The American journal of pediatric hematology/oncology最新文献

Purpose: Acquired inhibitors to coagulation factors are rare in pediatric patients. Exposure to topical bovine thrombin is a risk factor for the development of inhibitors in adult cardiac surgery patients. We report two pediatric patients who developed inhibitors to bovine and human factor V after exposure to fibrin glue containing bovine thrombin.

Patients and methods: The two patients, ages 3 1/2 years and 10 months, were studied after cardiac surgery. One patient had clinical bleeding. Coagulation factor assays and inhibitor studies were performed.

Results: The presence of a circulating inhibitor to bovine factor V was observed in both patients and to human factor V in one patient. The inhibition of bovine factor V interfered with standard assays for factor VIII activity using a commercial substrate fortified with bovine factor V resulting in spurious factor VIII deficiency. In one patient, an inhibitor of bovine thrombin was also identified. The inhibition of human factor V activity in one patient may have contributed to clinical bleeding.

Conclusions: Pediatric patients exposed to topical bovine thrombin, particularly in the setting of cardiac surgery, are at risk for the development of antibodies to bovine thrombin and factor V. This may also result in apparent but spurious depletion of other coagulation factors. These antibodies may cross-react with human coagulation factors, particularly factor V, resulting in clinical bleeding.

Purpose: In a prospective crossover study, we evaluated the safety and antiemetic activity of granisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, compared with conventional antiemetics regimen, including metoclopramide, in pediatric cancer patients.

Patients and methods: Twenty-two children with malignant diseases were enrolled. The chemotherapy included cytarabine 3 g/m2 (regimen A), cisplatin 90 mg/m2 (regimen B), and actinomycin D 900 micrograms/m2 plus ifosfamide 3 g/m2 (regimen C). Granisetron 40 micrograms/kg was infused over 30 min just before each chemotherapy treatment.

Results: A complete response was obtained more often with granisetron than with conventional antiemetics (59.1% vs. 0%, p < 0.001). In terms of efficacy by chemotherapy type, complete response with granisetron was obtained in eight of 10 patients with regimen A, three of eight with regimen B, and two of four with regimen C. Major efficacy (vomiting fewer than two times) was also obtained more with granisetron than with conventional antiemetics (81.8% vs. 4.6%, p < 0.001). The number of vomiting episodes in the first 24 h was less with granisetron than with conventional antiemetics (1.1 +/- 1.46 vs. 9.0 +/- 4.97, p < 0.001). Normal appetite and activity were retained in more patients with granisetron than with conventional antiemetics. Extrapyramidal reactions, akathisia, and sedation were not seen in any case with granisetron.

Conclusions: Granisetron 40 micrograms/kg is well tolerated and more effective than are conventional antiemetic regimens containing metoclopramide for children receiving cancer chemotherapy.

Purpose: The aim of the therapeutic trial was to try to optimize the treatment of severe and moderate aplastic anemia in children who lack a suitable bone marrow donor using the most successful available drugs, with the least amount of side effects.

Patients and methods: A pilot study for the treatment of severe aplastic anemia in children was conducted by four institutions. The treatment protocol included antithymocyte globulin (ATG), prednisone, and cyclosporine A. Twelve patients were enrolled, and 11 were evaluable. All patients had severe aplastic anemia (SAA); three had hepatitis-induced severe aplastic anemia (HI-SAA).

Results: Of 11 evaluable patients, eight have responded with normalization of their blood counts. Two of the three patients with HI-SAA responded to the therapy.

Conclusion: The results of our pilot study compare favorably with previous therapeutic trials. All the patients who responded achieved complete response, i.e., restoration of blood counts to within the normal range.

Purpose: Between 1975 and 1990, 13 patients seen at The Hospital for Sick Children, Toronto, Ontario, were noted to have concurrent idiopathic thrombocytopenia and neutropenia (ITN; platelet count < 150 x 10(9)/L; absolute neutrophil count < 1.5 x 10(9)/L). These patients all had normal marrow function and no evidence of systemic disease.

Patients and methods: A detailed chart review was performed to define the clinical and laboratory features of these patients.

Results: Although this was a heterogeneous group of patients, they shared several common characteristics. The disease followed a chronic course with thrombocytopenia or neutropenia or both that persisted or recurred over the entire period of follow-up in all patients (18 months to 15 years). The disease was associated with splenomegaly in eight patients and lymphadenopathy in nine patients. Boys were affected more frequently than were girls (ratio 11:2). Thrombocytopenia improved temporarily during treatment with corticosteroids, i.v. immunoglobulin G, RhoGAM, and a variety of immunosuppressive agents; however, neutropenia tended to be much more resistant to these therapies. Splenectomy was ineffective in two children in whom the procedure was performed. Platelet of and neutrophil antibodies or both were detected in five of six patients who were tested, suggesting an autoimmune cause for the cytopenias.

Conclusions: These findings suggest that ITN in childhood is distinct from immune thrombocytopenic purpura, particularly in terms of its chronicity and poor response to therapy.

Purpose: This study aims at defining the frequency and severity of late effects in a series of 288 long-term survivors of childhood cancer treated from 1962 to 1982 at the Giannina Gaslini Children's Research Hospital of Genoa, Italy.

Patients and methods: All cases with a diagnosis of malignancy in childhood and a minimum of 2.5 years from discontinuation of treatment were considered eligible. For all cases the study included physical, endocrinological, and psychological examination. Groups of patients selected according to treatment underwent cardiac, pulmonary, orthopedic, and ophthalmologic evaluation. The sequelae observed were scored according to a grading system in which asymptomatic subclinical defects are distinguished from those that are sufficiently symptomatic to require some type of corrective measure.

Results: Overall, 200 of 288 cases (69.4%) presented with some kind of abnormality. Symptomatic changes were present in 92 cases (42%); in these, severe and life-threatening late toxicity was reported in 61 (21.2%) and 12 cases (4.2%), respectively. The major risk factors appeared to be irradiation, type of tumor, and whether the patient had received therapy before 1974.

Conclusions: In our experience, this study demonstrates that there was a true excess of morbidity caused by the disease and its treatment in long-term survivors from almost any kind of childhood cancer. It also sheds light on how to prevent, diagnose, and adequately treat these patients and proposes specific criteria for the evaluation of the severity of delayed toxicity in long-term survivors of cancer in childhood.

Patient: A young boy with hyper-immunoglobulin M (IgM) syndrome had recurrent severe infections, failure to thrive, and chronic neutropenia for 2 years despite treatment with i.v. gammaglobulin (IVIG).

Methods and results: With the addition of granulocyte colony-stimulating factor (G-CSF; Filgrastim, Amgen, Inc., Thousand Oaks, CA), increased doses of IVIG, and prophylactic trimethoprim-sulfamethoxazole, his absolute neutrophil count increased from 0.64 x 10(9)/L to 3.36 x 10(9)/L, and he has been free of significant infection for the past 22 months.

Conclusions: The use of G-CSF merits consideration in patients with hyper-IgM syndrome and severe neutropenia.

Purpose: We describe a patient who presented with severe anemia and ectodermal dysplasia.

Patients and methods: This is a case report of a patient whose anemia was evaluated at New York Hospital and then returned to Australia where further testing was performed.

Results: The history indicated that this was a chronic anemia. Bone marrow examination showed binucleated late normoblasts consistent with congenital dyserythropoietic anemia type II (CDA II) and not dyskeratosis congenita. Paroxysmal nocturnal hemoglobinuria was excluded despite the presence of a positive sucrose hemolysis test. Other types of acquired and congenital anemias were excluded by testing.

Conclusions: This is the first patient reported with coincident CDA II and ectodermal dysplasia.

Purpose: We conducted a retrospective case-control study to examine the effect of granulocyte-colony-stimulating factor (G-CSF) on the duration of the neutrophil nadir and other clinical parameters in children with neuroblastoma.

Patients and methods: We retrospectively reviewed 85 courses of the same chemotherapy in 16 consecutive neuroblastoma patients. The first nine patients received no growth factor and the following seven patients received G-CSF. Data obtained included days of neutropenia, fever rate and duration, hospitalization rate and duration, antibiotic duration, and infection rate.

Results: Patients who received G-CSF had a significant decrease in the period of neutropenia (mean 5.4 +/- 2.6 days per course vs. 11.4 +/- 4.1 days per course in the control group; p < 0.001). There were no statistically significant differences in episodes of fever per course, rate of hospitalization per course, duration of hospitalization, or duration of antibiotic therapy. Control patients had documented infections during 16% (nine of 56) of their chemotherapy courses, whereas the patients receiving G-CSF had infections during 7% (two of 29) of their courses, but this difference was not statistically significant (p = 0.318). We calculated that a study of 220 courses in each group would be needed to have adequate power to confirm that this difference is statistically significant.

Conclusions: The administration of G-CSF in this patient population did result in fewer days of neutropenia, a finding that has been reported previously in several adult studies. However, we conclude that the clinical benefit of more rapid hematologic recovery in children remains uncertain and deserves further investigation in a large, prospective multicenter trial.

Purpose: The cytokine levels and the in vitro granulopoiesis were studied to evaluate the mechanism of impaired granulopoiesis in severe congenital neutropenia (SCN).

Patient and methods: The patient was a 5-year-old boy with SCN. We assayed the colony-stimulating activity (CSA) produced by peripheral blood (PB) cells from the patient. The plasma levels of cytokines were measured using enzyme immunoassay. These included granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor-alpha. The effects of IL-3 and stem cell factor (SCF) on the proliferation of granulocyte-macrophage colony-forming cells (GM-CFCs) were studied.

Results: CSA produced by PB cells from the patient was almost the same as in the healthy control. The level of endogenous G-CSF was elevated to 334 pg/ml, and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. The numbers of GM-CFCs were markedly depressed in the presence of G-CSF alone and showed no increment on additional stimulation by IL-3. SCF in combination with G-CSF significantly augmented the proliferation of GM-CFCs.

Conclusions: These findings suggest that some cytokines including G-CSF may be elevated in SCN patients and that CSF may play an important role in the pathogenesis of SCN.

Purpose: The Imerslund-Gräsbeck syndrome (IGS) is a rare inherited disorder characterized by a megaloblastic anemia due to a selective vitamin B12 malabsorption in association with a mild proteinuria. Usually recurrent infections, gastrointestinal complaints, and pallor are presenting symptoms. We report two cases of IGS with an unusual presentation.

Patients and methods: Two girls are described with the Imerslund-Gräsbeck syndrome who had a failure to thrive as a presenting symptom without infections or gastrointestinal complaints. The diagnosis of IGS was based on marked macrocytic anemia, very low serum vitamin B12 levels, abnormal Schilling urinary excretion test results, and mild proteinuria. When parenteral vitamin B12 was started, a rapid catch-up growth was seen in both girls.

Conclusions: The absence of well-known causes of failure to thrive, such as recurrent infections and gastrointestinal complaints, favors the concept that the metabolic disturbances caused by an isolated cobalamin deficiency as seen in IGS causes a failure to thrive.