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)

Ten cases of newly diagnosed pediatric B cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia (B-NHL, stage I & II 6 cases, stage III & IV 2 cases/ALL 2 cases) experienced during the last 7 years (1987-1994) were treated by BLK88 protocol, which consisted of HD-CPM (1,200 mg/m2), and HD-MTX (1,000 mg/m2) with VCR, ADR, and/or AraC combination, and CNS prophylaxis by triple intrathecal injection. The therapy duration was 24 weeks for B-NHL (36 weeks for B-ALL). The results showed that while one of the six cases in stage I & II relapsed, and other 4 cases of stage III & IV B-NHL/ALL remained in complete remission. On the other hand, all of the four cases in stage III & IV in historical controls had relapsed. Neutropenia and liver dysfunction were observed during therapy, but they were tolerable. We conclude that BLK88 is a very useful protocol for B-NHL/ALL in childhood.
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PMID:[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol]. 884 99

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.
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PMID:High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group. 885 46

Cytokines are involved in hematopoiesis by regulating proliferation, differentiation and cellular functions of various lineages of hematopoietic cells. There is an increasing range of clinical conditions in which cytokines are involved as therapeutic agents. One of the most advanced and successful applications is the stimulation of hematopoiesis by the colony stimulating factors (GM-CSF and G-CSF) and erythropoietin. Hematopoietic growth factors are effective in accelerating recovery from neutropenia after chemotherapy and bone marrow transplantation and in reducing incidence of infections. Interferon alpha (IFN-alpha) proved a useful therapeutic agent for chronic myelogenous and hairy cell leukemias as well as for multiple myeloma and non-Hodgkin's lymphoma. Interleukin 2 is the only cytokine apart from IFN-alpha accepted as antineoplastic agent. It may be useful as adjuvant therapy in the hematological malignancies. It may be supposed that in the near future new recombinant cytokines will be introduced in the treatment of blood diseases.
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PMID:Cytokines in the treatment of hematological disorders: recent progress and perspectives. 887 63

Systemic non-Hodgkin's lymphoma and Kaposi's sarcoma occur in approximately 4% and 30% of patients with HIV infection, respectively. Single-agent or combination chemotherapy is often indicated for such patients. Combination chemotherapy produces a significant decrease in CD4 lymphocytes and significantly increases the risk of opportunistic infection. Supportive care should include prophylaxis against Pneumocystis carinii pneumonia and esophageal candidiasis. Herpes labialis frequently occurs, may be confused with chemotherapy-induced stomatitis, and it requires appropriate treatment and secondary prophylaxis once recognized. Antiretroviral therapy should be continued during chemotherapy, if possible, and should be selected based on the patient's prior antiretroviral exposure, the toxicity profile of the antiretroviral agent, the toxicity of the chemotherapy, and the potential for drug interaction. The use of hematopoietic growth factors as primary prophylaxis may be reasonable for patients at high risk for febrile neutropenia, although the information about their use in this population is limited.
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PMID:Infection prophylaxis and antiretroviral therapy in patients with HIV infection and malignancy. 891 6

In order to determine the incidence rate of oral lesions associated with chemotherapy, as well as well as its association with clinical and laboratory parameters and potential risk factors, 50 in-patients with non-Hodgkin's lymphoma or leukaemia under chemotherapy were followed from January 1993 to May 1994. Basal and weekly oral examinations were performed. Clinical and laboratory data were registered. Wilcoxon's rank sum test, chi square test, univariate and multivariate logistic regression analyses were used, 36 individuals with leukaemia and 14 with non-Hodgkin's lymphoma were followed for 158 weeks; mean age was 33 years (range 15-85). Oral lesion incidence rate was 45/100 patients-week. Exfoliative cheilitis and infections (herpes and candidosis) were the most common oral complications, followed by haemorrhagic lesions and mucositis. Haemorrhagic lesions correlated with thrombocytopenia (RR = 30.5). Etoposide administration (RR = 8.6), alkylating agents (RR = 15.6), a prior course of chemotherapy (RR = 23.2) and neutropenia (RR = 4.16) were predictors of mucositis. Oral lesions were a common complication in this study, and a possible association of mucositis with several factors is suggested.
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PMID:Chemotherapy-associated oral mucosal lesions in patients with leukaemia or lymphoma. 894 35

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
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PMID:Cytokine therapy for hematological malignancies. 899 Jun 22

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.
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PMID:Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy. 899 Jul 72

Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble derivative of etoposide, a semisynthetic podophyllotoxin that is important in the treatment of a variety of malignancies, including lung cancer, germ cell tumors, non-Hodgkin's lymphoma, Hodgkin's lymphoma, acute leukemia, etc. Because etoposide is poorly water soluble, it must be dissolved in a polysorbate 80-based solvent mixture, which is moderately allergenic and requires a large volume of saline for administration. Etoposide phosphate is water soluble and is rapidly converted in vivo to etoposide by endogenous phosphatases. Because it is water soluble, etoposide phosphate can be administered in volumes much smaller than those required with etoposide therapy, permitting rapid intravenous administration in the outpatient setting. We recently reported the results of a phase I study using etoposide phosphate on a bolus, daily x 5 schedule. Like others, we demonstrated that etoposide phosphate has pharmacokinetic properties virtually identical to those of etoposide. Our dose-finding study indicated that etoposide phosphate can be used in doses up to 100 mg/m2/d x 5 every 3 weeks in patients who have not had extensive prior chemotherapy, and that a dose of 75 mg/m2 would be appropriate for patients who had undergone multiple prior therapies or who had prior radiotherapy. The dose-limiting toxicity was neutropenia. Paclitaxel, a microtubule-stabilizing agent, is active against a variety of solid and hematopoietic malignancies that overlap with those against which etoposide is active. Because the mechanisms of action of these two agents differ, it is logical to suppose that the combination of the two agents might produce some additive effect when used to treat cancers that respond to both individual agents. We therefore undertook a phase I study using paclitaxel as a 3-hour infusion in combination with a 5-minute infusion of etoposide phosphate daily x 3 every 21 days. We used the 3-hour paclitaxel schedule because it has been shown to be less myelotoxic than longer infusions at the same doses. Our goal in this ongoing study is to determine the maximum tolerated doses of the two drugs in combination, to determine the toxicities of the regimen, and to assess its anticancer activity.
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PMID:A phase I study of etoposide phosphate plus paclitaxel. 899 73

Irinotecan hydrochloride (CPT-11) is a new derivative of camptothecin which inhibits topoisomerase I. Phase II studies have demonstrated that CPT-11 is active against a broad spectrum of neoplasms including intractable non-Hodgkin's lymphoma. An early phase II study in lymphoma suggested that a schedule of daily infusions of 40 mg/m2/day for three or five consecutive days is more effective than a single infusion of 200 mg/m2 every three to four weeks. Carboplatin is also an active agent against lymphoma, and preclinical studies have shown that CPT-11 and its active metabolite have a synergistic effect with platinum compounds. To evaluate the maximal tolerated dose (MTD) and the therapeutic efficacy of CPT-11 in combination with carboplatin in relapsed or refractory non-Hodgkin's lymphoma, we conducted a combination phase I/II study. The starting dose of CPT-11 was 20 mg/m2/day (days 1 through 3 and 8 through 10), and dose escalations of 5 mg/m2/day increments were planned, with a fixed dose of carboplatin (300 mg/m2, day 1). Six of the eight patients receiving both agents at the starting dose level developed critical toxicities such as grade 4 hematologic (neutropenia 6/8, thrombocytopenia 1/8) and grade 3 non-hematologic toxicities (diarrhea 2/8, transaminase elevation 1/8). Further dose escalation of CPT-11 was halted, and the starting doses were judged to be the MTDs. The response rate (25%, 2/8) to the combination of the MTDs was not superior to that of CPT-11 alone in a previous phase II study (38%, 26/69), and the MTD of CPT-11 in combination with carboplatin was less than half the single-agent dose. We conclude that carboplatin is not recommendable for combination with CPT-11 in lymphoma patients. Other suitable agents for such a combination should be sought.
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PMID:Combination phase I/II study of irinotecan hydrochloride (CPT-11) and carboplatin in relapsed or refractory non-Hodgkin's lymphoma. CPT-11/Lymphoma Study Group. 900 51

We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can possess a significant antineoplastic activity when combined with drugs that disrupt de novo thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of the present study was to evaluate the efficacy and the tolerance of the combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed or pretreated, have been enrolled in the trial; the median age was 34 years, 45% had acquired immunodeficiency syndrome before lymphoma and 19 patients had less than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20 patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh patient on, in case of complete or partial remission, the treatment was continued with three additional courses, using AZT at the maximum dose. In 26 evaluable patients, the total (complete + partial) response rate was 77% (95% confidence interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95% confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52% and 31% of the courses, respectively. There was one therapy-related death due to bacteremia followed by septic shock; the only other recorded infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen in HIV-related NHL.
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PMID:3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic combination in the treatment of human immunodeficiency virus-related non-Hodgkin's lymphomas. 900 43


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