Differentiation of bone infarct from infection in a child in sickle cell disease.
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Anemia, Sickle Cell↗
Biomedical subjects
G R Buchanan
Publications and source records attributed to G R Buchanan.
Barriers to bone marrow transplantation for sickle cell anemia.
While allogeneic marrow transplantation is curative therapy for patients with sickle cell anemia, only a small fraction of patients in the United States receive this treatment. We surveyed participants in our multicenter study of marrow transplantation for sickle cell anemia to determine reasons for not proceeding to transplantation. Among the 4848 patients less than 16 years of age with sickle cell anemia that were followed in 22 collaborating centers, 315 (6.5%) patients were reported to meet protocol entry criteria for transplantation, although there was wide variation among the institutions (0.9-36%). Among the 315 patients eligible for transplantation, 128 (41%) had human leukocyte antigen (HLA) typing performed, and of these 44 (14% of those meeting entry criteria) had an HLA-identical sibling. Common reasons for not proceeding with HLA typing in the remaining 187 patients included lack of a candidate sibling donor (76 patients, 24% of those meeting criteria) and lack of financial or psychosocial support (33, 10.5%). Parental refusal (30, 9.5%), physician refusal (13, 4%), history of medical noncompliance (2, < 1%), and other reasons (33, 10.5%) were less frequently cited. To date, 25 patients have been transplanted. Of the remaining 19 patients with HLA-matched donors, seven did not proceed to transplantation because of parental refusal, while the others anticipate a future transplantation (6), have experienced symptomatic improvement (4), or have relocated abroad (2). We conclude that the major barrier to marrow transplantation for sickle cell anemia is lack of an HLA-identical donor. But since only 6.5% of all children with sickle cell disease were considered eligible for transplantation, it is possible that other significant obstacles remain to be identified. For patients reported to meet eligibility criteria, parental refusal and limited financial or psychosocial support were infrequent barriers to transplantation.
Anemia, Sickle Cell↗
Conservative versus aggressive transfusion regimens in sickle cell disease.
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Anemia, Sickle Cell↗
Functional asplenia in hemoglobin SC disease.
The incidence of functional asplenia in sickle-hemoglobin C (SC) disease has not been defined, and the use of prophylactic penicillin to prevent life-threatening septicemia in this disorder is controversial. The percentage of red blood cells with pits (pit count) is a reliable assay of splenic function in other disorders but has not been validated in hemoglobin SC disease. To address these issues, we conducted a prospective, multicenter study of splenic function in persons with hemoglobin SC disease. Baseline clinical data were recorded, and red blood cell pit counts were performed on 201 subjects, aged 6 months to 90 years, with hemoglobin SC; 43 subjects underwent radionuclide liver-spleen scanning. Pit counts greater than 20% were associated with functional asplenia as assessed by liver-spleen scan, whereas pit counts less than 20% were found in subjects with preserved splenic function. Pit counts greater than 20% were present in 0 of 59 subjects (0%) less than 4 years of age, in 19 of 86 subjects (22%) 4 to 12 years of age, and in 25 of 56 subjects (45%) greater than 12 years of age. Other subjects with hemoglobin SC, who had previously undergone surgical splenectomy, had higher pit counts (59.7% +/- 9.5%) than splenectomized subjects without hemoglobinopathy (38.5% +/- 8.8%) or with sickle cell anemia (20.5% +/- 1.9%; P < .001). Two subjects with hemoglobin SC disease (not splenectomized), ages 14 and 15 years, with pit counts of 40.3% and 41.7% died from pneumococcal septicemia. These data indicate that functional asplenia occurs in many patients with hemoglobin SC disease, but its development is usually delayed until after 4 years of age. The pit count is a reliable measure of splenic function in hemoglobin SC disease, but values indicative of functional asplenia (> 20% in our laboratory) are higher than in other disorders. The routine administration of prophylactic penicillin to infants and young children with hemoglobin SC disease may not be necessary.
Adolescent↗
Bacteremia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia: is prophylactic penicillin necessary?
OBJECTIVE: To characterize the incidence of bacteremia and its potential for progression to septicemia in children with sickle hemoglobin C disease and sickle beta(+)-thalassemia to assess the need for penicillin prophylaxis. STUDY DESIGN: Retrospective chart review of the frequency and natural history of bloodstream infection in such patients not receiving prophylactic penicillin therapy and followed up in a single institution. RESULTS: During more than 842 patient-years of observation in 242 patients with sickle hemoglobin C disease, 15 episodes of bacteremia occurred in nine patients. Septicemia was fatal in one patient. The overall incidence of bacteremia, 1.8 events per 100 patient-years (95% confidence limits: 0.8, 2.8) in patients with sickle hemoglobin C disease, was similar to that in hematologically normal children. One episode of bacteremia occurred in a patient with sickle beta(+)-thalassemia. CONCLUSIONS: The incidence of bacteremia is not increased in young patients with sickle hemoglobin C disease and sickle beta(+)-thalassemia. Further, unlike its course in children with sickle cell anemia, it rarely evolves into life-threatening septicemia. This probably results from the maintenance of relatively intact splenic function during infancy and early childhood in patients with sickle hemoglobin C disease and sickle beta(+)-thalassemia. Prophylactic penicillin therapy may not be required in these patients.
Adolescent↗
High-dose intravenous methylprednisolone therapy for patients with Diamond-Blackfan anemia refractory to conventional doses of prednisone.
OBJECTIVES: To assess the efficacy and toxicity of very high doses of glucocorticoids in patients with congenital pure red cell aplasia (Diamond-Blackfan anemia) who did not respond to standard doses of prednisone. STUDY DESIGNS: We prospectively treated eight patients with transfusion-dependent Diamond-Blackfan anemia with high intravenous doses of methylprednisolone. All patients had previously not responded to one or more oral courses of prednisone in standard doses and were dependent on erythrocyte transfusions. Every patient initially received methylprednisolone at a dose of 30 mg/kg per day, followed by slow tapering for 4 weeks, but none responded. All patients then received a second treatment course starting at 100 mg of methylprednisolone per kilogram per day, again followed by slow tapering of the dosage. RESULTS: Three patients had a complete response that has been sustained for 21+, 31+, and 41+ months, respectively. One patient had a partial response. Toxic effects included a rise in serum alanine aminotransferase activity in all patients, transient diabetes mellitus in one child, and three episodes of bacteremia in two patients with intravenous access devices. CONCLUSIONS: We conclude that very high doses of methylprednisolone may induce sustained remission in some patients with transfusion-dependent Diamond-Blackfan anemia refractory to standard-dose prednisone therapy.
Adolescent↗
Risk of infection in children with hemoglobin S-beta-thalassemia.
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Bacteremia↗
Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II.
OBJECTIVE: To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Eighteen teaching hospitals throughout the United States. PATIENTS: Children with sickle cell anemia (hemoglobin SS or hemoglobin S beta 0-thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years. INTERVENTIONS: After randomization, patients received the study medication twice daily--either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months. MAIN OUTCOME MEASURES: The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo. RESULTS: Six children had a systemic infection caused by S. pneumoniae, four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%) with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group. CONCLUSION: Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia.
Anemia, Sickle Cell↗
Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia.
A 2-year-old boy with sickle cell anemia had a massive, fatal hemolytic reaction after administration of an intravenous dose of ceftriaxone. Laboratory studies demonstrated the presence of an IgM antibody against ceftriaxone, binding to and destroying the patient's erythrocytes by an immune complex mechanism. This rare complication should be considered in the differential diagnosis when hemoglobinuria develops in a child after administration of ceftriaxone or a similar agent.
Anemia, Hemolytic, Autoimmune↗
The changing epidemiology of bacteremia in neutropenic children with cancer.
Gram-positive bacteria have been the predominant organisms causing bacteremia in febrile neutropenic cancer patients during the past decade. Recently we have noted an increase in Gram-negative bacteremia in children and adolescents with cancer. Therefore we retrospectively reviewed 153 episodes of bacteremia during a 6-year period to investigate changes in the etiology of bacteremia in pediatric oncology patients. In the early 3-year period (January, 1988, to December, 1990) Gram-positive organisms comprised 73 (74%) of the 99 isolates, and Staphylococcus epidermidis was the most common isolate. In the later 3-year period (January, 1991, to December, 1993) Gram-negative organisms were seen with greater frequency and represented 50% of isolates (P = 0.004). Pseudomonas aeruginosa was the most commonly isolated organism during this period (22% of all isolates). We speculate that the recent utilization of more intensive chemotherapy regimens has caused an alteration in the epidemiology of bacteremia in children and adolescents with cancer which could influence the initial empiric antibiotic regimens and the outcome of such infections.
Adolescent↗
Bone marrow transplants from HLA-identical siblings as compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission.
BACKGROUND: It is unclear how best to treat children with acute lymphoblastic leukemia who are in a second remission after a bone marrow relapse. For those with HLA-identical siblings, the question of whether to perform a bone marrow transplantation or to continue chemotherapy has not been answered. METHODS: We compared the results of treatment with marrow transplants from HLA-identical siblings in 376 children, as reported to the International Bone Marrow Transplant Registry, with the results of chemotherapy in 540 children treated by the Pediatric Oncology Group. A preliminary analysis identified variables associated with treatment failure in both groups. We selected cohorts by matching these variables. A possible bias associated with differences in the interval between remission and treatment was controlled for by choosing matched pairs in which the duration of the second remission in the chemotherapy recipient was at least as long as the time between the second remission and transplantation in the transplant recipient. A total of 255 matched pairs were studied. RESULTS: The mean (+/- SE) probability of a relapse at five years was significantly lower among the transplant recipients than among the chemotherapy recipients (45 +/- 4 percent vs. 80 +/- 3 percent, P < 0.001). At five years the probability of leukemia-free survival was higher after transplantation than after chemotherapy (40 +/- 3 percent vs. 17 +/- 3 percent, P < 0.001). The relative benefit of transplantation as compared with chemotherapy was similar in children with prognostic factors indicating a high or low risk of relapse (the duration of the first remission, age, leukocyte count at the time of the diagnosis, and phenotype of the leukemic cells). CONCLUSIONS: For children with acute lymphoblastic leukemia in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy.
Adolescent↗
Safety and cost effectiveness of early hospital discharge of lower risk children with cancer admitted for fever and neutropenia.
BACKGROUND: Standard treatment for fever during periods of chemotherapy-induced neutropenia includes hospitalization and administration of intravenous antibiotics until the patient is afebrile and no longer neutropenic. This study prospectively evaluates the safety and cost-effectiveness of early discharge of selected low risk children before recovery from neutropenia. METHODS: We studied 74 children with cancer during 131 consecutive admissions for fever during a period of neutropenia. All patients initially were hospitalized and received broad-spectrum antibiotics. Intravenous antibiotic therapy was discontinued, and the patients promptly were discharged even if they had an absolute neutrophil count (ANC) of less than 500 cells/mm3 as long as they were afebrile, appeared clinically well, had negative cultures, exhibited control of local infection, and showed hematologic evidence of bone marrow recovery. RESULTS: Intravenous antibiotics were discontinued in 82 cases (63%) before recovery of the ANC to more than 500 cells/mm3, and 78 patients were discharged immediately. None of 70 patients discharged while neutropenic but exhibiting a rising ANC at the time of discharge developed recurrent fever and required readmission. Thirty of these children had an improving localized infection when intravenous antibiotics were discontinued and completed a course of oral antibiotics at home. The estimated mean savings in hospital charges due to early discharge was $5058 per patient. CONCLUSIONS: Low risk children with cancer who are hospitalized and treated for fever and neutropenia but appear clinically well may have intravenous antibiotics discontinued and be discharged safely irrespective of the ANC, as long as their granulocyte count is rising. This approach shortens hospital stays and results in considerable cost savings.
Adolescent↗
Recombinant alpha-2B interferon treatment for childhood T--lymphoblastic disease in relapse. A Pediatric Oncology Group Phase II study.
BACKGROUND: Children with chemotherapy refractory T-cell lymphoblastic leukemia/lymphoma were given alpha-interferon (alpha-IFN) to evaluate the efficacy and toxicity of this biologic response modifier. METHODS: Twenty children with T-cell acute lymphoblastic leukemia (T-cell ALL) in marrow relapse and one patient with mediastinal recurrence of T-cell non-Hodgkin's lymphoma (T-cell NHL) were enrolled. All patients had failed at least two previous multiagent drug trials. Recombinant alpha-IFN was given at 30 million U/M2/dose intravenously or subcutaneously for 10 doses over 14 days, followed by 3 doses per week until disease progression occurred. RESULTS: One child had a complete response (< 5% blasts) and three patients a partial response (5-25% blasts) in their bone marrow. All patients eventually showed signs of progressive disease. Significant toxicities included cardiac hypofunction in two patients and profound lethargy in two patients. CONCLUSIONS: alpha-IFN is tolerated in children with T-cell ALL and T-cell NHL and has activity against chemotherapy resistant disease.
Adolescent↗
High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease.
BACKGROUND AND METHODS: The management of episodes of severe pain in patients with sickle cell disease is a difficult clinical problem. We studied 36 children and adolescents with sickle cell disease who had 56 acute episodes of severe pain (44 in 27 patients with sickle cell anemia, 8 in 7 patients with sickle cell-hemoglobin C disease, and 4 in 2 patients with sickle cell-beta (+)-thalassemia). The patients were randomly assigned in double-blind fashion to receive an intravenous infusion of either saline placebo or high-dose methylprednisolone (15 mg per kilogram of body weight, to a maximum of 1000 mg) on their admission to the hospital and again 24 hours later. All the patients received intravenous morphine sulfate until severe pain abated and were then given acetaminophen with codeine. RESULTS: For all episodes of pain, the duration of inpatient analgesic therapy (intravenous and oral) was significantly shorter for the patients who received methylprednisolone than for those given placebo (mean, 41.3 vs 71.3 hours; P = 0.030). The difference was still significant (31.0 vs. 62.5 hours; P = 0.010) when we excluded seven episodes that were complicated by the chest syndrome (three in the methylprednisolone group and four in the placebo group). The patients who received methylprednisolone had recurrent episodes of pain shortly after the discontinuation of therapy more often than did the patients receiving placebo. No adverse effects of methylprednisolone were observed. CONCLUSIONS: A short course of high-dose methylprednisolone decreased the duration of severe pain in children and adolescents with sickle cell disease, but patients who received methylprednisolone had more rebound attacks after therapy was discontinued. On balance, corticosteroids are promising as an adjunct to supportive therapy for painful episodes in children and adolescents with sickle cell disease.
Adolescent↗
Implantable intravenous access devices in children with hemophilia.
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Adolescent↗
Treatment of advanced stage diffuse, small non-cleaved cell lymphoma in childhood: further experience with total therapy B.
Prior to the development of intensive treatments for patients with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL), the prognosis for such patients was dismal. A minority of patients attained long-term, disease-free survival. Since 1981, we have treated 28 children with advanced stage B-NHL with an intensive chemotherapeutic protocol, Total Therapy B. This regimen employs cycles of fractionated high-dose cyclophosphamide, doxorubicin, and vincristine alternating with sequential infusions of high-dose methotrexate and escalating doses of cytarabine, in addition to intensive intrathecal therapy. The planned duration of therapy is approximately 6 months. Two patients had B-cell acute lymphoblastic leukemia and 26 had stage III B-NHL; none had CNS involvement. The median age was 7 years. All 28 patients achieved complete remission (CR). Both patients with B-ALL and 21 of 26 with stage III B-NHL remain in CR, with a median follow-up of 51 months. Treatment failures included 3 patients with recurrent or progressive disease, 1 toxic death in CR, and 1 patient who developed a secondary mediastinal T-cell lymphoblastic lymphoma 4 1/2 years after the diagnosis of B-NHL. The 2- and 5-year event-free survival rates were 85.7 +/- 6.6% (SE) and 79.6 +/- 8.5%, respectively. Total Therapy B is a highly effective therapy for children with advanced stage B-NHL without CNS involvement.
Adolescent↗
Fatal pneumococcal septicemia in hemoglobin SC disease.
We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with hemoglobin SC disease. The earliest death occurred in a 1-year-old child who had congenital heart disease with cyanosis; the other children were aged 3 1/2 to 15 years. Only one child had received pneumococcal vaccine or prophylactic penicillin therapy. All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, < or = 3.6%). Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three. These cases illustrate that functional asplenia predisposes some children with hemoglobin SC disease to the development of fatal septicemia after the age of 3 years. We conclude that pneumococcal vaccine should be administered to all children with hemoglobin SC disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia. The routine use of prophylactic penicillin therapy in infants and children with hemoglobin SC disease remains controversial.
Adolescent↗
Treatment of childhood idiopathic thrombocytopenic purpura.
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Cerebral Hemorrhage↗