with periodic acid-Schiff and mucicarmine stains, stained only weakly with Alcian Blue, and was positive using antibodies against peanut agglutinin. Tumor cells stained positively with antibodies to epithelial membrane antigen, cytokeratin, vimentin, and Ulex europaeus lectin. The luminal face of tumor cells stained with peanut agglutinin. Stains using antibodies against carcinoembryonic antigen and alpha-fetoprotein were negative. Ultrastructurally, the tumor cells were characterized by short microvilli lining the luminal surface and lateral complex infoldings of adjacent plasma membranes. We discuss the relationship of this neoplasm to another renal pelvic neoplasm, collecting duct carcinoma, which may rarely occur in children. Renal medullary carcinoma should be included in the differential diagnosis of gross hematuria, which is most commonly benign self-limited hematuria, in young patients with sickle cell trait.

Mild hemophilia in children: prevalence, complications, and treatment.

PURPOSE: To review the natural history of mild hemophilia (factor VIII or IX level >5% and <50%), including presentation and diagnosis, characteristics of bleeding episodes, and therapy, at two hemophilia treatment centers. METHODS: Inpatient and outpatient records of 55 patients <17 years old with factor VIII or IX levels of 5 to 50% were reviewed and bleeding episodes for which medical attention was sought were analyzed. RESULTS: Five of the 55 patients were girls. Girls and patients with no family history of hemophilia were diagnosed at 5.5 and 5.3 years of age, respectively, compared to 2.8 years overall. Thirty-five patients were diagnosed because of a positive family history. No bleeding occurred in 18 patients; 190 bleeding episodes occurred in 37 patients. Most bleeding occurred in muscle/soft tissue (101 episodes) or joints (57 episodes) and were associated with trauma (174 episodes). CONCLUSIONS: Mild hemophilia may affect females more often than is appreciated. Delays in diagnosis and treatment may occur unless the variability in presentation is recognized.

Thrombopoietin level in young patients is related to megakaryocyte frequency and platelet count.

PURPOSE: To examine the relationships among platelet counts, bone marrow megakaryocyte frequency, and circulating thrombopoietin (TPO) levels. PATIENTS AND METHODS: TPO levels in 17 children and one young adult with chronic or recurrent thrombocytopenia were measured by ELISA and megakaryocyte frequency was analyzed by light microscopy. Three groups of patients were studied: Group I patients had aplastic anemia and absent or decreased megakaryocytes; Group II patients had intermittent periods of chemotherapy-induced thrombocytopenia; and Group III patients had normal or increased megakaryocytes. Controls consisted of 77 healthy adults. RESULTS: Patients in Group I had markedly increased TPO levels compared to normal controls. Their levels were significantly different (p = 0.03) from those of patients in Group III. The latter had normal or only mildly increased TPO levels except for one patient with myelodysplastic syndrome. Patients in Group II had markedly elevated TPO levels. After their bone marrow and platelet counts recovered from chemotherapy, their TPO levels decreased. In all three groups, a transient increase in platelet count (e.g., after platelet transfusion or anti-D immune globulin therapy) was associated with a moderate decrease in TPO. CONCLUSIONS: From this study, three conclusions can be made: 1) TPO levels are inversely related to megakaryocyte frequency; 2) platelet counts have a modest influence on TPO level; and 3) TPO levels may have clinical utility in diagnosis and management and further our understanding of the pathobiology of the disorders that cause thrombocytopenia.

Late vascular occlusion of central lines in pediatric malignancies.

OBJECTIVE: To determine whether thrombi or vascular occlusion represent a late complication persisting several years after removal of central venous lines (CVLs) in children and adolescents treated for childhood cancer. METHODS: Children whose treatment for malignancy included placement of a CVL that had been removed at least 2 months previously were studied during scheduled follow-up that included contrast-enhanced computed tomography. Spiral volume acquisition was used to obtain 3-mm images from the chest apices through the right hilum, and three-dimensional reconstruction of angiograms was performed. Thrombosis/occlusion was defined as narrowing, obstruction, or filling defect of the deep venous system, with or without the formation of collateral veins. Charts were reviewed to document patient characteristics, previous CVL complications, administration of hyperalimentation, use of urokinase, and family history of venous thrombosis. RESULTS: Twenty-three patients treated for solid tumors and 2 treated for B-cell acute lymphocytic leukemia or lymphoma were studied. Lines had been in place from 0.2 to 36 months (median, 7.4) and were removed at 2.3 to 121.8 months (median, 32.5) before study. Nine patients received hyperalimentation for periods ranging from 2 to 38 weeks (median, 12). Four patients had required urokinase instillations, and one developed superior vena cava syndrome; 4 had a CVL-related infection (two superficial and two Candida line infections). Occlusion was seen on computed tomography angiograms in 3 of the 25 patients (12%; 95% confidence interval: 4.5-31%). One of the patients with occlusion had superior vena cava syndrome; none had a family history of thrombosis, use of a double lumen CVL, or multiple instillations of urokinase. CONCLUSIONS: Persistent asymptomatic vascular occlusion does occur as a late complication of CVL placement for treatment of childhood malignancies, although the frequency appears low among patients treated primarily for solid tumors. Prospective studies of large numbers of patients with a broader spectrum of diagnoses are necessary to define the incidence of and risk factors for this complication and to assess the need for prevention with anticoagulation or other therapy. Pediatricians caring for patients with a history of cancer and CVLs should be aware that these patients may have persistent vascular occlusion that could predispose them to recurrent thrombosis or postphlebitic syndrome.

The effects of infusion rate on platelet outcomes and patient responses in children with cancer: an in vitro and in vivo study.

PURPOSE/OBJECTIVES: To determine the influence of infusion rate on quality of transfused platelets and patients' physical and subjective responses. DESIGN: Linked in vitro and in vivo studies with repeated measures and crossover designs, respectively. SETTING: A 52-bed pediatric cancer center in the midsouthern United States. SAMPLE: In vitro: 12 randomly selected platelet units. in vivo: convenience sample of 26 children, ages 3-20 years, with cancer and thrombocytopenia requiring platelet transfusion. METHODS: Four infusion rates studied in vitro: two infusion rates studied in vivo. MAIN RESEARCH VARIABLES: Platelet count, morphology score, corrected count increment, and patients' physical and subjective responses. FINDINGS: No clinically significant differences were found in outcomes across the four rates in vitro. Similarly, no statistically significant differences were found between the two in vivo rates on objective or subjective outcomes. CONCLUSIONS: In this setting, the more rapid infusion rate is clinically preferable because it does not negatively affect platelet recovery or patient outcomes and it decreases the infusion time by half. IMPLICATIONS FOR NURSING PRACTICE: Findings provided a basis for altering platelet infusion rates at the study setting. Benefits of the faster infusion rate include more rapid correction of thrombocytopenia, decreased time that outpatients must remain in the clinic for transfusion. Increased time available for other parenteral infusions in the impatient setting, and substantial savings in nursing time and associated costs.

Use of chest computed tomography in the staging of pediatric Wilms' tumor: interobserver variability and prognostic significance.

PURPOSE: To determine the specificity and prognostic significance of computed tomography (CT) of the chest in pediatric Wilms' tumor. PATIENTS AND METHODS: Patients treated for newly diagnosed Wilms' tumor at St Jude Children's Research Hospital between December 1978 and July 1995 were included in the study if an initial chest radiograph and CT were available and if pulmonary involvement (determined by chest radiographs) was absent. For the 202 patients studied, radiographs and CT scans were reviewed blindly and independently by three experienced radiologists for the presence of pulmonary nodules. Outcome variables consisted of intraobserver variability (in a subsample of 40 cases) and concordance between ratings on radiographs and CT scans (both by McNemar's test), interrater variability (by logistic regression), and the cumulative incidence of pulmonary relapse for patients with and without positive CT scans, by reviewer. RESULTS: As expected, ratings of pulmonary involvement on radiographs were discordant with CT ratings. There was marked variability among reviewers in CT ratings (P = .0001). Of 202 CT scans, 78 were read as positive by at least one reviewer, 41 were rated positive by only one reviewer, 18 by two reviewers, and 19 by all three. Intrarater variability on repeat reviews was not significant. Patients with nodules identified on CT had a significantly higher pulmonary relapse rate when analyzed separately by reviewer. However, for the 14 patients who had pulmonary relapse, CT scans were rated positive by all three reviewers in only five cases and as negative by all three in another five cases. CONCLUSION: The variability in interpretation of chest CT scans in patients with Wilms' tumor limits the predictive utility of these studies. Optimal, standardized techniques and central review are essential if chest CT is to be used for staging in cooperative studies.

Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease.

Streptococcus pneumoniae sepsis is the most common invasive infection among patients with sickle cell disease. The risk of a recurrent episode of sepsis and subsequent death in those patients who have had a previous septic event is much higher. Patients with sickle disease who have had pneumococcal sepsis should continue penicillin prophylaxis indefinitely and should not be candidates for out-patient management of febrile episodes.

Nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: We studied the prevalence of nasopharyngeal (NP) carriage, antimicrobial susceptibilities, and serotypes of Streptococcus pneumoniae (SP) in children with sickle cell disease (SCD) in the Mid-South. In addition, we examined risk factors for NP carriage of penicillin-resistant SP (PRSP). STUDY DESIGN: Between July 1994 and December 1995, we obtained NP cultures from 312 children with SCD followed at the Mid-South Sickle Cell Center, 208 (67%) of whom were receiving penicillin prophylaxis. RESULTS: Among the 312 patients, colonization with SP occurred in 42 (13%), 30 (71%) of whom were receiving penicillin prophylaxis. Twenty-three of the 42 SP isolates (55%) were resistant to penicillin; 5 of the 23 (22%) were highly resistant. PRSP organisms were also resistant to cefotaxime (43%), trimethoprim-sulfamethoxazole (57%), and erythromycin (22%). Serotypes 6A, 6B, 14, 19A, and 23F accounted for 19 (90%) of 21 resistant strains. Children who were treated with antibiotics during the preceding month were more likely to carry PRSP than children who were not treated. CONCLUSIONS: There is a high prevalence of NP carriage of PRSP in children with SCD in the Mid-South, which raises concerns regarding the continued effectiveness of penicillin prophylaxis in these children. Further studies on the antimicrobial susceptibilities of resistant organisms and the relationship between NP carriage of SP and invasive disease are needed before developing new recommendations for prophylaxis and treatment.

The factor V Leiden mutation in children with cancer and thrombosis.

Thromboembolic phenomena, frequently observed in children with cancer who are undergoing chemotherapy, can cause significant morbidity and, less frequently, mortality. Many contributory factors have been identified. Whether the recently identified and most common coagulation defect predisposing to thrombosis, factor V Leiden, is associated with thrombosis in this setting, has not been explored. The current study was undertaken to determine the prevalence of the factor V Leiden mutation in children with cancer who developed thromboembolic phenomena as compared to those with cancer who did not. Genomic DNA was amplified using the polymerase chain reaction (PCR), followed by digestion of the amplification product with the restriction enzyme MnlI. The digested PCR products were then size-fractionated to classify samples as heterozygous, homozygous or normal for the factor V Leiden mutation. 67 children with cancer were evaluated for the factor V Leiden mutation. One of 32 children with cancer and thrombosis, and none of 35 who had not experienced thrombotic problems, was found heterozygous for this mutation. We conclude that the factor V Leiden mutation does not play a significant role in the overall incidence of thromboses that occur in children with cancer.