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Haematological Toxicity (haematological + toxicity)
Selected AbstractsHaematological toxicity of drugs used in psychiatry,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Robert J. Flanagan Abstract Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5,10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents. Copyright © 2007 John Wiley & Sons, Ltd. [source] Haematological toxicity of colchicineBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Michael Dickinson No abstract is available for this article. [source] Toxicity in standard melphalan,prednisone therapy among myeloma patients with renal failure , a retrospective analysis and recommendations for dose adjustmentBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Kristina Carlson Summary Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan,prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3,4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30,50 and <30 ml/min respectively. WHO grades 3,4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of ,10 ml/min no conclusions can be drawn for this subgroup. [source] Amelioration of Oxaliplatin Neurotoxicity by Drugs in Humans and Experimental Animals: A MiniReview of Recent LiteratureBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010Badreldin H. Ali The drug is particularly useful alone and in combination with flurouracil and leucovorin in colorectal cancer, but it is also used for other cancers such as those of the ovary, lung, breast and liver, as well as non-Hodgkin's lymphoma. The drug is known to cause neurological, gastrointestinal and haematological toxicities. Neurotoxicity occurs in most of the treated patients and is considered to be a serious limitation for the use of the drug. The mechanism of the neurotoxicity is not known with certainty but may involve prolongation of sodium channels opening. Strategies to ameliorate oxaliplatin neurotoxicity include the use of several ,neuroprotective' drugs. This MiniReview attempts to list and comment on the action and use of some of these agents, which include carbamazepine, gabapentin, calcium and magnesium salts, reduced glutathione, N -acetylcysteine and a few others. None of these drugs have been proven to be effective in large, controlled, clinical trials. [source] High activity 90Y-ibritumomab tiuxetan (Zevalin®) with peripheral blood progenitor cells support in patients with refractory/resistant B-cell non-Hodgkin lymphomasBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2007Pier F. Ferrucci Summary Radioimmunotherapy (RIT) is an alternative approach in the treatment of resistant/refractory B-cell non-Hodgkin lymphoma (NHL). We performed a feasibility and toxicity pilot study of escalating activity of 90Y-ibritumomab tiuxetan followed by autologous stem cell transplantation (ASCT). Three activity levels were fixed , 30 MBq/kg (0·8 mCi/kg), 45 MBq/kg (1·2 mCi/kg) and 56 MBq/kg (1·5 mCi/kg) , and 13 patients enrolled. One week before treatment all patients underwent dosimetry. ASCT was performed 13 d after Zevalin® administration. Treatment was well tolerated and all patients engrafted promptly. No differences in terms of haematological toxicities were observed among the three levels, apart from a delayed platelet recovery in heavily pretreated patients receiving 56 MBq/kg. Non-haematologic toxicity was mainly related to infections and liver toxicity. One patient died 4 months after treatment because of hepatitis C virus reactivation. One patient developed a myelodysplastic syndrome 2 years after treatment. In conclusion, high-activity Zevalin® with ASCT is feasible and could be safely delivered in elderly and heavily pretreated NHL patients, including those who previously received high-dose chemotherapy and ASCT. Maximum tolerated dose was not clearly defined according to dosimetry and clinical toxicities, and further studies are needed to confirm the toxicity profile and evaluate efficacy. [source] Lenalidomide in the treatment of multiple myeloma: a reviewJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2008X. Armoiry PharmD PhD Summary Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide. [source] Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine responseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2010Y. ROTMAN Aliment Pharmacol Ther,31, 1018,1027 Summary Background, Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. Aim, To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses. Methods, A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 ,g/week) and 27 patients with standard doses (180 ,g/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated. Results, Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups. Conclusion, A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing. [source] A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancerRESPIROLOGY, Issue 4 2005Tuncay GOKSEL Objective: Cisplatin-gemcitabine (PG) and cisplatin-etoposide (PE) combinations are active regimens for non-small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC. Methodology: We conducted a prospective, multicentre trial. A total of 166 patients were enrolled into the study and received either gemcitabine (1000 mg/m2) on days 1, 8 and 15 plus cisplatin (80 mg/m2) on day 2 every 4 weeks, or etoposide (100 mg/m2) on days 1, 2 and 3 plus cisplatin (80 mg/m2) on day 1 every 3 weeks. Results: The overall response rate was superior in the PG group (54.8%vs 39.0%, P = 0.045). There was no significant difference in survival between the two groups, with respective median and 1-year survival of 38 weeks and 33.3% for the PG group, and 34 weeks and 23.2% for the PE group. There was also no statistical difference for time to progression between the two groups. Neutropenia and thrombocytopenia were seen more frequently in the PG group (grade 3 neutropenia, 33.3%vs 15.9%, P = 0.012; grade 3 thrombocytopenia, 27.4%vs 3.7%, P < 0.001 and grade 4 thrombocytopenia, 10.7%vs 1.2%, P = 0.018). Conclusion: PG is an active chemotherapy regimen and has a better response rate than PE in advanced NSCLC, although there was no difference in time to progression and overall survival. A higher incidence of haematological toxicity was seen with PG than with PE. [source] Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML)BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Jim A. Murray Summary Acute myeloid leukaemia (AML) causes life-threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two-thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti-AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high-risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22,30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML. [source] ChlVPP/ABVVP, a first line ,hybrid' combination chemotherapy for advanced Hodgkin's lymphoma: a retrospective analysisBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004G. Martinelli Summary We retrospectively analysed toxicities and clinical results of 61 Hodgkin's lymphoma patients treated with chlorambucil, vinblastine, procarbazine, doxorubicin, bleomycin, vincristine and etoposide (ChlVPP/ABVVP), delivered in a weekly alternate schedule. Of 61 patients, 33 were in stages III,IV, 21 in stage IIB and seven in stage IIA with bulky disease or extranodal presentation. ChlVPP/ABVVP was administered for 6,8 cycles. Involved field radiotherapy (IFRT) (30,35 Gy) was delivered to 31 patients with residual disease after chemotherapy or bulky disease at diagnosis. Of 61 patients, 58 (95%) achieved complete clinical or radiological remission after chemotherapy and IFRT. With a median follow-up of 60 months, 5-year overall survival, relapse- and event-free survival were 78·8% (95% CI 68·2,91·1%), 81% (95% CI 70·6,92·2%) and 71·9% (95% CI 68·2,82·2%) respectively. Grades 3,4 neutropenia was the most relevant haematological toxicity and occurred in 82% of patients. Non-haematological toxicities were mild and reversible. No toxic deaths were recorded. One patient developed secondary acute myeloid leukaemia 1 year after ChlVPP/ABVVP. Due to the retrospective nature of this study, no definitive conclusions could be drawn about the clinical activity of ChlVPP/ABVVP. Nonetheless, clinical results seem better than those reported with standard regimens [ABVD (doxorubicin, bleomycin, vincristine, dacarbazine), MOPP (methotrexate, vincristine, procarbazine, prednisone), MOPP/ABVD] and as good as those reported using standard or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), with a lower degree of haematological and non-haematological toxicity. Long-term results of the ongoing randomized trial, comparing ABVD versus high-dose intensity weekly regimens will be useful to confirm our results. [source] | ||||||||||