Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

VP-16-213, a semisynthetic podophyliotoxin, was tested for antitumor and clinical toxicity in 126 children. The drug was administered iv daily x 5 days every 2 weeks at a starting dose of 75 mg/m2/day. The dose was increased by 25 mg/m2/day/course until clinical response or significant toxicity occurred. The only major toxicity was hematologic, with neutropenia as the most predominant feature. There was one local allergic reaction at the site of injection. No systemic allergic responses were reported. The drug demonstrated significant activity in acute myelomonocytic leukemia with four responses among 19 patients, less activity in acute myelocytic leukemia with two responses among 44 patients, and little activity in acute lymphocytic leukemia with only one partial response among 12 patients. Objective partial responses occurred in ten of 48 patients with solid tumors: two each with Wilms' tumor, lymphoma, and histiocytosis X, and one each with rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, and undifferentiated carcinoma. The inclusion of VP-16-213 in combination chemotherapy for childhood acute myelomonocytic leukemia and acute myelocytic leukemia appears indicated in patients relapsing after initial therapy. For solid tumors this is an interim report, with further patient accrual required before specific comments can be made.
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PMID:Phase II study of VP-16-213 in childhood malignant disease: a Children's Cancer Study Group Report. 29 6

VM-26, a semisynthetic podophyllotoxin, was tested for antitumor activity and clinical toxicity in 181 children. The drug was administered iv at weekly intervals, beginning at a dose of 130 mg/2/week. The dose was increased, as tolerated, after 3 and 6 weeks to 150 and 180 mg/m2/week, respectively. The only major toxicity was hematologic, with neutropenia predominating. Anaphylaxis occurred in one patient. The drug demonstrated significant activity in acute lymphocytic leukemia (four responses among 15 patients) and neuroblastoma (ten responses among 31 patients). Objective responses were also noted in one patient each with acute myelogenous leukemia, Hodgkin's disease, histiocytic lymphoma, Wilms' tumor, Ewing's sarcoma, undifferentiated carcinoma, and sacrococcygeal sarcoma. Further trials of VM-26 in these childhood malignancies are warranted.
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PMID:Phase II study of VM-26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group. 38 Aug 3

To assess how well chemotherapy is tolerated after solid organ transplantation, we reviewed our experience at the Children's Hospital of Pittsburgh with five patients aged 1 to 12 years. Four patients had a liver transplant, indications for which were hepatoblastoma in two patients, hepatic failure secondary to Wilms' tumor chemoradiotherapy in one patient, and familial intrahepatic cholestasis in one patient. A fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium. After transplant, chemotherapy was given for the treatment of the primary malignancy in four of the patients. The patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression. All patients other than this patient were on immunosuppression with prednisone (0.5 to 2 mg/kg daily) and cyclosporine (to maintain serum levels at 800 to 1000 ng/ml radioimmunoassay) throughout the duration of chemotherapy. Courses of chemotherapy included one or more of the following agents: Adriamycin (Adr, 20 mg/m2 daily, three patients), Cyclophosphamide (Ctx, 1 gm/m2, one patient), cisplatin (CDDP, 90 mg/m2, one patient), Vincristine (Vcr, greater than 0.75 to 1.5 mg/m2, three patients), Actinomycin D (Act-D, 7.5 micrograms/kg, one patient), Ifosfamide (I, 1800 mg/m2, one patient) and Etoposide (VP-16, 100 mg/m2, one patient). All patients received greater than or equal to 3 courses (range, 3 to 9; mean, 5) of chemotherapy every 3 to 4 weeks. Dose reductions were made because of neutropenia in three patients but none were greater than 50%. Severe rejection was seen in one patient who had, however, manifested evidence of rejection prior to his first postoperative course of chemotherapy. No nephro or cardiac toxicity was seen. This preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation.
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PMID:Cancer chemotherapy after solid organ transplantation. 220 97

Children undergoing ABMT, a procedure which entails massive doses of chemotherapy along with total-body irradiation, are candidate to develop severe gastrointestinal toxicity and prolonged anorexia requiring administration of Parenteral Nutrition (PN) for variable periods. We report a series of 35 consecutive children affected by malignancies who underwent 37 courses of PN after ablative therapy followed by ABMT. Age ranged from 8 months to 17 years; 16 were females, 19 males. There were 23 cases of neuroblastoma, 5 of Wilms' tumor, 3 of acute myelogenous leukemia, 2 of Ewing's sarcoma, 1 case each of rhabdomyosarcoma and acute lymphoblastic leukemia. All patients developed severe neutropenia for 9-42 days (median 18 d). Fever occurred in all patients; sepsis was documented in 10. Duration of PN ranged from 10 to 64 days (23 +/- 9; mean +/- SD). PN solution, containing crystalline L-Aminoacids (8.5%) mixed with 33% glucose, minerals, trace elements and vitamins provided for children a caloric intake of 49.8 +/- 17.3 Kcal/Kg/day with a nitrogen intake of 0.26 +/- 0.27 g/Kg/day. Nutritional assessment, utilizing percent ideal body weight, serum protein electrophoresis, C3, pseudocholinesterase and fibrinogen, was performed at the beginning and at the completion of each course of PN. Mean percent ideal body weight was 95.8 before PN, 98.5 on last day of PN (p less than 0.0005). Other parameters did not change significantly. No metabolic complication nor severe electrolyte imbalance were observed except for 5 patients who developed hypokalemia in coincidence with administration of Amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Autologous bone marrow transplantation in children. Use of parenteral nutrition]. 311 38

Thirty-two children with poor-prognosis solid tumors were treated with a combination of high-dose cisplatin (CDDP) (200 mg/m2 over 5 days) and VP16. In the 30 children evaluable for antitumor effect, there were 7 complete, 12 partial, and 3 minor tumor responses. Wilms' tumor and rhabdomyosarcoma responded best. There were no therapy-related deaths. Severe neutropenia (PMN less than 500/mmc) developed after 29 out of the 45 evaluable courses and lasted a median of 8 days; during periods of neutropenia 8 episodes of fever occurred, 1 of which was caused by streptococcal sepsis. Platelet levels were depressed to less than 50,000/mmc after 17/45 cycles and this thrombocytopenia lasted a median of 8 days. No neurological toxicity occurred. One case developed acute renal failure. A hearing deficit for high frequencies was documented in 14/22 patients evaluated after the first cycle and in all cases after the subsequent cycles; the deficits correlated with the total dose of CDDP administered. High-dose cisplatin and VP16 is an effective association in children with advanced cancer, but cumulative dosage is limited by ototoxicity.
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PMID:High-dose cisplatin and etoposide in advanced malignancies of childhood. 315 39

During six-month period, 102 consecutive episodes of fever in 68 children (ranging from 1 month to 14 years of age) with malignant diseases were prospectively evaluated. Sixty-five had acute lymphoblastic leukemia, nine had acute myeloblastic leukemia, nine had malignant lymphoma (four Hodgkin and five non-Hodgkin), five had chronic myeloid leukemia, four had rhabdomyosarcoma, three had CNS tumors, two had neuroblastoma, one had Wilms, and four had other malignant tumors. Forty cases (39.2%) showed severe neutropenia (500 neutrophil/m3) during the episode. S. aureus, E. coli, and S. pyogenes were in 53% of the 75 microbiologic isolates. Twenty-two percent of the viral studies were positive. Mycologic studies were all negative, except one case with C. Albicans. Pneumonia (33 cases), cellulitis (15 cases), pharyngitis (12 cases), and varicella (11 cases) were the most common final diagnosis. Seventy-one percent of the episodes were etiologically documented (by bacterial isolate, characteristic serology, and/or typical clinic picture); 19% of the febrile episodes were probable infections, and 10% were fever of uncertain cause. Ninety percent of the cases responded well to therapy, and mortality of this series was 7%. Gentamicin, Carbenicillin, and Methicilin were the more common antibiotics employed. We conclude that in our population 1) infection is a frequent cause of morbidity in children with malignant diseases; 2) the most common cause of the febrile episodes is bacterial infection; 3) S. aureus, E. coli and S. pyrogenes are the most frequent bacterial isolates, and P. aeruginosa is infrequent; 4)viral infections are relatively frequent in this group of children; and 5) with adequate management, the mortality is low.
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PMID:Infections in children with malignant disease in Argentina. 722 35

Incidental appendectomy is frequently performed during nephrectomy for Wilms' tumor. The rationale for this approach is that the onset of appendicitis during a period of neutropenia after chemotherapy may cause increased morbidity. Additionally, children receiving chemotherapy or radiation therapy, or both, may experience abdominal pain, producing a diagnostic dilemma if the appendix is still present. We reviewed the charts of 1,910 children enrolled in the Third National Wilms' Tumor Study who underwent primary nephrectomy. Four hundred and fifty-five patients (23.8 percent) had appendectomy at the time of nephrectomy. An inversion appendectomy was performed upon 188 patients, and the appendix was excised in 267. Infectious complications and postoperative intestinal obstructions occurred with equal frequency in children who did or did not undergo appendectomy. The median follow-up period for the entire group of patients was 5.1 years. Only three of the 1,455 children (0.2 percent) who did not have an incidental appendectomy had appendicitis at two, seven and ten months after nephrectomy. None of the three children experienced any perioperative morbidity after appendectomy. These data suggest that incidental removal of the appendix is not essential for children undergoing removal of a Wilms' tumor.
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PMID:Incidental appendectomy during nephrectomy for Wilms' tumor. 838 58

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

Although limited data are available about topotecan disposition in patients with renal insufficiency, nothing has been reported in anephric patients. The objective of this report is to characterize topotecan disposition in an anephric child with Wilms tumor, both on and off hemodialysis. The patient received topotecan and cyclophosphamide for four cycles; topotecan was administered daily for 5 days, with hemodialysis on the second and fourth day. Therapy was well tolerated, with grade 3 thrombocytopenia and grade 2 neutropenia noted after cycle four. The median topotecan lactone clearance was 15.5 L/h/m off hemodialysis and 18.7 L/h/m on hemodialysis. Topotecan clearance was minimally affected by hemodialysis and was similar to that observed in children without renal failure.
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PMID:Topotecan disposition in an anephric child. 1534 88

Tumor necrosis factor (TNF), a peptide produced by macrophages with cytostatic and cytolytic effects, demonstrated single agent antitumor activity and synergistic effect when administered with dactinomycin in in vitro tumor cell lines, in vivo xenograft models, and adult and pediatric phase 1 clinical trials. This phase 2 pediatric trial evaluated the efficacy and further defined the toxicity profile of recombinant TNF (rTNF) and dactinomycin in patients with recurrent or refractory Wilms tumor. On this 2 stage Children's Cancer Group trial, dactinomycin (15 microg/kg/d, IV) immediately followed by rTNF (200 microg/m/d, IV), once daily for 5 consecutive days, was administered to patients with recurrent or refractory Wilms tumor. Cycles repeated every 21 days to a maximum of 12 courses. Nineteen of 21 consecutive patients, ranging 0.9 to 16.5 years of age at the time of initial diagnosis, were evaluable for response and toxicity. Three patients (15.8%) had a complete response, 5 (26.3%) had stable disease, and 11 (57.9%) had progressive disease. Following 59 patient treatment cycles, the most commonly observed grade 3/4 toxicities were thrombocytopenia (40.7%), elevated liver transaminases (23.7%), neutropenia (20.3%), leucopenia (13.6%), anemia (11.9%), and myalgias (10.2%). Before completion of stage 2, the study closed due to unavailability of rTNF. The documented complete responses and disease stabilization suggest antitumor activity of rTNF with dactinomycin in patients with recurrent Wilms tumor. The combination was well tolerated. Although grade 3/4 adverse events were reported, dose adjustments were not required. Toxicities resolved without significant interventions.
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PMID:Phase 2 trial of recombinant tumor necrosis factor-alpha in combination with dactinomycin in children with recurrent Wilms tumor. 1860 Jan 76


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