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)

Combination chemotherapy with cytosine arabinoside, cyclophosphamide and L-asparaginase (Asnase) was given to 22 children with acute lymphocytic leukaemia (ALL) with a white-cell count greater than 30 X 10(9)/1, and other features suggestive of poor prognosis. Complete remission was induced in all patients--in 19 after 2 courses of chemotherapy and in the remainder after a third course. During induction, neutropenia occurred in 18 and severe infection in 3. Anaphylaxis to Asnase occurred in 8 patients after the second course and one other had transient Asnase-induced diabetes. All patients received central-nervous-system prophylaxis after achieving remission, during which they were also treated with weekly vincristine and a 2-week course of prednisolone. Continuation therapy consisted of short cycles of intermittent chemotherapy and BCG inoculation or long cycles of intermittent chemotherapy +/- BCG. Life-table analysis shows 46% complete remission rate at 28 months, with 6 patients all in complete remission followed up between 28 and 41 months. There were minimal complications of continuation therapy, and BCG inoculation was well tolerated.
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PMID:Treatment of childhood lymphocytic leukaemia with high white-cell counts. 72 50

Short courses of cytosine arabinoside (Ara-C), cyclophosphamide, and L-asparaginase were given to seven children with newly diagnosed acute lymphocytic leukemia, who had failed to remit on standard remission induction therapy. These 4-day courses of Ara-C and cyclophophamide followed by 4 days of L-asparaginase were repeated at 3- to 4-week intervals for two or four courses. Complete remission occurred in six patients. The median duration of remission was 94+ days, on various maintenance regimens. The most serious side effect was neutropenia. This combination of these three drugs appears to be effective remission-induction therapy for children with ALL with unfavorable prognostic features.
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PMID:Combination chemotherapy for children with acute lymphocytic leukemia who fail to respond to standard remission-induction therapy. 105 44

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.
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PMID:Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). 241 66

From July 1984 to September 1987, 737 patients with aggressive malignant lymphoma (ML) were treated by an intensive regimen (LNH-84) comprising three or four courses of doxorubicin, 75 mg/m2; cyclophosphamide, 1,200 mg/m2; vindesine, 2 mg/m2 x 2; bleomycin, 10 mg x 2; and prednisolone, 60 mg/m2 x 5 (ACVB), consolidation with high-dose methotrexate, ifosfamide, etoposide, asparaginase, and cytarabine, and a randomized late intensification with two courses of cytarabine, cyclophosphamide, teniposide, bleomycin, and prednisone (AraCVmB). Four hundred forty-two patients had intermediate-grade ML, 221 highgrade ML, and 74 unclassified ML. Most of the patients had advanced disease: stage IIE (23%), III (13%), or IV (47%); 38% disseminated nodes; 38% two or more extranodal sites; and 41% a tumoral mass greater than 10 cm. Five hundred fifty-three patients (75%) went into complete remission (CR), 63 (9%) into partial remission, 62 (8%) failed to respond, and 59 (8%) died during ACVB courses, 17 of them from progression of the disease. With a median follow-up of 23 months, the estimated 2-year overall survival time to failure (TTF), and time to relapse (TTR) survival are 67%, 56%, and 67%, respectively. Patients receiving a late intensification had the same relapse rate as the other patients. A persistent fibronecrotic mass was found in 150 patients (20%) and did not influence the relapse rate. Toxicity was mainly neutropenia and infection during the ACVB courses, with 40 patients (5%) dying from septic complications while responding to treatment. Fifty-three percent of the patients had a neutropenia less than 0.500 x 10(9)/L, 58% fever (6% grade 4), and 49% a documented infection (8% grade 4). These results obtained with the LNH-84 regimen demonstrate that this therapeutic scheme is an effective treatment for aggressive ML.
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PMID:LNH-84 regimen: a multicenter study of intensive chemotherapy in 737 patients with aggressive malignant lymphoma. 247 57

Thirty-four children after multiple relapse or with refractory acute lymphoblastic leukemia were treated with two novel combinations of high-dose cytosine arabinoside, methotrexate, asparaginase, vincristine, and prednisone. The first combination was given to 19 patients. Oncolytic response and marrow hypoplasia was achieved in all. There were four early infectious deaths. Thirteen of the remaining 15 (87%) in whom the response to therapy could be evaluated achieved complete remission. Two achieved good partial remissions. The median duration of complete remission and survival on study was 8 and 10 months, respectively. The four proven and three suspected fungal infections seen in the initial 19 patients was the major toxicity observed. The therapy was modified in the last 15 patients to retain efficacy while reducing the period of neutropenia from a median of 28 to 22 days. No deep-seated fungal infections were seen in these patients. Twelve (80%) achieved a complete remission. Three had an oncolytic response without achieving remission. Eighty-three percent of the 30 evaluable patients, or 74% of all patients entered on study, achieved remission. It is anticipated that the therapy described here will not only achieve another remission in the majority of patients with advanced ALL but that the patients will be able to proceed to alternate therapies with potentially more durable benefit.
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PMID:Reinduction therapy for advanced or refractory acute lymphoblastic leukemia of childhood. 264 73

One hundred seventy-seven children with acute lymphoblastic leukemia (ALL) were admitted to a study designed to determine whether pulses of cytosine arabinoside (ara-C) and cyclophosphamide (cyclo) would improve disease-free survival (DFS). All patients received vincristine, prednisone, and asparaginase for remission induction, CNS prophylaxis with cranial irradiation and intrathecal methotrexate, and continuation therapy with 6-mercaptopurine plus methotrexate. Forty-seven of 101 patients with non-T ALL and 18 of 26 patients with T-cell ALL received ara-C/cyclo pulses every eight weeks during continuation therapy. The age, sex, and initial white cell count distributions were similar in both treatment groups. Patients with non-T-cell ALL had similar DFS with or without ara-C/cyclo pulses (36% versus 48%; P = 0.32). Ara-C/cyclo pulses significantly improved DFS in children with T-cell ALL (36% versus 0%; P = 0.015). Toxicities of the ara-C/cyclo pulses included reversible pancytopenia, drug induced fever, fever associated with neutropenia, and death in one patient from systemic candidiasis while neutropenic. This is the first clinical evidence to indicate that the combination of ara-C/cyclo used during continuation therapy is selectively beneficial in T-cell ALL.
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PMID:Cytosine arabinoside/cyclophosphamide pulses during continuation therapy for childhood acute lymphoblastic leukemia. Potential selective effect in T-cell leukemia. 349 11

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.
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PMID:Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia. 881 79

Because of the recommendation to avoid the concomitant administration of growth factors and chemotherapy, there is only limited information on colony-stimulating factor (CSF) therapy in acute lymphoblastic leukemia (ALL) induction protocols, in which cytotoxic drugs are administered in divided doses over a prolonged period of time, thus requiring a simultaneous administration of growth factors and chemotherapy. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF; filgrastim) as an adjunct to phase I of induction chemotherapy for adult ALL. Patients (n = 53) were randomized to receive no growth factor or G-CSF (5 microg/kg/d subcutaneously) starting on day 2 of chemotherapy consisting of daunorubicin (45 mg/m2) and vincristine (1.5 mg/m2) on days 1, 8, 15, and 22; L-asparaginase (2500 U/m2) on days 1 through 14; and prednisone (60 mg/m2) on days 1 through 28. A total of 25 patients in the G-CSF group and 26 patients in the control arm fulfilled the inclusion criteria of the study. G-CSF markedly ameliorated neutropenia because the median proportion of days with neutropenia less than 1,000/microL was 29% in the G-CSF group as compared with 84% in the control arm (P < .00005). The median time to reach absolute neutrophil counts (ANC) > or = 1,000/microL was 16 days in G-CSF patients and 26 days in controls (P < .001). More importantly, G-CSF significantly reduced the incidence of febrile neutropenia (12% v 42% in controls, P < .05) and documented infections (40% v 77%, P < .05). No significant differences were found with regard to requirements for red blood cell transfusions and platelet concentrates. A total of 24 of 25 (96%) patients in the G-CSF group and 20 of 25 (80%) evaluable control patients had complete remission after phase I of induction therapy. We conclude that G-CSF can be safely administered as an adjunct to induction therapy of ALL and is clinically beneficial by ameliorating neutropenia and reducing infectious complications.
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PMID:Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia--a randomized phase-III study. 922 58

An early intensive anthracycline therapy can improve therapeutic outcome in adult acute lymphoblastic leukaemia (ALL) but is usually associated with marked myelosuppressive effects and significant morbidity by infections. To reduce this risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5 microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study endpoints included time to recovery from neutropenic nadir, duration of neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of variables affecting G-CSF response, clinical outcome and costs. Sixty-five consecutive cases were evaluable. Patients in early G-CSF group recovered significantly faster from the neutropenic nadir (p < 0.002), contracted less infectious complications (p = 0.007), and required less intravenous antibiotic (p = 0.008) and antifungal (p = 0.002) medications. Although these reductions did not compensate for the increased G-CSF treatment cost, the overall supportive care cost was not significantly increased by early G-CSF. Interestingly, T-ALL phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were associated with a shorter neutropenic course even with late G-CSF. Early G-CSF may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and other similarly myelosuppressive adult ALL regimens.
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PMID:Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: effects, role of patient pretreatment characteristics, and costs. 925 Aug

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


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