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1.
Symptomatic or asymptomatic chronic elevation of platelet count can be observed in all forms of myeloproliferative disorders (MPD). Benefits and limitations of the traditional platelet-reducing agents, such as radioactive phosphorus, alkylating agents, hydroxyurea and interferon alpha, are well known and have been largely described. Anagrelide (Agrelin) is an additional newer drug with a selective platelet-lowering effect. We describe our own long-term experience in 6 patients with MPD who were treated with anagrelide as part of a compassionate-use protocol between April 1991 and August 1997. The median duration of therapy was 54 months (range 17 to 75 months), with an overall response rate of 100% (complete and partial response for at least 4 weeks). The initial median platelet count of 1211 x 10(9)/l (range 847 to 2050 x 10(9)/l) was reduced rapidly and lastingly to 570 x 10(9)/l (range 216 to 667 x 10(9)/l) at the time of the last control. Under treatment with anagrelide 4 of the 6 patients showed a reduction of disease-associated symptoms or complications. Adverse reactions were generally mild and transitory, and no interruption or cessation of therapy was required. Development of drug resistance or late adverse events were not observed. Treatment with anagrelide is effective, safe and in our opinion easy to administer. It also appears to be suitable for long-term administration. 相似文献
2.
MD Oertel 《Canadian Metallurgical Quarterly》1998,55(19):1979-1986
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders. 相似文献
3.
Thrombocytosis is the cause of various complications in myeloproliferative disorders. We present the case of a 54-year-old woman with chronic myelogenous leukaemia who developed large ulcers on both lower legs that were refractory to standard treatment. As concomitant thrombocytosis persisted despite treatment with hydroxyurea, the new megakaryocyte inhibitor anagrelide (Agrelin) was administered and led to normalization of the platelet count within 11 days. The leg ulcers started to heal after 2 weeks and disappeared over a period of 5 months. Our findings argue for a pathogenic role of platelets in the development of leg ulcers in patients with thrombocytosis due to a myeloproliferative disorder. 相似文献
4.
SG Taylor MA Donavan RW Sponzo TJ Cunningham J Horton 《Canadian Metallurgical Quarterly》1975,59(6):1127-1130
Twenty-six patients with small cell carcinoma of the lung were treated with a combination of methyl-CCNU (75 mg/m2 orally), cyclophosphamide (750 mg/m2iv), and vincristine (1.4 mg/m2iv) once every 3 weeks and followed for 2-56 weeks (mean, 24 weeks). An average of seven treatments were given per patient. Myelotoxicity was mild to moderate with no white blood cell count (wbc) less than 1000 cells/mm3 and no platelet count less than 25,000 cells/mm3. Six patients (23%) had a wbc of 1000-2000 cells/mm3 and two (8%) had a platelet count of 25,000-75,000 cells/mm3. Sixty-eight persons of the projected dose of methyl-CCNU was given. Fourteen of 22 patients with measurable disease (54%) responded. Of 14 patients who had received no prior treatment 64% responded with a median survival duration of 40 weeks. Complete responses occurred only in patients without prior radiation therapy or chemotherapy. We conclude that methyl-CCNU may be given with an acceptable level of toxicity in an every 3-week schedule and that the combination of cyclophosphamide, methyl-CCNU, and vincristine warrants further evaluation in the treatment of small cell carcinoma of the lung. 相似文献
5.
J Vojácek P Sebesta T Klika P Zdráhal P Sedivy L Bor?vka T Mach 《Canadian Metallurgical Quarterly》1998,77(5):218-221
During a five-year retrospective follow-up period the authors treated a group of 46 patients with the diagnosis of aneurysm of the popliteal artery (AAP). The group comprised 42 men (91%) and 4 women (9%). The mean age was 62 years. In 32 patients (69%) AAP was on both lower extremities, in the remaining 14 (31%) it was unilateral. Forty-one patients (90%) had surgery and a total of 48 AAP were operated. The remainder was treated by conservative methods (10%). The first symptoms of AAP in the investigated group were: claudication in 17%, thromboembolic complications in 46%, rupture of the AAP in 4%. An asymptomatic aneurysm was detected in 33%. RESULTS: The authors did not record any death or occlusion of the reconstruction during hospitalization. When using a vein the primary patency is 100%. When a prosthesis (PTFE) is used the results are worse but still satisfactory and the five-year secondary patency is 85%. Five patients with thromboembolic complications of AAP were successfully treated by i.a. fibrinolysis. In all exclusion of the aneurysm and revascularization of the extremity followed. In the conclusion the authors emphasize the necessity of early surgical treatment as soon as the condition is detected, before the development of thromboembolic complications of AAP. If they develop it is essential to attempt local fibrinolysis and in the second stage revascularization of the extremity, if possible by a vein. 相似文献
6.
KE Lukong MA Elsliger JS Mort M Potier AV Pshezhetsky 《Canadian Metallurgical Quarterly》1999,38(1):73-80
BACKGROUND: The immunological type of heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced thrombocytopenia. This study evaluated the efficacy of recombinant hirudin (r-hirudin or lepirudin), a potent thrombin inhibitor, for anticoagulation in patients with confirmed HIT. METHODS AND RESULTS: Eighty-two patients in this prospective, multicenter study received 1 of 4 intravenous r-hirudin regimens: A1, HIT patients with thrombosis (n=51), 0.4-mg/kg bolus and then 0.15 mg. kg-1. h-1; A2, HIT patients with thrombosis receiving thrombolysis (n=5), 0. 2-mg/kg bolus and then 0.1 mg. kg-1. h-1; B, HIT patients without thrombosis (n=18), 0.1 mg. kg-1. h-1; and C, during cardiopulmonary bypass surgery (n=8), 0.25-mg/kg bolus and then 5-mg boluses as needed. Response criteria were increase in platelet count by >/=30% to >10(9)/L and activated partial thromboplastin time (aPTT) values 1.5 to 3.0 times baseline values achieved with a maximum of 2 dose increases. No placebo control was used for ethical reasons. Outcomes of a subset of r-hirudin-treated patients who met predefined inclusion criteria (n=71) were compared with those of a historical control group (n=120) for combined and individual incidences of death, amputations, new thromboembolic complications, and incidences of bleeding. Platelet counts increased rapidly in 88.7% of r-hirudin-treated patients with acute HIT. In regimens A1 and A2, the 25% and 75% quartiles of the aPTT were within the target range at all but 1 time point. The incidence of the combined end point (death, amputation, new thromboembolic complications) was significantly reduced in r-hirudin patients compared with historical control patients (P=0.014). During first selected treatment, the adjusted hazard ratio for r-hirudin patients versus historical control was 0.279 (95% CI, 0.112 to 0.699; P=0.003). Bleeding rates were similar in both groups. CONCLUSIONS: r-Hirudin treatment is associated with a rapid and sustained recovery of platelet counts, sufficient aPTT prolongations, and true clinical benefits for patients with HIT. 相似文献
7.
G Szücs I Mikó E Ajzner L Póti K Szepesi I Furka 《Canadian Metallurgical Quarterly》1997,36(1-4):356-358
The authors used an antithrombotic agent (Nadroparin Calcium) with anti-Xa effect in their experiments to prevent thromboembolic complications in the model of endoprosthetic replacement of the hip joint in mongrel dogs. 10 experimental animals (Group I.) were given doses of 100 A Xa ICU/kg/bwt of Nadroparin Calcium subcutaneously 4 hours prior to the operation and also once a day until the 3rd postoperative day; between the 4th and 10th postoperative days doses of 150 A Xa ICU/kg/bwt Nadroparin Calcium were given. The 10 control animals (Group II.) did not receive anticoagulant treatment. In both groups platelet count, activated partial thromboplastin times (APTT), prothrombin and fibrinogen levels as well as activated factor X inhibition (F Xa) were measured prior to surgery and also until the 14th postoperative day. No changes in APTT and prothrombin levels were detected during the experiment, however platelet count and fibrinogen levels as well as the extent of F Xa inhibition showed significant and different changes in groups I. and II. The Group I. which had received thromboembolic prophylaxis did not develop deep venous thrombosis or pulmonary embolism, but the control group did. Based on their investigations, the authors concluded that they had been able to achieve F Xa inhibition by giving the above mentioned doses of Nadroparin Calcium which was enough to prevent thromboembolic complications in their model experiment of implanting hip endoprosthesis. 相似文献
8.
A Delannoy A Ferrant P Martiat L Montfort C Doyen G Sokal JL Michaux 《Canadian Metallurgical Quarterly》1994,36(4):311-315
The therapeutic potential of 2-chlorodeoxyadenosine (CdA) in patients with advanced chronic lymphocytic leukaemia (CLL) remains controversial with response rates in clinical trials ranging from 44 to 67%. This report describes our experience with CdA in 22 CLL patients having already undergone previous treatment. CdA was given by continuous intravenous infusion at a dose of 4 mg/m2/day for 7 days (4 patients) or as 2-h intravenous infusions at a dose of 5.6 mg/m2/day for 5 days (18 patients). Partial (n = 5) or complete (n = 2) response was obtained in 7 cases. As compared to unresponsive patients, responding subjects received CdA earlier in the course of their disease (mean interval between diagnosis and CdA therapy 58 vs 102 months), were less thrombocytopenic at initiation of CdA (mean platelet count 165 x 10(9)/L vs 81 x 10(9)/L) and experienced less severe neutropenia during the first course of therapy (mean minimal neutrophil count 1.55 x 10(9)/L vs 0.43 x 10(9)/L). None of 6 patients with CLL refractory to fludarabine responded to CdA. An evaluation of haematological toxicity during the first course of treatment showed grade 4 neutropenia (< 0.5 x 10(9)/L) in 7 cases and grade 4 thrombocytopenia (< 25 x 10(9)/L) in one of 19 cases where the platelet count was greater than 25 x 10(9)/L at initiation of CdA. In comparison with earlier reports, the present series of patients had received relatively heavy prior therapy, experienced more severe haematological toxicity and demonstrated a lower total response rate. 相似文献
9.
PURPOSE: We report our experience with the intravesical administration of oxybutynin chloride with particular focus on the incidence and characterization of untoward effects and inconvenience of therapy. MATERIALS AND METHODS: From 1990 to 1995, 23 children 5 to 11 years old with myelodysplasia were treated with intravesical oxybutynin chloride. Initial dose was 1.25 mg. in 5 cc sterile water instilled during routine catheterization 3 times daily, which was increased as tolerated and clinically indicated. Oral anticholinergic, antispasmodic and sympathomimetic medications were discontinued during therapy. We reviewed therapeutic indications, doses, frequency duration, reason for discontinuation and untoward effects. Patients/parents were surveyed for convenience of treatment as well as side effects and their timing with respect to drug administration and dose. RESULTS: In 15 patients (65%) treatment was discontinued and oral formulations were resumed or other therapy was required due to side effects, ineffectiveness or inconvenience. Seven patients had untoward effects, ranging from facial flushing and dizziness to agoraphobia and hyperactivity. Six patients discontinued therapy due to side effects after 1 day to 2 years (mode 1 month) at doses of 1.25 to 5 mg., including 5 who previously had side effects from oral oxybutynin chloride. Inconvenience of therapy was noted irrespective of the degree of independence of the child for performing intravesical therapy. CONCLUSIONS: Untoward effects and inconvenience are the most common reasons for discontinuing intravesical oxybutynin chloride therapy for neurogenic bladder dysfunction. Children who previously had side effects from oral oxybutynin chloride are more likely to have them during intravesical therapy. 相似文献
10.
The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer. 相似文献
11.
A Sinicco R Raiteri M Sciandra G Dassio G Bechis A Maiello 《Canadian Metallurgical Quarterly》1997,29(6):543-549
PROBLEM: A life-threatening complication of the thrombembolism prophylaxis with heparin is heparin-induced thrombocytopenia (HIT) type II. HIT type II is based on immunological mechanisms. Even low, subcutaneously applied doses may produce HIT type II. In those patients, continued application may cause thromboembolic complications. The most important symptom of HIT type II is a decrease of platelets. METHODS: In a prospective study, we investigated the incidence of HIT type II within the period from 01.07.95 to 30.06.96 in orthopedic patients. We also evaluated the importance of the daily platelet count from the fifth postoperative day for the early diagnosis of HIT type II and a possible reduction of the thrombosis rate. The study included 307 patients after primary implantation of hip and knee endoprosthesis and after hip endoprosthesis replacement. All patients received 3 x 5000 IU/d of unfractionated heparin subcutaneously. Whenever there was a decrease of platelets of at least 50% in relation to the preoperative value or whenever thrombembolic complications occurred, serum was analyzed by the heparin-induced platelet activation test (HIPA). RESULTS: 20 patients developed HIT type II. This corresponds to an incidence of 6.5%. 10 of the HIT type II antibody positive patients (50%) developed thrombembolic complications. 3 patients (0.9%) of the group studied developed clinically symptomatic thrombembolic complications without evidence of heparin antibodies. The total risk of getting thrombembolic complications was 4.2% (13 patients). 3.3% (10 patients) of the entire group developed HIT type II antibody associated thrombembolic complications; 1 patient died. The lethality in the HIT type II antibody positive patient group amounted to 5%. The patients with HIT type II received LMW heparinoid Orgaran (AKZO-Organon, The Netherlands) or hirudin (as a clinical trial). The comparison group (retrospective study from 17.10.92 to 16.10.93) was composed of 262 patients with the same operations and equal thromboembolism prophylaxis. The platelet count was made only as part of routine diagnostic tests. 21 patients (8.0%) developed clinically symptomatic thrombembolic complications. The difference in the thrombosis rate between these two groups of patients is statistically significant. Unrecognized HIT type II is probably the reason for the high thrombembolic complication rate in the comparison group. CONCLUSIONS: The daily platelet count from the fifth postoperative day and from the first day in case of reexposure to heparin is an important measure for the early diagnosis of HIT type II. 相似文献
12.
S Boksovi? M Prci? D Radni? A Atijas Z Budimir IR Saracevic 《Canadian Metallurgical Quarterly》1977,31(1):5-10
One hundred twenty-one patients with disseminated malignant melanoma were treated with BCNU, vincristine, DTIC, and chlorpromazine (BVD). A response rate of 22% was observed; 28% of the patients had stable disease and 50% had increasing disease. Similar response rates were obtained with both the high dose and low dose treatment schedules. Patients who exhibited some degree of improvement during their initial course of treatment had the highest overall response rate (72%) to BVD chemotherapy. The median survival from onset of therapy was six months for all patients and 18 months for patients who responded to chemotherapy. The median duration of response was 9.9 months. Thus, the addition of chlorpromazine to BVD chemotherapy did not increase tumor response, and the overall results obtained were comparable to DTIC alone. Patients were found to be lymphopenic prior to the onset of therapy. Their median absolute lymphocyte count was 1800/mm3. Those patients with absolute lymphocyte counts above the 2710/mm3 normal mean had significantly higher response rates (35% vs. 19%, P less than .05) and longer survivals (9.8 months vs. 4.3 months, P less than .05) than patients with lower initial lymphocyte levels. Pretreatment eosinophil and monocyte counts were not closely correlated with patient response or survival. 相似文献
13.
P Pinton 《Canadian Metallurgical Quarterly》1998,47(5):351-358
ReoPro (abciximab) is the Fab fragment of a chimeric monoclonal antibody directed against platelet glycoprotein IIb-IIIa. Its efficacy to prevent ischaemic complications after PTCA has been demonstrated in 3 studies: EPIC, EPILOG, UPTAKE. One hundred and sixty five cases of thrombocytopenia (< 100,000/microliter) were reported in a series of 5461 patients randomized in these 3 studies (i.e. 3.0%), including 46 (2.03%) with placebo and 119 (3.73% with abciximab. Among the 2270 patients randomized to receive placebo, 11 (0.48%) cases of severe thrombocytopenia (< 50,000/microliter) were observed versus 34 (1.07%) with abciximab. Major acute thrombocytopenia (< 20,000/microliter and < 24 hours) occurred in 0.60% (20 patients) of cases with abciximab. Their mechanism remains unknown. A therapeutic challenge did not modify either their incidence, or their severity. The development of thrombocytopenia did not worsen the patient's prognosis and course was always favourable. Twenty five cases of thrombocytopenia (0.60%), including 3 cases of acute major thrombocytopenia (0.08%) were spontaneously reported in France among the first 4000 patients treated with abciximab post-marketing. All patients treated with abciximab must be monitored by platelet count, 2 to 4 hours after the bolus administration, then 12 and 24 hours later. These platelet counts should be performed on 3 tubes (EDTA, citrate, heparin) in order to eliminate pseudothrombocytopenia and a differential diagnosis. In the case of true thrombocytopenia (< 10,000/l), treatment should be suspended and the platelet count should be repeated daily until return to normal. In the case of thrombocytopenia less than 60,000/microliter, heparin and aspirin should also be systematically discontinued and, below 50,000/microliter, platelet transfusion is justified. 相似文献
14.
JI Almeida R Coats TK Liem D Silver 《Canadian Metallurgical Quarterly》1998,27(2):309-14; discussion 315-6
PURPOSE: We reported a 61% morbidity rate and a 23% mortality rate for the heparin-induced thrombocytopenia (HIT) syndrome in 1983. We subsequently reported in 1987 that with early recognition, immediate cessation of the administration of heparin, and platelet function inhibition, the morbidity rate could be reduced to 23% and the mortality rate to 12%. One hundred recent cases of patients with heparin-associated antiplatelet antibodies (HAAb) have been reviewed to determine whether aggressive screening, early diagnosis, and alternate management could further reduce morbidity and mortality rates. METHODS: The consecutive records of 100 patients with positive platelet aggregation tests were reviewed. Sixty-six patients were male. The patients' ages ranged from 23 days to 92 years. The patients were from vascular (28), cardiothoracic (42), and other (30) services. HIT was suspected in patients who received heparin and had falling platelet counts, platelet counts less than 100,000/mm3, or new thromboembolic or hemorrhagic events. RESULTS: Heparin was not offered to six patients with known HAAb. Twelve patients were successfully treated with antiplatelet therapy and limited reexposure to heparin, and 75 patients were successfully treated with early diagnosis and prompt cessation of heparin. Alternate forms of anticoagulation therapy were used selectively. Seven patients had 11 complications. Three of the seven patients were treated successfully with warfarin anticoagulation and aspirin (2) or with aspirin alone (1). A fourth patient was treated with thrombectomy, hematoma evacuation, and aspirin. A fifth patient underwent thrombolysis and coronary angioplasty in addition to receiving warfarin and aspirin. The sixth patient required two thrombectomies and warfarin. A seventh patient required two thrombectomies and aspirin. HIT was responsible for one of 17 deaths. CONCLUSION: A 7.4% morbidity rate and a 1.1% mortality rate have been achieved in patients with HAAb by aggressive screening, early recognition of HIT, and prompt cessation of the administration of heparin. Platelet function inhibitors and other anticoagulants, including nonreacting low molecular weight heparin, are important adjuncts in the management of the thromboembolic disorders associated with HIT. 相似文献
15.
CA Kennedy JA Pimentel DE Lewis MD Anderson PJ Weiss EC Oldfield 《Canadian Metallurgical Quarterly》1993,168(2):314-317
Trimethoprim-sulfamethoxazole (TMP/SMZ) was given in a crossover study to 130 human immunodeficiency virus-infected patients who had been receiving aerosolized pentamidine; 86 (66%) successfully crossed over to TMP/SMZ without hypersensitivity reactions or hematologic toxicity. No significant changes occurred in mean hemoglobin concentration, leukocyte count, or platelet count between study enrollment and 12-month follow-up. Predominant side-effects, in 41 patients (33.8%), were fever and maculopapular rashes, which resolved promptly with discontinuation of TMP/SMZ. The mean time to first side effect was 12.3 days, and 86% of side effects developed within 30 days. Three patients experienced toxicity serious enough to warrant hospitalization. Of patients with < or = 200 CD4+ lymphocytes/mm3, 57% developed rashes after the cross-over compared with only 27% of patients with higher CD4+ cell counts. Many patients currently receiving aerosolized pentamidine can be safely crossed over without hematologic toxicity or hypersensitivity reactions. 相似文献
16.
M Ruggeri G Finazzi A Tosetto S Riva F Rodeghiero T Barbui 《Canadian Metallurgical Quarterly》1998,103(3):772-777
Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder characterized by the occurrence of thromboembolic episodes, particularly in patients aged > 60 years or with a previous history of thrombosis, and/or by haemorrhages in patients with an exceedingly high platelet count. In these subgroups of patients the use of cytoreductive therapy is beneficial in terms of risk/benefit ratio. Only limited anecdotal data are available on the thrombotic or haemorrhagic risk and survival in young asymptomatic ET patients with a platelet count < 1500 x 10(9)/l. Therefore the optimal management of these patients is unknown. To assess the incidence of thrombosis and haemorrhages in this group of patients we carried out a prospective observational study in a cohort of 65 patients with ET, aged < 60 years, with no history of thrombosis or haemorrhage and platelet count < 1500 x 10(9)/l, and in 65 age- and sex-matched controls. Patients were not treated with cytoreductive therapy until the occurrence of thrombosis or haemorrhage. Arterial or venous thrombotic events were objectively documented both in cases and in controls. The median follow-up was 4.1 years, with an incidence of thrombosis in patients and controls of 1.91 and 1.50 cases/100 patient-years, respectively. The age- and sex-adjusted risk rate ratio was 1.43 (95% CI 0.37-5.4). Only three minor haemorrhagic episodes occurred in patients, with an incidence of 1.12 cases/100 patient-years. Pregnancy and surgery were not associated with thrombosis in these patients. We conclude that the thrombotic risk in young ET patients, with no thrombotic history and a platelet count < 1500 x 10(9)/l, is not increased compared to the normal population and that a conservative therapeutic approach should therefore be considered in these patients. 相似文献
17.
HW Snyder A Mittelman A Oral GL Messerschmidt DH Henry S Korec JH Bertram TH Guthrie D Ciavarella D Wuest 《Canadian Metallurgical Quarterly》1993,71(5):1882-1892
BACKGROUND: Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2-10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions. METHODS: Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRE Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival. RESULTS: Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures. CONCLUSIONS: This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy-associated TTP/HUS, an otherwise fatal disease. 相似文献
18.
A Watanabe T Kakihara K Yamamoto S Kataoka R Okada A Tanaka M Uchiyama 《Canadian Metallurgical Quarterly》1997,39(3):368-370
A 14-month-old boy with refractory idiopathic thrombocytopenic purpura (ITP), who was successfully treated with pulsed high-dose oral dexamethasone therapy is reported. The platelet count increased after six scheduled courses of treatment (10 mg/day x 4 days, six courses). Twenty-four months later, the platelet count remained over 10.0 x 10(4)/microL. No obvious side effects were observed during or after the therapy. This treatment could be taken into consideration not only for adults but also for young children with refractory ITP. It is effective, safe, easy to administer, patient comfort is taken into consideration, and hospitalization duration and costs are minimized. 相似文献
19.
20.
HM Kantarjian SM O'Brien M Keating M Beran E Estey S Giralt S Kornblau MB Rios D de Vos M Talpaz 《Canadian Metallurgical Quarterly》1997,11(10):1617-1620
The aim of the study was to evaluate the activity of decitabine, a hypomethylating agent, in the treatment of patients with chronic myelogenous leukemia (CML) in transformation. Thirty-seven patients with CML in blastic (20 patients) or accelerated phases (17 patients) were treated. Their median age was 52 years; 36 had Philadelphia chromosome-positive disease. Decitabine was given at 100 mg/m2 over 6 h every 12 h x 10 doses (1000 mg/m2) to 13 patients, and at 75 mg/m2 over 6 h every 12 h x 10 doses (750 mg/m2) to 24 patients. In blastic phase, two patients (10%) achieved a complete hematologic response (one with Ph suppression), and three (15%) had a hematologic improvement (marrow CR, platelets <100 x 10[3]/microl), for an overall response rate of 25%. In accelerated phase, six patients (35%) returned to a second chronic phase (two with Ph suppression), one (6%) had a hematologic improvement, and two (12%) had a partial hematologic response, for an overall response rate of 53%. Prolonged myelosuppression was the most significant side-effect. The median time to recovery of granulocytes above 500/microl was 48 days, and to recovery of platelets above 30 x 10(3)/microl, 31 days. Febrile episodes occurred in 25 patients (68%) including documented infections in 17 patients (46%). Decitabine has promising activity in CML. The most significant side-effect is prolonged myelosuppression. Decitabine may show activity in other myeloid disorders such as acute myeloid leukemia and myelodysplastic syndrome, as well as in other hematologic malignancies, alone or with other drug combinations. Its value in the context of stem cell support should also be investigated. 相似文献