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)

The complication of secondary myelodysplastic syndrome (sMDS) during the course of multiple myeloma (MM) has been recognized for more than a decade. sMDS occurs years after MM diagnosis, and typically, at sMDS presentation the MM is stable or inactive. We report a 56-year-old patient, who developed sMDS 15 years following the diagnosis of IgG-lambda MM, which had been completely stable for 13 years. However, very soon after sMDS was diagnosed, the MM relapsed and required combination chemotherapy. The first cycle of vincristine, adriamycin and dexamethasone (VAD) resulted in severe neutropenia and sepsis, which was treated with antibiotics and recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Two weeks after GM-CSF administration a transformation to acute myeloblastic leukemia was observed. The relation between GM-CSF and the leukemic transformation is discussed and the possible contribution of the cytokine to the stimulation of this complication is emphasized.
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PMID:Is granulocyte-macrophage colony-stimulating factor (GM-CSF) safe in myelodysplastic syndromes? 789 Feb 61

One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM-CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2-microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P < .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.
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PMID:High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. 791 45

Drug-related neutropenia is a common observation in AIDS patients. Haematological growth factors are therefore increasingly used in combination with myelotoxic agents to reduce the risk of infection and to improve the haematological tolerance of these regimens. We report a case of an AIDS patient with Kaposi's sarcoma who received GM-CSF for severe neutropenia due to anti-tumour chemotherapy combining alpha-interferon 2b and zidovudine. During GM-CSF administration there was a marked increase in the size of the Kaposi's sarcoma lesions as confirmed by ultrasonographic examination. As GM-CSF in vitro has been shown to promote Kaposi's sarcoma-like cell cultures, we discuss the potential role of this growth factor in increasing Kaposi's sarcoma lesions in vivo.
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PMID:Possible role of granulocyte-macrophage colony stimulating factor (GM-CSF) on the rapid progression of AIDS-related Kaposi's sarcoma lesions in vivo. 794 90

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.
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PMID:A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma. 795 Sep 23

To determine if ganciclovir given three times per week post-transplant is tolerable and effective for prevention of cytomegalovirus (CMV) infection in recipients of T cell-depleted marrow from related or unrelated donors, we have used ganciclovir 2.5 mg/kg iv three times daily on days -8 to -2 and 5 or 6 mg/kg iv 3 times per week from engraftment to day 100 as CMV prophylaxis for 51 adults who were CMV-seropositive or had seropositive donors. All patients received iv immunoglobulin 500 mg/kg weekly and CMV-negative or filtered blood products. Blood and urine were tested for CMV at weekly intervals through day 100. All patients received ganciclovir pre-transplant. Ten patients did not receive ganciclovir post-transplant (5 deaths, 3 graft failure, 1 renal failure, 1 required foscarnet). The median time to initiation of ganciclovir was 27 days (range 17-59 days) and the median duration of therapy was 51 days (range 5-83 range). Twelve patients had dose reductions (3 neutropenia and 9 renal insufficiency). Seven patients died before day 100, 2 had indications to change to foscarnet, 15 discontinued ganciclovir because of neutropenia and 17 completed the full ganciclovir course through day 100. G- or GM-CSF was given to 29 patients with neutrophils < 1.5 x 10(9)/l (10 had neutrophils < 0.5 x 10(9)/l) but only 12 of them could continue full-dose ganciclovir. Bacteremia occurred in 12 of the neutropenic patients. At day 120, the actuarial rate of CMV infection was 58% (95% CI 42-74%) and that of CMV disease was 36% (95% CI 21-51%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ganciclovir three times per week is not adequate to prevent cytomegalovirus reactivation after T cell-depleted marrow transplantation. 801 72

15 children with ALL and chemotherapy related neutropenia were treated with GM-CSF (Leucomax-Sandoz/Schering-Plough) in a dose of 5 micrograms/kg b.w./day during 7-10 days. Altogether 21 cycles were performed. Increase in the number of neutrophils in the majority of cases was observed already after 3 days of GM-CSF administration. The median time of neutropenia recovery was shorter in children treated with GM-CSF than in the control group. The frequency of severe infections was also significantly lower. No serous side effects were observed.
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PMID:[Use of rHu GM-CSF (Leucomax) in treatment of neutropenia during intensive chemotherapy for acute lymphoblastic leukemia]. 806 82

The results of clinical trials suggest that human hematopoietic factors are very usefull in overcoming neutropenia. Particularly, the great clinical benefit after G-CSF, GM-CSF therapy is observed in different types of neutropenia (cyclic, chronic neutropenia) aplastic anaemia, and neutropenias in infection diseases. At present, in acquired immunodeficiency syndrome, GM-CSF and other CSFs are envisioned in a primarily adjunctive role, supporting blood counts during period of myelosuppressive drug therapy.
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PMID:[Use of hematopoietic growth factors in nonmalignant neutropenias in adults]. 806 1

We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.
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PMID:Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases. 809 25

High-dose chemotherapy regimens can cure a number of otherwise incurable diseases, such as Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, acute leukemia (in remission), and breast cancer. Trials of high-dose chemotherapy have generally used autologous bone marrow transplant or peripheral blood stem cell support to ensure hematologic recovery after intensive chemotherapy and/or radiation. This report describes an approach in which high-dose carboplatin chemotherapy was followed initially by granulocyte-macrophage colony-stimulating factor (GM-CSF; Escherichia coli. Sandoz-Schering, East Hanover and Kenilworth, NJ) and in subsequent patients, by both GM-CSF and repeated cycles of peripheral blood progenitor cell (PBPC) collection and administration. The addition of PBPC to this regimen led to significant reductions in the duration of neutropenia and thrombocytopenia, the requirement for erythrocyte and platelet transfusions, the length of hospital stay, and the use of intravenous antibiotics in this group relative to those patients who received GM-CSF alone. In addition, laboratory studies are presented that show a direct correlation between the number of progenitor cells reinfused and the duration of neutropenia and thrombocytopenia. The report also reviews data indicating that circulating progenitor cells are depleted by this approach. This suggests that the number of progenitor cells available for mobilization is finite. Finally, the magnitude of these effects, and their implications for future trials with repetitive cycles of dose-intensive therapy, are discussed.
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PMID:High-dose carboplatin chemotherapy with GM-CSF and peripheral blood progenitor cell support: a model for delivering repeated cycles of dose-intensive therapy. 810 54

A 53-year-old man underwent chemotherapy (CDDP, VDS, MMC) for treatment of lung cancer. He was given 125 micrograms/m2 of GM-CSF subcutaneously every day for 8 consecutive days, in order to prevent neutropenia. Three days after starting GM-CSF therapy, marked eosinophilia in peripheral blood was observed. The maximum eosinophil count was 89% of leukocytes. Nine days after stopping the treatment with GM-CSF, the number of eosinophils had normalized spontaneously. There were no clinical symptoms except for slight fever, up to 37.5 degrees C. Moreover, there was no relationship between the number of eosinophils and the serum levels of cytokines (IL-3, IL-5, GM-CSF), although we observed minimal but significant elevation of serum ECP level. This case indicates that GM-CSF may induce marked eosinophilia rather than widely stimulating granulocytes and monocytes.
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PMID:[A case of marked eosinophilia in peripheral blood induced by rhGM-CSF]. 812 Oct 93


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