Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome
Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome
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DOI：
10.1182/blood.v90.9.3364
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发表时间：
1997-11-01
期刊：
影响因子：
20.3
通讯作者：
Capizzi, R
中科院分区：
文献类型：
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作者：
List, AF;Brasfield, F;Capizzi, R
氨硫醇，氨磷汀(乙醇；美国生物科学，西康肖霍肯，宾夕法尼亚州)，是一种细胞保护剂，可以改善抗癌治疗的毒性。在体外，氨磷汀促进原始造血祖细胞的形成和存活，这些原始造血祖细胞来源于骨髓增生异常(BM)标本。为评价氨磷汀对血液学的影响，在一项I/II期研究中，18名骨髓增生异常综合征(MDS)患者和一名或多名难治性红细胞减少症患者接受了氨磷汀治疗。4个队列接受阿米福汀100、200或400 mg/m(2)静脉注射，每周3次，或每周740 mg/m(2)，连续3周，然后观察2周。无反应的患者根据药物耐受性在下一个更高的剂量水平接受第二疗程的治疗。在治疗前和第21天后评估骨髓(BM)祖细胞的生长情况。诊断包括难治性贫血(7例)、环状铁粒细胞难治性贫血(5例)、难治性贫血(RAEB)(4例)和RAEB-in转化(RAEB-t)(2例)。每周三次给药方案治疗的15名患者(83%)出现单系或多系血液学反应。阿米福汀治疗后，14例患者中性粒细胞绝对值增加50%或以上(426~11,348/亩L)，14例血小板减少患者中6例(43%)血小板计数增加(绝对值增加16,000~110,000/亩L)，15例红细胞输注依赖患者中5例输血需求减少50%以上，15例可评价患者中13例可评估造血祖细胞增加，包括CFU-GEMM(12例)、BFU-E(8例)和CFU-GM(6例)。氨磷汀剂量小于或等于200 mg/m(2)耐受性良好，而II级恶心、呕吐和疲劳在较高剂量时是有限的。三名登记前有过多白血病的患者经历了骨髓原始细胞百分比的增加，两名患者演变为急性白血病，并在停药后持续存在。我们得出结论，在MDS患者中，每周三次剂量小于或等于200 mg/m(2)的氨磷汀耐受性良好，并具有血液学活性。(C)1997年由美国血液病学会主办。
The aminothiol, amifostine (Ethyol; U.S. Bioscience, West Conshohocken, PA), is a cytoprotective agent that ameliorates the toxicities of anticancer therapy. In vitro, amifostine promotes the formation and survival of primitive hematopoietic progenitors derived from myelodysplastic bone marrow (BM) specimens. To evaluate the hematological effects of amifostine, 18 patients with myelodysplastic syndrome (MDS) and one or more refractory cytopenias received treatment with amifostine in a Phase I/II study. Four cohorts received intravenous treatment with 100, 200, or 400 mg/m(2) amifostine three times a week, or 740 mg/m(2) weekly for three consecutive weeks followed by 2 weeks observation. Nonresponding patients received a second course of therapy at the next higher dose level depending upon drug tolerance. Bane marrow (BM) progenitor growth was assessed before treatment and after day 21. Diagnoses included refractory anemia (7), refractory anemia with ringed sideroblasts (5), refractory anemia with excess blasts (RAEB) (4), and RAEB-in transformation (RAEB-t) (2). Single- or multi-lineage hematologic responses occurred in 15 patients (83%) treated with the three-times-a-week dose schedule. Fourteen patients had a 50% or greater increase in absolute neutrophil count with amifostine treatment (range, 426 to 11,348/mu L), Platelet count increased in 6 (43%) of 14 patients with thrombocytopenia (absolute increase, 16,000 to 110,000/mu L), and 5 of 15 red blood cell transfusion-dependent patients had a 50% of greater reduction in transfusion needs, Assayable hematopoietic progenitors increased in 13 of 15 evaluable patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM (6). Amifostine doses less than or equal to 200 mg/m(2) were well tolerated, whereas grade II nausea, vomiting, and fatigue was limiting at higher doses. Three patients with excess blasts before enrollment experienced an increase in BM blast percentage and two patients had evolution to acute leukemia that persisted after treatment withdrawal. We conclude that amifostine administered at doses less than or equal to 200 mg/m(2) three times a week is well tolerated and has hematologic activity in patients with MDS. (C) 1997 by The American Society of Hematology.