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)

Chemotherapy-induced neutropenia is a major dose-limiting factor in the management of cancer patients. Most chemotherapeutic agents are active against proliferating cells, interfering with DNA replication and/or mitosis. A number of chemokines, notably macrophage inflammatory protein-1 alpha [MIP-1alpha], have been reported to induce cell-cycle arrest in immature hematopoietic progenitors, raising the possibility that chemokines, such as MIP-1alpha, could be used to reduce or even eliminate the hematologic toxicity of cycle-active chemotherapy. We tested the effectiveness of BB-10010 [a genetically engineered analog of human MIP-1alpha] in vivo against three different cytotoxic drugs [cyclophosphamide (Cy), 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C)] commonly used in cancer therapy. BB-10010 treatment reduced the toxicity of all three agents, though the precise mode of protection varied with the cytotoxic drug used. BB-10010 reduced the neutropenic interval in Cy-treated mice without affecting the neutropenic nadir, whereas the absolute neutrophil counts [ANC] of both 5-FU and Ara-C treated mice were significantly higher throughout the neutropenic interval for mice receiving BB-10010 prior to chemotherapy. These findings indicate that the ability to manipulate the cell cycle of hematopoietic progenitors with chemokines, such as BB-10010/MIP-1alpha and other negative regulators, may be exploited to reduce chemotherapy-induced neutropenia; furthermore, the fact that BB-10010 is effective against several different cytotoxic agents is cause for guarded optimism that this approach may be generally applicable, and, once optimized for patient use, may prove to be of significant clinical benefit.
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PMID:Protective effects of BB-10010 treatment on chemotherapy-induced neutropenia in mice. 1002 56

Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) postinduction. Modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC >50000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186000/mm3 and 200000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs. non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs. the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs. 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.
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PMID:Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report. 1072 Jan 28

A 43-year-old female with a peripheral white cell count of 118.0 x 10(9)/L and 96% blasts was diagnosed with acute myeloid leukemia (AML), FAB M4. Cytogenetics, performed on a bone marrow sample, revealed the following abnormal karyotype: 46,XX,ins(16)(q22p13.1p13. 3). Fluorescence in situ hybridization (FISH) confirmed the inter-arm insertion using a probe for 16p. The result of this structural rearrangement was the fusion of CBF beta to MYH11 seen commonly in inv(16)(p13q22). The patient commenced high-dose intensive combination chemotherapy (big ICE; Idarubicin, Cytarabine, and Etopiside). Five days post chemotherapy, she developed febrile neutropenia. Despite broad spectrum intravenous antibiotics and antifungal therapy, the patient died at day nine post chemotherapy. This case demonstrates a previously unreported structural abnormality of chromosome 16 in a patient with AML M4, which represents a third mechanism to inv(16)(p13q22) and t(16;16)(p13q22) in producing the CBF beta-MYH11 fusion. CBF beta-MYH11 fusions masked by cryptic translocations at the cytogenetic level have been detected by FISH and PCR techniques. Due to the improved prognosis associated with CBF beta-MYH11 fusions compared to the standard risk group for AML, its detection remains important.
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PMID:A unique structural abnormality of chromosome 16 resulting in a CBF beta-MYH11 fusion transcript in a patient with acute myeloid leukemia, FAB M4. 1095 41

Gemcitabine is a cytosine arabinoside (Ara-C) analog with activity in many human tumor systems. We evaluated the drug's activity in resistant or relapsing multiple myeloma. Gemcitabine 1000 mg/m2 was administered as a 30 minute infusion on days 1, 8, and 15 of a 28-day cycle. No dose escalations were permitted and dose reductions were scheduled for hematologic toxicity. Twenty-nine eligible patients were entered into Southwest Oncology Group (SWOG)-9803. One patient received no treatment and 5 patients had inadequate response assessments. The major toxicity was hematologic with grade 3/4 neutropenia in 9 and grade 3/4 thrombocytopenia in 15 patients. No responses were seen. Stable disease was confirmed in sixteen patients (57%). Median survival was eight months. Gemcitabine as utilized in this trial has shown little activity and is not to be strongly considered for future multiple myeloma trials.
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PMID:The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase II: a Southwest Oncology Group study. 1200 87

A prospective study was conducted in 1999 at the National Cancer Institute, Cairo University, to estimate the incidence, morbidity and mortality of fungal infections along with the evaluation of risk factors influencing outcome of infections among paediatric cancer patients. Of 1917 infectious episodes, the fungal infection rate as documented both clinically and microbiologically was 3.7% (70 cases). Fungal pathogens isolated were yeasts in 55 patients (78.6%) and moulds in 15 patients (21.11%). Among yeasts, Candida parapsilosis was the commonest, followed by C. tropicalis. Pneumonia was the most common fungal infection (n = 25, 35.7%), followed by fungaemia (n = 18, 25.7%). The overall mortality rate was 40% (n = 28), with an infection-related mortality of 28.5% (n = 20). Risk factors that accompanied mortality were relapsing or recurrent disease, profound neutropenia, ADE (Ara-C, daunorubocin and etoposide) protocol of chemotherapy, C. tropicalis isolated and fungaemia as a site of infection. Early use of empirical antifungal therapy (day 4) was not associated with a better outcome. In the light of the poor outcome of patients with fungaemia and fungal pneumonia, every effort should be made to prevent these infections in paediatric cancer patients.
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PMID:A prospective study on fungal infection in children with cancer. 1213 78

We designed a phase I trial to assess the feasibility of the combination of topotecan, Ara-C, cisplatin and solumedrol (TOPOSHAP) in patients with relapsed or primary refractory lymphomas. We included 9 patients with measurable non-Hodgkin's (n = 8) and Hodgkin's (n = 1) lymphomas. Level 1 consisted of topotecan 1.0 mg/m(2)/day, i.v., given on days 1-3, cisplatin 25 mg/m(2)/day, i.v., on days 1-3, Ara-C 500 mg/m(2), i.v., on day 4, methylprednisolone 250 mg, i.v., on days 1-4. The regimen was repeated every 3-4 weeks. The maximum tolerated dose was already reached at level 1. G-CSF was added systematically after the 5th patient was included. The most significant toxicity in this trial was hematologic (all had neutropenia WHO grade 4 and 7 had grade 4 thrombocytopenia). Three patients had neutropenic fever. We observed two instances of WHO grade 3 and one of grade 4 diarrhea. Two patients achieved a complete response and 6 a partial response. We conclude that TOPOSHAP with G-CSF support is feasible and should be further studied in phase II studies.
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PMID:Topotecan, Ara-C, cisplatin and prednisolone (TOPOSHAP) for patients with refractory and relapsing lymphomas: results of a phase I trial. 1534 92

Treatment of acute myelogenous leukemia (AML) incorporates the use of growth factors towards several objectives, including abbreviating the time of neutropenia, reducing susceptibility to infections, reducing length of hospitalization, and increasing susceptibility of the blasts to chemotherapy drugs, or priming. Priming is defined as the driving of leukemia cells into cell cycle in order to increase response to S-phase-specific drugs such as cytarabine (Ara-C). Growth factors that have been used in priming include both filgrastim (G-CSF) and sagramostim (GM-CSF). Priming has often been applied in the treatment of older patients, who do not respond as well to standard treatment regimens, and whose disease was transformed from a myelodysplastic syndrome (MDS), or preleukemia. Recent, large randomized trials have demonstrated that although subgroups of patients may benefit, there does not appear to be any improvement in the complete remission rate sustained by inclusion of growth factor priming as part of the initial therapy of acute myelogenous leukemia.
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PMID:Growth factor priming in therapy of acute myelogenous leukemia. 1549 74

A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML). Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy. The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05). The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria.
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PMID:[Infection control in neutropenia induced by high-dose cytarabine chemotherapy]. 1557 Sep 30

The objective of this study was to examine the incidence and characteristics of Ara-C-related fever and the frequency and severity of infections after single-drug, high-dose Ara-C treatment (HDAC) in children treated for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). A retrospective review was performed of 169 courses of HDAC administered to 57 patients (age 1.8-17.8 years). Procalcitonin values (PCT) were analyzed in a subgroup of 16 patients. Fever during HDAC occurred in 113 of 169 (67%) cases. C-reactive protein (CRP) was elevated in the febrile patients (median 38 mg/L [range 3-150]). PCT was elevated (>0.5 ng/mL) during HDAC in 4 of the 16 evaluated patients. Corticosteroids could inhibit fever (P < 0.001). Myelosuppression after HDAC was prominent: 99% developed neutropenia (<0.5 x 10/L) and 92% thrombocytopenia (<25 x 10/L). An early lymphopenia (median 0.1 x 10/L [range 0.01-0.68]) was seen during the first week. G-CSF was used after 12 of the 169 HDAC courses. A febrile episode occurred after 93 of the 169 (55%) HDAC courses, with no need for intensive care and no deaths. The incidence of viridans streptococcal septicemia was 2 of the 169 cases. Ara-C fever is common, and evaluation with inflammation markers is complicated by the fact that HDAC can induce a moderate release of both CRP and PCT. Profound neutropenia and lymphopenia are causative factors for the high incidence of infections, but the risk of life-threatening complications after HDAC in children in remission of lymphoid malignancies is low, even without prophylactic use of colony-stimulating factors.
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PMID:Ara-C fever and infections after high-dose ara-C treatment in pediatric lymphoid malignancies. 1601 25

One hundred twelve patients with geriatric acute myeloid leukemia (AML), refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia with excess of blasts in transformation (MDS-RAEBt) were entered into this study to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in combination with granulocyte colony-stimulating factor [G-CSF]) with the objective of evaluating the efficacy and tolerance of this regimen. Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days 1 to 14. Aclarubicin was administered intravenously at a dosage of 14 mg/m2 per day on days 1 to 4 (CAG regimen A) or 7 mg/m2 on days 1 to 8 (CAG regimen B). Recombinant G-CSF was given subcutaneously at a dosage of 200 3g/m2 per day on days 1 to 14. We demonstrated comparable overall complete remission rates for the 4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5% (5/13) in the MDS-RAEBt patients. Of the 52 patients followed up, the 12-month progression-free survival (PFS) and overall survival (OS) rates estimated by the Kaplan-Meier method were 40.73% 3 8.15% and 42.85% 3 8.23%, respectively. The median PFS and OS times were 9.0 3 2.2 months and 11.0 3 1.6 months, respectively. Toxic effects were very rare and mainly consisted of neutropenia and thrombocytopenia due to myelosuppression; approximately 70% to 80% of patients had neutropenia or thrombocytopenia that exceeded National Cancer Institute grade II. Nonhematologic toxicities were not observed in this study. The CAG regimen seems promising, with acceptable toxicity, for the treatment of various categories of poor-prognosis AML and MDS-RAEBt.
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PMID:Aclarubicin and low-dose Cytosine arabinoside in combination with granulocyte colony-stimulating factor in treating acute myeloid leukemia patients with relapsed or refractory disease and myelodysplastic syndrome: a multicenter study of 112 Chinese patients. 1610 59


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