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)

In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively in order to identify the optimal conditions required for a rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve > or = 0.5 x 109/l neutrophil count after alloBMT was 17 (median 17, range 9 to 27 days) and 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. The haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Furthermore, 50% and 40% of patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg/day G-CSF had rapid neutrophil recovery within 15 days after alloBMT, versus only 7.1% of patients not receiving G-CSF post-transplant (n = 28), p < 0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either TBI-containing or busulfan-containing conditioning regimen. A significant correlation was found between neutrophil recovery and either the MNC or CFU-GM content of the allografts, r = 0.33, p < 0.01. The mean number of days required for neutrophil recovery was only 16 days (median 16, range 9 to 24 days) in patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28) versus 19 days (median 19, range 13 to 27 days) in patients receiving allografts containing < 1 x 10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing less than 0.5 x 10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve 20 x 109/l platelet count was 21 (median 20, range 11 to 50 days) and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not significantly affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was only 20 days (median 18 days) in patients receiving allografts containing > 1.0 x 10(5) BFU-E/kg (n = 35) versus 23 days (median 20 days) in patients receiving allografts containing < 1.0 x 10(5) BFU-E/kg (n = 24). Seven patients receiving allografts containing less than 0.5 x 10(5) BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF post-transplant as the optimal combination for a rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant factor to determine platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery and longer period of fever during neutropenia and hospitalisation.
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PMID:Factors influencing the haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis: a single-centre experience. 906 85

Daily 6-mercaptopurine (6MP) forms the backbone of continuing chemotherapy for childhood lymphoblastic leukaemia (ALL). A major metabolic route is catalysed by thiopurine methyltransferase (TPMT). TPMT deficiency occurs in 1 in 300 individuals and results in high concentrations of thioguanine nucleotides (TGNs), cytotoxic 6MP metabolites. A leukaemic child taking 6MP repeatedly developed profound pancytopenias. TPMT deficiency was confirmed. TGN formation was then studied on attenuated 6MP dosages. Four weekly oral doses of 75 mg/m2 6MP produced TGNs of 2348 pmol/8 x 10(8) red cells, nearly double the maximum TGNs recorded in ALL children with TPMT activity taking long term daily 75 mg/m2 6MP. Grossly elevated TGN concentrations were also produced at 10% standard 6MP dosage (7.5 mg/m2 daily), accompanied by unacceptable 6MP toxicity (neutropenia, diarrhoea, vomiting). The child was eventually stabilised on 10% alternate day therapy and after 15 weeks TGNs were 1670 pmol, just above the upper end of the TGN range for ALL children with TPMT activity.
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PMID:Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6-mercaptopurine dosage strategies. 925 29

In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively to identify the optimal conditions required for rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve a neutrophil count > or = 0.5 x 10(9)/l after alloBMT was 17 (range 9-27), 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. Haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Also, 50% and 40% of patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg G-CSF per day, respectively, had rapid neutrophil recovery within 15 days after alloBMT, as against only 7.1% of patients not receiving G-CSF after the transplant (n = 28); P < 0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either a TBI-containing or a busulfan-containing conditioning regimen. A significant correlation was found between the neutrophil recovery and either the MNCs or CFU-GM contents of the allografts. The mean number of days required for neutrophil recovery was only 16 (range 9-24) in patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28), as against 19 (range 13-27) in patients receiving allografts containing < or = 1 x 10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing < 0.5 x 10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve a platelet count > or = 20 x 10(9)/l was 21 (range 11-50), and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was 20 in patients receiving allografts containing > 1.0 x 10(5) BFU-E/kg (n = 35), as against 23 days in patients receiving allografts containing < or = 1.0 x 10(5) BFU-E/kg (n = 24). Seven patients receiving allografts containing < 0.5 x 10(5) BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF posttransplant as the optimal combination for rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant determining factor in platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery, a longer period of fever during neutropenia and longer hospitalization.
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PMID:Factors influencing haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis. A single-centre experience. 925 26

Advances in the molecular and immunologic characterization of leukemic cells have greatly aided the diagnosis and risk assignment of ALL, as well as the monitoring of bone marrow samples for minimal residual disease. Currently, 75% of childhood cases have biologically and therapeutically relevant genetic abnormalities. Although gene discoveries in ALL have not been directly translated into effective therapy, there is every reason to believe that this disease will eventually yield to molecular intervention. In the meantime, efforts are being made to enhance the efficacy of existing regimens while reducing their toxic side effects. We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. The challenge now is to identify specific treatments for genetically defined subtypes of ALL.
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PMID:Acute lymphoblastic leukemia. 928 87

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.
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PMID:Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation. 933 54

We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.
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PMID:Recipients and donors of bone marrow transplants suffering from Chagas' disease: management and preemptive therapy of parasitemia. 950 74

We sought to determine the role of granulocyte colony-stimulating factor (G-CSF) as an adjunct therapy in high-dose cytarabine-containing chemotherapy (HD C/T) for children with acute leukemia. Seventeen patients, aged 9 months to 18 years old, 8 ALL and 9 AML, were treated with cytarabine (Ara-C) 1 g/m2 q12h for 8 doses with mitoxantrone, idarubicin, VP-16, or asparaginase. A total of 71 courses of HD C/T was given. G-CSF was not used in 14 courses (Group A). Prophylactic G-CSF was given in 57 courses (Group B) as 200 microg/m2/d SC started one day after the completion of HD C/T and continued until the neutrophil recovery was maintained. The incidences of sepsis per course in Group A and Group B were 35.7% (5/14) and 40.4% (23/57), respectively. While 2 patients in Group A died of sepsis or pneumonia, none in Group B died. The mortality and delay in chemotherapy were fewer in Group B (P = 0.037 and 0.0006, respectively, Fisher exact test). There was a shorter average number of days of neutrophil <500/cumm, antibiotic usage, fever, and hospital stay in Group B (11, 8, 5, 17 days in Group B vs. 21, 17, 10, 37 days in Group A; P = 0.0001, log-rank test; 0.0006, 0.0023, 0.0001, Wilcoxon rank sum test, respectively). The incidence of neutropenic fever was lower in Group B, but the difference did not reach statistical significance (P = 0.06, Fisher exact test). We conclude that G-CSF as an adjunct therapy in HD C/T is effective in reducing mortality, days of neutropenia, antibiotic usage, fever, hospital stay, and frequency of delay in chemotherapy. The efficacy of this treatment approach requires further testing in a randomized, controlled trial.
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PMID:High-dose cytarabine-containing chemotherapy with or without granulocyte colony-stimulating factor for children with acute leukemia. 959 Jan 44

The therapeutic benefit of G-CSF in the treatment of acute lymphoblastic leukemia has been well established. G-CSF has been used to shorten neutropenia induced by conventional dose cytotoxic chemotherapy and allogeneic bone marrow transplantation. Recently autologous peripheral blood progenitor cell transplantation has been explored to treat high-risk ALL. Several in vitro studies suggest that subpopulations of lymphoblasts express G-CSF receptors. Furthermore, enhanced growth of Ph+ ALL cells expressing myeloid antigens stimulated by G-CSF has been demonstrated in vitro. However, the clinical relevance of these findings has been questioned. We report a patient with my+Ph+ALL in whom the administration of G-CSF after high-dose Cytarabin and Mitoxantrone led to a significant mobilization of leukemic cells and contamination of the stem cell harvest during cytologic marrow remission.
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PMID:Granulocyte colony-stimulating factor (G-CSF) mediated mobilization of leukemic cells in Philadelphia chromosome positive acute lymphoblastic leukemia expressing myeloid antigens (my+Ph+ALL). 969 99

The nutritional status of a child on cancer therapy influences both tolerance of and response to treatment. However, it is difficult to assess nutritional status on a daily basis because an accurate quantitation of the calorie intake is difficult. Anthropometric and biochemical parameters are prone to error and often reflect past rather than current nutritional status. In practice, a subjective clinical assessment is usually relied upon. This study objectively appraises the value of such an assessment. Based on clinical symptoms that alter oral intake and absorption of food, a scoring system was designed to assess nutritional status on a day to day basis. A symptom score (SS) of 10 implied "normality"; 0 indicated maximum debility. Over a 2-year period 511 daily scores were recorded in 30 patients aged 0.7-17.5 years. Patients were studied at presentation and during treatment for acute lymphoblastic leukemia (ALL, n = 14; solid tumors receiving megatherapy with autologous bone marrow rescue (ABMR, n = 8), and chemotherapy for different tumors (miscellaneous, n = 8). The SS was compared with other nutritional parameters, including sequential anthropometric indices, serum albumin, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and whole-body protein turnover (WBPT) using [1-(13) C]leucine. The mean SS was reduced at diagnosis for all leukemic patients (median score = 8), improved during first remission (p < 0.002), fell to a minimum during febrile neutropenia (p = 0.0009), and improved with clinical and hematological recovery (p = 0.0009). A reduction in SS was related to fever (p < 0.001) and a fall in neutrophil count (p < 0.001). There was no correlation with anthropometric indices or IGF-I and IGFBP-3 levels. Paired WBPT studies in 9 patients showed that SS correlated well with protein breakdown (p = 0.026). The results suggest that the ongoing nutritional status of children with malignancy undergoing chemotherapy is best assessed using simple clinical parameters.
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PMID:Ongoing assessment of nutritional status in children with malignant disease. 978 5

The role of G-CSF, GM-CSF and M-CSF in the treatment of AML and ALL was reviewed. These CSFs significantly accelerate the neutrophil recovery after intensive chemotherapy, and reduce febrile neutropenia and documented infections. There is no clear evidence that CSFs accelerate early regrowth of AML cells at the doses and schedules presently used clinically except one study. Patients who have received CSFs tend to have a higher CR rate, which does not seem to be translated into definite survival benefit. There has been no prospective randomized study showing any beneficial priming effect of CSFs on AML cells with better clinical outcomes.
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PMID:Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor in the treatment of acute myeloid leukemia and acute lymphoblastic leukemia. 992 78


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