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)

Twenty three patients with relapsing (n = 11) or refractory (n = 12) non-Hodgkin's lymphoma (NHL) to one or two prior anthracycline based combination chemotherapy regimens were treated as second or third line regimen with 3 induction cycles of Idarubicin (IDA) (7 mg/m2/d i.v. d1-d3) and high dose cytarabine (HD Ara-C) (1 g/m2/12 h i.v. d1-d3), each cycle was repeated every 3 weeks. Responding patients received a maintenance therapy with monthly cycles of IDA: 15 mg/m2 d1-d3, Etoposide 100 mg/m2 d1-d3, both by oral route. Twenty two patients are evaluable and we observed 13 CR and 1 PR with an overall response rate of 61% (14/23: 95% Cl = 38.5% 80.3%). The median time to progression was 32 months (6.5 - 63 + m.). The response rate to IDA-HD Ara C was not different for patients with (n = 14) or without (n = 9) objective response to the last prior therapy. The main toxicity was hematological: all patients experienced grade 4 neutropenia and 22 patients had grade 4 thrombopenia, but there were no toxic deaths. IDA and HD-Ara-C combination is highly effective in refractory or relapsed. NHL. As hematological toxicity was the limiting factor for further escalation of dose-intensity, further studies might include hematopoietic growth factors support in the therapeutic scheme.
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PMID:Idarubicin and high dose cytarabine: a new salvage treatment for refractory or relapsing non-Hodgkin's lymphoma. 881 82

Twenty-two patients with refractory or relapsed AML were treated with FLAG [25 mg/m2 fludarabine daily (days 1-5), 2 g/m2 daily Ara-C (days 1-5) and 400 micrograms/m2 daily G-CSF (day -1 till the absolute neutrophil count was > 500/microliter)]. Median age was 46 years (range 24-63). Eight patients had leukemia which was primarily refractory to conventional regimens, six were in first, seven were in second, and one was in third relapse. Overall, 11 of 22 (50%) patients achieved complete remission (CR), three had a partial response (PR), and seven did not respond (NR). One patient died of an early cerebral hemorrhage. The median remission duration from achievement of CR after FLAG was 9.9 months and median survival was 13.0 months. One patient is alive in CR at 31.9 months. Hematological toxicity of the regimen was severe. The median time to neutrophil recovery (ANC > 500/microliter) was 21 days (range 18-33). A median of seven red cell units (range 0-22) and of six platelet concentrate units (range 3-28) had to be given. Median duration of febrile neutropenia was 2 days (range 0-20 days) and patients were on i.v. antibiotics for a median of 16 days (range 0-51). There was no death from infection. Nonhematological toxicity was remarkably low, with almost no neurotoxicity and no major hepatotoxicity. In conclusion, FLAG seems to be an efficient and well tolerated regimen. It may be particularly useful for patients who have a sibling or unrelated donor for subsequent allogeneic bone marrow transplantation.
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PMID:FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute myeloid leukemia. 900 55

This is a retrospective study on the use of cytarabine at low doses in acute myeloid leukemias in 41 patients. Four groups of AML are included: group A: 19 cases of de novo AML in elderly patients; group B: ten cases of AML in relapse; group C: five cases of AML refractory to previous treatment and group D: seven cases of secondary AML. Cytarabine was given subcutaneously at the dose of 10 mg/m2 of body surface, for 21 days per month for the first course; then 15 days per month for the following courses. The response rates were 42, 20, 0, and 43% respectively for the A, B, C, and D groups. A complete remission was attained in only 15% (six patients). Extra haematological tolerance was excellent. Infection complications were noted in 66%, whereas a severe neutropenia was observed in 34% of patients. Hemorrhagic complications were more rare (20% of patients). The mean duration of complete remission was 10 months. The median survival was 10.5 months (2 to 31 months) for the responder patients, and 2.4 months (1 to 7 months) for the non-responders. Cytarabine at low doses seems to be a good indication for first intention treatment of AML in elderly patients. It does not give a bone marrow aplasia, the infection and hemorrhagic episodes are less numerous than with conventional dose chemotherapy, the life quality is improved, and treatment at home is often possible.
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PMID:[Low dose cytarabine in the treatment of acute myeloid leukemia. Apropos of 41 cases]. 911 80

High-dose cytarabine alone or in combination with mitoxantrone has been shown to be active against refractory non-Hodgkin's lymphoma in therapeutic trials. We administered these two drugs to 16 patients with advanced and refractory non-Hodgkin's lymphoma. Cytarabine was administered at 3 g/m2 as a 2-h intravenous infusion every 12 h on days 1-4 (8 doses) and mitoxantrone at 6 mg/m2/day as a 1-h intravenous infusion on days 1-5. The clinical efficacy and toxicity were assessed according to the WHO criteria. Five patients (31%, 95% CI: 8-54%) attained complete remission and two had partial remission. In three of the five complete remission patients, the remission lasted for > 4 months. The remaining two patients had complete remission for only 1.3 months. Myelosuppression with subsequent infection was the major toxicity of this regimen. Severe leukopenia (WBC < 1000/microliter) lasted for an average of 20 days and thrombocytopenia (< 25000/microliter) 18 days. Five patients (31%) died of treatment-related complications: neutropenia-associated sepsis in three, pneumonia in one and electrolyte imbalance in one. Nonmyeloid toxicities included alopecia in 100% (19% Gr.2, 75% Gr.3), stomatitis in 88% (13% Gr.2, 31% Gr.3), hepatotoxicity in 38% (6% Gr.2, 6% Gr.3), dermatitis in 31% (19% Gr.2), CNS toxicity in 25% (6% Gr.2, 6% Gr.3), infection in 38% (13% Gr.3, 19% Gr.4) and chemical conjunctivitis in 6% (Gr.2). We conclude that a proportion of refractory non-Hodgkin's lymphoma cases will respond to high-dose cytarabine+mitoxantrone, but that the treatment seems too toxic to be acceptable as salvage therapy for refractory non-Hodgkin's lymphoma.
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PMID:High-dose cytarabine and mitoxantrone as salvage therapy for refractory non-Hodgkin's lymphoma. 925 69

We compared the use of low-dose G-CSF (50 microg/m2/day), following salvage chemotherapy, for mobilization of PBSC with the results obtained in a comparable historical control group who received a standard dose of G-CSF (5 microg/kg/day, approximately 200 microg/m2/day). Thirty adult patients with relapsed or refractory lymphoma were treated with ifosfamide, VP-16, intermediate-dose Ara-C, methylprednisolone (IAPVP-16) and G-CSF 5 microg/kg/day (group A, n = 15) or 50 microg/m2/day (group B, n = 15) from day 6 until the end of leukaphereses. The duration of neutropenia and thrombocytopenia were equal in both groups. A median of two (1-3) leukaphereses were performed in both groups to harvest >3.5 x 10(6)/kg CD34+ cells. The numbers of circulating CD34+ cells on the first day of leukocyte recovery were similar in both groups in those patients mobilized after a first cycle of IAPVP-16. The numbers of circulating CD34+ cells were similar in patients mobilized after a first and after a second IAPVP-16 in group A. In the low-dose group (group B), however, the numbers of circulating CD34+ cells were significantly lower in those mobilized after a second than after a first course. Additionally, the product of the first leukapheresis contained significantly fewer CD34+ cells in those mobilized after a second course only in group B, with no differences in group A. Nevertheless, the final products harvested did not differ in the content of MNC, CFU-GM and CD34+ cells, suggesting that these differences are not clinically important. These results indicate that the use of low-dose G-CSF (50 microg/m2/day) is as effective as 5 microg/kg/day in accelerating neutrophil recovery and mobilizing CD34+ cells after a first cycle of IAPVP-16 salvage chemotherapy, resulting in a substantial decrease in costs, while more heavily pretreated patients may require higher doses of G-CSF for an equivalent mobilization.
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PMID:Efficient peripheral blood stem cell mobilization with low-dose G-CSF (50 microg/m2) after salvage chemotherapy for lymphoma. 940 26

A retrospective study of hepatosplenic candidiasis in patients with acute leukemia from a single centre was performed. The significance of age, sex, type of leukemia, dose of cytosine arabinoside (Ara-C), duration of neutropenia, steroid use and period of therapeutic antibiotics in the development of hepatosplenic candidiasis was analyzed, using logistic regression analysis. Nine of 51 patients had hepatosplenic candidiasis. Ara-C use was highly associated with the development of hepatosplenic candidiasis (p = 0.001); with a high association with a higher dose (p < 0.0001). On the basis of these results consideration should be given to further trial of antifungal prophylaxis for patients receiving high dose Ara-C.
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PMID:High dose cytosine arabinoside is a major risk factor for the development of hepatosplenic candidiasis in patients with leukemia. 947 28

Older age is a poor prognosis factor in acute myeloid leukemia (AML). This double-blind trial was designed to test the hypothesis that granulocyte colony-stimulating factor (G-CSF) used as supportive care could improve the treatment of elderly AML patients. Two hundred thirty-four patients 55 or more years of age with a morphologic diagnosis of de novo or secondary AML, French-American-British (FAB) M0-M7, excluding M3, were randomly assigned to a standard induction regimen (daunorubicin at 45 mg/m2 intravenously [IV] on days 1 through 3 and Ara-C at 200 mg/m2 IV continuous infusion on days 1 through 7) plus either placebo or G-CSF (400 microg/m2 IV over 30 minutes once daily). Results are reported here for 211 centrally confirmed cases of non-M3 AML. The two groups were well balanced in demographic, clinical, and hematological parameters, with median ages of 68 years in the G-CSF and 67 years in the placebo groups. The complete response (CR) rate was not significantly better in the G-CSF group: 50% in the placebo and 41% in the G-CSF group (one-tailed P = .89). Median overall survival was also similar, 9 months (95% confidence interval [CI], 7 to 10 months) in the placebo and 6 months (95% CI, 3 to 8 months) in the G-CSF arms (P = .71). We found a significant 15% reduction in the time to neutrophil recovery in the G-CSF group (P = .014). G-CSF had no impact on recovery from thrombocytopenia (P = .80) or duration of first hospitalization (P = .27). When infection complications were evaluated, G-CSF had a beneficial effect on the duration but not on incidence of infection. G-CSF patients had fewer days with fever and shorter duration of antibiotic use. However, there was no difference in the frequency of total documented infections or in the number of fatal infections (19% placebo v 20% G-CSF). In this study of elderly AML patients, G-CSF improved clinical parameters of duration of neutropenia and antibiotic use, but did not change CR rate or survival or shorten hospitalization.
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PMID:A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). 957 95

A 38-year-old woman who had been treated for refractory anemia was admitted with severe pancytopenia, persistent fever and splenomegaly in May 1995. The bone marrow biopsy revealed hyperplastic marrow with marked fibrosis. Shortly after admission, cardiac tamponade developed. Though low-dose Ara-C therapy successfully controlled the tamponade, no hematological recovery was obtained. Then a chemotherapy consisted of Ara-C, acrarubicin and M-CSF was done and the neutropenia was improved. However, progressive leukocytosis with monocytosis and splenomegaly subsequently developed. Thus, the disease was considered to progress to CMML. Localized pulmonary infiltrates associated with a cavity, a pulmonary artery aneurysm and a recurrent high fever developed in October 1995. Though invasive pulmonary aspergillosis was suspected, blood and sputa culture, as well as serological tests were negative. In February 1996, massive hemoptysis occurred and the patient died due to respiratory failure after an emergency right lobectomy of the lung. Pathological examination of the operated lung disclosed that the localized pulmonary infiltrates consisted of monocytoid cells. Infiltration of the monocytoid cells in the tissue surrounding the pulmonary aneurysm was also observed. However, no pathologic organisms were detected at all. Thus, the leukemic cells were considered to have infiltrated locally into the lung.
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PMID:[Localized pulmonary infiltration in chronic myelomonocytic leukemia]. 957 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

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.
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PMID:Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS. 972 93


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