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)

Thirty patients with refractory or relapsed non-Hodgkin's lymphoma were treated with behenoyl ara-C (BH-AC) and nitrosoureas. Sixteen patients (53%) had a diffuse, large cell lymphoma and 22 patients (73%) had a stage IV disease. BH-AC, 250 mg/body, in combination with ACNU or MCNU, 50 mg/body, was administered by drip infusion for two days (Day 1, 2) every 3 to 4 weeks. Six patients (20%), all of them relapsed cases of diffuse lymphoma, obtained complete remission lasting one to six (mean: 2.5) months and 15 patients (50%) obtained partial remission lasting one to five (mean: 2.7) months. The major side effect was thrombocytopenia, and nine patients (30%) had required platelet-transfusions. There was no case complicated by infection due to prolonged neutropenia. Therefore, we conclude that BH-AC.Nitrosourea-therapy is very useful for the salvage chemotherapy of malignant lymphoma.
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PMID:[BH-AC.nitrosourea-therapy for refractory or relapsed malignant lymphoma]. 160 62

To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. 187 86

We have previously shown that the stem cell inhibitory peptide pGlu-Glu-Asp-Cys-Lys (pEEDCK monomer) leads to a good tolerance of otherwise lethal multiple ara-C doses and an increased survival of ara-C + peptide treated mice. This effect was due to the prevention of drug-induced CFU-S proliferation, thus keeping stem cells in a quiescent state insensitive to ara-C. Here we show that the pEEDCK monomer also inhibits stem cell proliferation after clinically relevant (non-lethal) ara-C doses. This leads to a sustained (100%) stem cell number in the femoral bone marrow, which was greatly reduced without protective peptide treatment (27%). We have measured the kinetics of influx of CFU-S into the empty S-phase (after two consecutive ara-C injections). This influx reached peak levels of 60-70%; pEEDCK treatment reduced it to 25-30%. Due to its cysteine content the pEEDCK monomer is easily oxidized and forms a symmetric disulfide-bonded dimer (pEEDCK)2. This dimer is a potent stimulator of haemopoiesis. Various modes of protective peptide treatment (monomer and dimer) were investigated in conjunction with a standardized protocol of 2 x 300 mg/kg ara-C given 12 h apart. (a) ara-monomer-ara: The administration of pEEDCK-monomer 2 h before the second ara-C injection retarded the onset of neutropenia, shortened its duration and improved recovery after depression. The degree of short-term neutropenia was not changed. (b) ara-ara-HN2-dimer: Post chemotherapy infusion of the stimulatory (pEEDCK)2 dimer led to considerable increases of progenitor levels (6.8 CFU-GM/1000 bone marrow cells vs. 1.2 CFU-GM/1000 in normal mice) 2 days after cytostatic treatment when CFU-GM were not detectable in unprotected mice. This increase was followed by greatly elevated granulocyte counts (8000 PMN/mm3 vs. 750 PMN/mm3 in normal mice). In the dimer-treated mice, up to 75% of the peripheral leukocytes were mature PMN (normal, 10%). (c) ara-monomer-ara-dimer: ara-C and monomer treatment as above (a) followed by dimer infusion led to complete protection of haemopoiesis. Mice treated with the protective pEEDCK monomer plus stimulatory dimer did not develop the leukocyte depression seen in unprotected animals. Our results show that the haemoregulatory peptide monomer and dimer can be used to improve the haematological status of mice treated with clinically relevant doses of cytostatic drugs (anti-metabolite and alkylating, alone and in combination). The pEEDCK monomer and dimer are equally active also on human haemopoietic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The use of haemoregulatory peptides (pEEDCK monomer and dimer) for reduction of cytostatic drug induced haemopoietic damage. 227 50

Cytosine arabinoside (ara-C) is an S-phase active antineoplastic agent used in the treatment of several hematologic malignancies. We did a retrospective analysis on 48 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) who were treated with high-dose ara-C between 1982 and 1987. All patients received between 9 and 24 g/m2/course of treatment with 90% receiving 12g/m2/treatment. Fifteen patients (25%) achieved a complete or partial remission. Of these, five (10%) were complete responders. Long-term disease-free survival was maintained only in those responders who were consolidated with autologous bone marrow transplantation. Toxicity was primarily myelosuppression. Seventy-five percent of patients developed fever and neutropenia with an equivalent percent having severe thrombocytopenia sufficient to require platelet transfusion. Five patients (10%) had significant neurotoxicity. There were seven treatment-related deaths (15%). Patients in whom tumors contained a small cell component responded better than patients with purely large cell or undifferentiated lymphomas (50% versus 15%, P = 0.024). We conclude that high-dose ara-C given as 3g/m2 every 12 hours for four doses has a limited role when used as a single agent in the treatment of relapsed or refractory non-Hodgkin's lymphoma. However, there are subsets of patients who may respond favorably to this therapy.
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PMID:High-dose cytosine arabinoside in relapsed and refractory non-Hodgkin's lymphoma. Limited role as a single agent. 255 38

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

A 30-year-old woman was diagnosed as having an acute promyelocytic leukaemia in September 1981. Chemotherapeutic courses of daunomycin, ara-C, thioguanine and prednisolone were administered, resulting in a complete remission. A relapse occurred in January 1982, and chemotherapy did not lead to a second complete remission; neutropenia persisted with a marked left shift of the marrow granulopoiesis. Courses of chemotherapy were given throughout the study. In September 1982, marrow promyelocytes markedly increased, making up 51% of the nucleated cells. One month later the situation was unchanged, and 13-cis-retinoic acid (1 mg/kg) was administered by mouth. Gradually the marrow proportion of promyelocytes decreased to normal levels. The peripheral blood and marrow were still normal after 20 weeks of treatment with retinoic acid. Thus, retinoic acid seemed to have been inducing differentiation in an abnormally increased, maturation-deficient population of promyelocytes in a patient with acute promyelocytic leukaemia.
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PMID:Probable in vivo induction of differentiation by retinoic acid of promyelocytes in acute promyelocytic leukaemia. 658 10

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5 micrograms/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (< 0.5 x 10(9)/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
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PMID:Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. A pilot study. 769 82

We report a case of sepsis due to Trichosporon cutaneum in a 20-year-old patient with acute promyelocytic leukemia. Neutropenia with a hypocellular marrow persisted for 90 days after two courses of induction chemotherapy with mitoxantrone and ara-C. Amphotericin B, fluconazole, and granulocyte-macrophage colony-stimulating factors were administered. Neutropenia (ANC < 1,000/microL) resolved 14 days after HLA-identical bone marrow transplantation. The patient is in remission, with a performance status of 100%, more than 1 year after transplantation.
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PMID:Long-term survival after allogeneic bone marrow transplantation complicated by trichosporosis. 811 5

A total of 16 patients with refractory leukemia have been entered on a phase I study employing escalating doses of a 96 h continuous infusion of high-dose cytosine arabinoside (ara-C) administered in conjunction with a 120 h infusion of a fixed dose (22 g/m2 per day) of 2'-deoxycytidine (IND 28108) as a host-protective agent. Extramedullary toxicities, even at the highest ara-C dose level (e.g. 14 g/m2 per day) were mild (e.g. CALGB grade I or II), and consisted of diarrhea, fluid retention, somnolence, hepatic dysfunction, and febrile episodes. Neutropenia and thrombocytopenia were noted in all patients, but no serious infections or bleeding episodes were encountered. Steady state plasma ara-C concentrations of 20-60 microM were observed in patients treated at the 14 g/m2 dose, and were associated with plasma ara-U concentrations approaching 1 mM. Although no complete remissions were obtained at the ara-C dose levels tested to date, three partial remissions were noted, and the large majority of patients experienced a clearing of peripheral blood blasts. In addition, several patients who failed to achieve objective responses exhibited atypically benign clinical courses following completion of therapy. These findings demonstrate that 2'-deoxycytidine protects humans from otherwise lethal doses of high-dose ara-C administered by continuous infusion, and substantially ameliorates the hematologic and non-hematologic toxicity of such regimens without completely abrogating antileukemic activity. Determination of the ultimate efficacy of this strategy will require identification of an ara-C maximum tolerated dose and evaluation of the antileukemic potential of this regimen in prospective phase 11 trials.
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PMID:Phase I study of a continuous infusion of high-dose ara-C in conjunction with a fixed dose of 2'-deoxycytidine (IND 28108) in patients with refractory leukemia: an interim report. 825 91

The hemoregulatory peptide, pGlu-Glu-Asp-Cys-Lys (pEEDCK or HP5b), has been shown to reversibly inhibit the proliferation of bone-marrow progenitor cells, and has been reported to protect mice from the myelotoxicity associated with ara-C, a chemotherapeutic agent. We undertook to use this reagent to reduce radioimmunotherapy(RAIT)-associated bone-marrow toxicity by suppressing hematopoiesis during the critical period when bone marrow is exposed to radiation. The reported studies optimize the use of HP5b to reduce the duration of neutropenia and thrombocytopenia. We found that 3.6 micrograms/day of HP5b administered through a continuous 7d mini-osmotic pump, together with a bolus dose of 3.6 micrograms 3 hours before the radioantibody dose, gave the best effect, as measured by neutrophil counts on day 28 post RAIT. With sub-lethal doses of RAIT, the period of neutropenia was reduced by 2 weeks, and there appeared to be more rapid recovery of morphologically mature myeloid cells. The peptide, however, does not appear to alleviate the lymphotoxicity associated with RAIT. No adverse effects have been noted from continuous infusions of the peptide. In the past, we reported that cytokines (IL-I/GM-CSF) are not marrow-restorative when given after RAIT. However, an additive effect is observed when HP5b infusions are combined with post-RAIT cytokine administration, suggesting that a significant pool of bone-marrow progenitor cells remains when HP5b is co-administered with RAIT. Thus, HP5b is an alternate approach to reducing myelotoxicity, and may be used in combination with cytokines to further reduce the duration of myelosuppression.
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PMID:Reduction in the duration of myelotoxicity associated with radioimmunotherapy with infusions of the hemoregulatory peptide, HP5b in mice. 903 35


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