净化及非净化自体骨髓移植治疗白血病39例临床研究

报告自体骨髓移植治疗白血病３９例，其中非净化自体骨髓移植（ＡＢＭＴ）１４例，净化自体骨髓移植（ＰＡＢＭＴ）２５例。中位年龄２８岁（１０～４３岁）。ＡＭＬ２７例，ＡＬＬ１０例，ＣＭＬ２例。ＣＲ１３１例，ＣＲ２７例，ＮＲ１例。ＣＲ至移植时间中位数６．７个月（２～１９个月）。预处理方案：ＴＢＩ加Ａｒａ－ｃ、ＤＮＲ或ＶＰ１６。ＡＢＭＴ组及ＰＡＢＭＴ组３年无病生存（ＤＦＳ）率分别为６８．３２％及６７．５７％，复发率为３０．７６％及２６．８０％。但ＰＡＢＭＴ组ＡＭＬ患者３年ＤＦＳ率为８２．３５％及ＣＲ２期移７５％３年ＤＦＳ率为７５％，明显高于ＣＲ。期移植未净化者５０％。化疗组３年ＤＦＳ率为７．３８％及复发率７６．４％，两移植组疗效优于化疗组。     

骨髓增生异常综合征和再生障碍性贫血等细胞遗传学研究

为了探讨骨髓细胞遗传学分析在鉴别诊断骨髓增生异常综合征（ＭＤＳ）和再生障碍性贫血（ＡＡ）等不同血液病中的意义，我们联合应用骨髓细胞Ｒ－带核型分析和姐妹染色单体分化（ＳＣＤ）检测，对３３４例ＭＤＳ、ＡＡ等不同血液病进行分析并随访。结果表明：（１）ＲＡ／ＡＡ、ＲＡ／ＩＴＰ和ＲＡ／ＨＡ等可疑ＲＡ即为不典型ＲＡ或早期ＲＡ；（２）骨髓细胞从ＳＣＤ阳性转为ＳＣＤ阴性是骨髓细胞癌变过程；（３）骨髓细胞ＳＣＤ检测和核型分析具有肯定的诊断和预后价值；（４）ＦＡＢ分类法同细胞遗传学技术相结合可明显地提高ＭＤＳ诊断率或确诊率；（５）ＭＤＳ核型异常检出率６４．４％，与国外（４０％～７０％）相仿。本系列ＭＤＳ常见染色体异常为＋８，２ｑ￣－，一５／５ｑ￣－，一７／７ｑ￣－，７ｐ￣＋，以及一１１，一１４等，也与国外相似。（６）ＭＤＳ发病最初染色体异常看来是染色体数目异常即单体性为主。     

骨髓增生异常综合征和再生障碍性贫血等细胞遗传学…

为了探讨骨髓细胞遗传分析在鉴别诊断骨髓增生异常综合征（ＭＤＳ）和再生障碍性贫血（ＡＡ）等不同血液病中的意义，我们联合应用骨髓细胞Ｒ－带核型分析和组妹染色单体分化（ＳＣＤ）检测，对３３４例ＭＤＳ，ＡＡ等不同血液病进行分析并随访。结果表明：（１）ＲＡ／ＡＡ，ＲＡ／ＩＴＰ和ＲＡ／ＨＡ等可疑ＲＡ即为不典型ＲＡ或异早期ＲＡ；（２）骨髓细胞从ＳＣＤ阳性转为ＳＣＤ阴性是骨髓细胞癌变过程：（３）骨髓细胞ＳＣＤ检测     

强烈化疗治疗小儿急性淋巴细胞白血病临床研究

目的：观察强烈化疗治疗小儿急性淋巴细胞白血病（ＡＬＬ）的疗效。方法：８３ 例ＡＬＬ患儿用ＣＯＤＰＬ方案诱导治疗,缓解后用ＣＡＴ、ＨＤＭＴＸ、ＥＡ、ＶＰＤＬ方案早期巩固强化治疗,用ＭＴＸ、６－ＭＰ、ＶＰ、ＣＯＰ、Ａｒａ－Ｃ维持治疗,用ＣＯＡＰ、ＥＡ、ＶＰＤＬ方案定期加强治疗,用ＨＤＭＴＸ联合三联鞘注对庇护所白血病进行预防。结果：完全缓解（ＣＲ）率９６．４％ （８０／８３）;３ 例在诱导期死于败血症。６８例坚持治疗的患儿,中位随访３７（１８～１０８）个月,５ 年持续完全缓解（ＣＣＲ）率７６．２％ 。标危ＡＬＬ和高危ＡＬＬ的５ 年ＣＣＲ率分别为７９．６％ 和７２．９％ 。结论：强烈化疗及坚持治疗是提高小儿ＡＬＬ５年ＣＣＲ率的关键;严重感染仍是治疗失败的主要原因。     

骨髓增生异常综合征患者T细胞受体基因重排的检测价值

目的 为了解骨髓增生异常综合征（ＭＤＳ）患者Ｔ细胞受体（ＴＣＲ）基因重排情况。方法 应用聚合酶链反应检测３６例ＭＤＳ患者ＴＣＲＶγＩ－Ｊγ基因重排。结果 ８例（２２．２％）ＭＤＳ患者检测出克隆性ＴＣＲＶγＩ－Ｊγ基因重排;难治性贫血伴有原始细胞增多（ＲＡＥＢ）,慢性粒－单细胞白血病（ＣＭＭＬ）和转化中的ＲＡＥＢ（ＲＡＥＢ－Ｔ）组ＴＣＲＶγＩ－Ｊγ基因重排阳性ＭＤＳ转化为急性白血病时间显著短于重排阴     

复方海蛇胶囊治疗老年及老年前期痴呆双盲研究

目的 观察复方海蛇胶囊（ＲＳＣ）治疗老年痴呆的临床疗效。方法 随机双盲法用药，共１０８例，治疗组５８例（单纯ＶＤ２２例、单纯ＡＤ３１例，ＡＤ±ＶＤ５例）；空白对照组５０例（ＶＤ２９例、ＡＤ１８例，ＶＤ合并ＡＤ３例），治疗组服ＲＤＣ，对照组服空白胶囊，均为每例每次６粒，每粒０．２８克，每日三次，疗程３个月。以ＭＭＳＥ、ＨＤＳ、ＷＭＳ评定疗效。结果 ①ＲＳＣ与对照组治后ＭＭＳＥ增值分别为２．８８０±１     

端粒酶在骨髓增生异常综合征中动态改变的研究

我们用端粒酶序列重复扩增银染法：［１］检测了骨髓增生异常综合征（ＭＤＳ）及转为白血病后的端粒酶活性,探讨端粒酶活性在ＭＤＳ中的临床意义。 一、资料和方法 １．对象：２０例均为我院１９９８年４月～１９９９年１２月的住院或门诊成人患者,初发ＭＤＳ１２例,其中难治性贫血（ＲＡ）３例,原始细胞过多型（ＲＡＥＢ）６例,原始细胞过多转化型（ＲＡＥＢ－Ｔ）２例,慢性粒单核细胞白血病（ＣＭＭＬ）１例,ＭＤＳ转为急性白血病（ＭＤＳ－ＡＬ）８例。２０例中男女各１０例,年龄１８～７６岁,平均年龄４７岁,参照文献［２］而…     

重组人红细胞生成素治疗难治性贫血

重组人红细胞生成素治疗难治性贫血吴兴中，王学文，刘海宁，钱晓萍国外近年来应用基因重组人红细胞生成素（ｒＨｕＥＰＯ）治疗难治性贫血已显示一定的疗效，这些难治性贫血包括骨髓增生异常综合征（ＭＤＳ）－难治性贫血（ＭＤＳ－ＲＡ），再生障碍性贫血（再障），骨髓...     

肠病毒RNA和抗ATN抗体在健康献血员中检出的意义

目的：探讨肠病毒ＲＮＡ和抗ＡＮＴ抗体在健康献血员中检出的临床意义。方法：应用酶联免疫吸附实验（ＥＬＩＳＡ）和逆转录－聚合酶链式反应（ＲＴ－ＰＣＲ）方法对健康献血员和扩张型心肌病（ＤＣＭ）患者进行抗心肌多肽自身抗体（抗ＡＴＮＴ抗体）和肠病毒（ＲＮＡ）的检测。结果：４８例健康献血员中有４例抗ＡＮＴ抗体阳性（阳性率为８．３％），３例肠病毒ＲＮＡ阳性（阳性率为６．３％），而４８例ＤＣＭ患者中有３１例抗ＡＮ     

异基因和同基因骨髓移植治疗55~66岁的骨髓增生异常综合征病人

作者用骨髓移植(ＢＭＴ)治疗５０例骨髓增生异常综合征(ＭＤＳ)病人,年龄５５．３~６６．２(中位５８．８)岁。按照ＦＡＢ标准,１３例难治性贫血(ＲＡ),１９例ＲＡ伴原始细胞增多(ＲＡＥＢ),１６例ＲＡＥＢ转化型或急性髓系白血病(ＲＡＥＢ－ｔ/ＡＭＬ),２例慢性粒单细胞白血病(ＣＭＭＬ)。按     

再生障碍性贫血的幼红细胞超微病理

目的:研究再生障碍性贫血患者(AA)幼红细胞病理特点。方法:透射电子显微镜观察和分析16例AA患者骨髓有核红细胞。结果:16例AA患者中,6例为急性再生障碍性贫血(SAA),10例为慢性再生障碍性贫血(CAA)。2例SAA和9例CAA幼红细胞形状不规则,见指状突起和切迹,部分细胞的细胞质空泡化。3例SAA和6例CAA的幼红细胞巨幼样改变明显,细胞核不规则。3例SAA和6例CAA幼红细胞核损伤显著,其中各2例有奶酪样核幼红细胞,共3例幼红细胞出现凋亡。3例CAA患者双核幼红细胞多见。5例SAA和5例CAA患者骨髓含大量单核/巨噬细胞激活和噬血细胞。结论:AA骨髓幼红细胞核与细胞质存在不同形式损伤,单核/巨噬细胞激活和吞噬活跃;红细胞自身发育障碍和单核吞噬激活损伤共同参与了AA病理过程。     

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (>1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia. Am. J. Hematol. 57:113–118, 1998. © 1998 Wiley-Liss, Inc.     

再生障碍性贫血雄激素受体与T细胞亚群的变化

目的:检测慢性再生障碍性贫血(CAA)患者骨髓单个核细胞(MNC)雄激素受体(AR)以及骨髓中T细胞亚群水平,探讨AR在CAA免疫病理机制中的作用。方法:①免疫细胞化学SP法检测CAA患者骨髓MNC内AR的表达水平;②流式细胞术检测CAA骨髓中T细胞亚群(CD3 CD4 细胞、CD3 CD8 细胞)的含量。结果:①CAA患者骨髓MNC中AR阳性水平[(35．18±8．78)个／200个MNC]显著低于对照组[(48．46±9．82)个／200个MNC];不同性别间AR的含量差异无统计学意义。②CAA患者骨髓中的CD3 CD8 细胞含量为(28．54±7．57)％,显著高于对照组。③CAA患者骨髓中的AR阳性水平与骨髓中的CD3 CD8 细胞呈负相关(r=-0．576,P<0．01);而与CD3 CD4 细胞含量未见明显的直线相关关系。结论:CAA患者骨髓AR的表达减少,从而使雄激素刺激造血的作用减弱。患者AR的表达与CD3 CD8 细胞含量呈明显负相关,表明AR的异常可能在一定程度上参与了CAA发病机制中的细胞免疫。     

Clinical features of atypical refractory anemia (RA)

Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.     

All-trans retinoic acid in patients with myelodysplastic syndromes: results of a pilot study

Considering the beneficial effect of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), it has been speculated that ATRA might also be useful for treating other hematologic malignancies. To test this hypothesis, we performed a dose-escalating 3-month-trial of ATRA in 15 patients with primary or secondary myelodysplastic syndromes (MDS). Morphologic diagnoses were refractory anemia (RA) in 4, RA with ring sideroblasts (RARS) in 2, RA with excess blasts (RAEB) in 7, and RAEB in transformation (RAEB/T) in 2 cases. Patients included were required to have one or more of the following criteria: transfusion- dependent anemia, pronounced neutropenia (< or = 0.5 x 10(9)/L) or thrombocytopenia (< or = 20 x 10(9)/L), or increasing blast cells in the peripheral blood or bone marrow. Therapy was started at an ATRA dose of 30 mg/m2/d, administered orally as two doses of 15 mg/m2 every 12 hours. The retinoid dose was increased to 60 mg/m2/d after 4 weeks and to 90 mg/m2/d after 8 weeks. Among 14 patients assessable for response, none obtained a complete or partial remission. Three patients had a minor response, manifested by either reduction in transfusion requirements (2 patients) or increase in neutrophil and platelet counts (1 patient). During the study period, 5 patients progressed to more advanced stages of MDS or overt leukemia. Three patients with chromosomal abnormalities receiving ATRA for a period of 10 to 12 weeks retained their cytogenetic marker after completion of treatment. Side effects of ATRA primarily affected the skin and mucous membranes, with 13 of 15 patients having at least low-grade dermatologic toxicity. In 2 cases, treatment had to be prematurely stopped because of intolerable conjunctivitis or progressive neurologic symptoms. These data suggest that ATRA has little effect on MDS. The lack of response of MDS patients, as compared with those with APL, may be attributed to the absence of the t(15;17) translocation that seems to be a prerequisite for clinical efficacy of ATRA.     

同种异体骨髓移植治疗10例重型再生障碍性贫血患者的远期随访资料分析

目的：提高重型再生障碍性贫血(SAA)患者的长期治愈率。方法：1980年5月一2001年12月采用同种异体骨髓移植(BMT)治疗SAA患者l0例，并对其临床及远期随访资料进行分析。结果：近期死亡4例，转入侵性再生障碍性贫血(CAA)3例，治愈3例。治愈的3例中，l例8年后出现骨髓增生异常综合征(MDS)，以后转变成急性单核细胞白血病。结论：同种异体BMT是治疗SAA的有效治疗方法。加强对感染的防治和移植物抗宿主病(GVHD)的控制是移植后早期阶段的治疗关键。SAA经BMT治疗后的随访结果提示，BMT中的预处理方案有必要加以改进，应作染色体及基因检测，以探讨基因突变是否是AA转化为AC的机制。     

Treatment of myelodysplastic syndromes with all-trans retinoic acid. Leukemia Study Group of the Ministry of Health and Welfare

We treated 23 patients with myelodysplastic syndromes (MDS); 2 refractory anemia (RA) with prior therapy, 11 RA with excess of blasts (RAEB), and 10 RAEB in transformation (RAEB-T), with daily oral 45 mg/m2 all-trans retinoic acid (ATRA) in a multiinstitutional prospective study. In two patients with RAEB and one with RAEB-T, a more than 1,000/microL increase of peripheral neutrophil counts was observed with some reduction of blast percentage in the bone marrow 2 to 9 weeks after the start of ATRA. However, the effect was transient and did not last for more than 5 weeks despite the continuation of ATRA therapy. In one other patient with RA, one patient with RAEB, and one patient with RAEB-T, slight increase of hemoglobin levels or reduction of blast percentage in bone marrow was noted. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, abnormal liver function tests, and high serum triglyceridemia. Although ATRA works remarkably as a differentiation therapy in acute promyelocytic leukemia, its effect in MDS included in this study was modest. Further study of this agent alone or in combination may be warranted in less advanced stages of this disease.     

Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study

Haemopoietic growth factors (HGF), i.e. erythropoietin [recombinant human erythropoietin (rHEPO)] or granulocyte colony stimulating factor (G-CSF), alone or in combination, have largely been used to treat anemia in myelodysplastic syndromes (MDS), but whether combined rHEPO and G-CSF is really superior to rHEPO alone is still under debate. In particular, randomized studies comparing front-line rHEPO vs rHEPO+G-CSF are still lacking. The aim of this study was to compare the effects of “standard” doses of rHEPO with the combination of rHEPO and G-CSF in the treatment of anemic patients with low-risk MDS in a prospective randomized trial. Anemic patients with low-risk MDS were randomly assigned to receive either rHEPO (10,000 IU s.c. three times a week) or the same dosage of rHEPO+G-CSF (300 μg s.c. twice a week) for a minimum of 8 weeks. Patients who were unresponsive to rHEPO were offered the combination therapy for another 8 weeks, whereas non-responders to rHEPO+G-CSF were considered “off study”. Responders continued the treatment indefinitely. Both haematological response and changes in quality-of-life (QoL) scores (Functional Assessment of Cancer Therapy-Anemia) were recorded and evaluated. Thirty consecutive patients [10 refractory anemia (RA), 5 RA with ringed sideroblasts, 7 refractory cytopenia with multilineage dysplasia, 5 RA with less than 10% blasts and 3 5q-syndrome] were enrolled in the study. All of them (15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm) were valuable after the first 8 weeks of treatment. Erythroid response was observed in 6/15 (40%) patients in the rHEPO arm and in 11/15 (73.3%) patients in the rHEPO+G-CSF arm. In 4/9 (44.4%) patients who were unresponsive to rHEPO, the addition of G-CSF induced erythroid response at 16 weeks. No relevant adverse effects were recorded for either treatment in any of the study patients. Erythroid response to HGF was associated with a relevant improvement in QoL. Twenty responders continued the treatment. Afterwards, 8/20 (40%) discontinued therapy because of the following: losing response (2), progression to high-risk MDS (3) and death due to other causes (3). The remaining 12 are still responding and continuing treatment, with a median follow-up of 28 months. Progression to acute leukemia was cumulatively observed in 4/30 (13.3%) patients (2 in each arm). Although our data were obtained from a relatively small cohort of patients, they indicate that the rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in low-risk MDS patients and for making a relevant improvement in their QoL.     

Sweet's syndrome in patient with refractory anemia during recombinant human granulocyte colony stimulating factor therapy]

We present a patient with refractory anemia (RA) who developed Sweet's syndrome during the treatment of recombinant human granulocyte colony-stimulating factor (rhG-CSF). A 30-year-old man was admitted to the hospital for evaluation of anemia. He was diagnosed as MDS (RA). As a phase II study in MDS, rhG-CSF therapy was begun. Fever associated with cutaneous lesion developed over the left shoulder. Antibiotics showed no effects. Skin biopsy revealed Sweet's syndrome. This skin lesion disappeared thoroughly with discontinuance of G-CSF and administration of prednisolone. To examine whether Sweet's syndrome was related to the G-CSF therapy, we analyzed the effect of G-CSF on the function of patient's neutrophils. However, the function of patient's neutrophils was not activated by G-CSF administration.     

The effect of stem-cell factor,interleukin-3 and erythropoietin on in vitro erythropoiesis in myelodysplastic syndromes

An inherent defect of erythroid differentiation at the colony-forming unit blast (CFU-blast) compartment and (or) an impaired response of early erythroid progenitors (BFU-E) to growth stimulation are both considered to contribute to anemia in myelodysplastic syndromes (MDS). With the intention of improving survival and growth of early erythroid progenitors we investigated the effect of stem-cell factor (SCF) and interleukin-3 (IL-3) alone and in combination with erythropoietin, on the in vitro erythropoiesis of 13 patients with MDS and of three normal controls. SCF and IL-3 alone did not promote erythroid colony growth in MDS, while 3 cases responded to erythropoietin alone. In each of these, BFU-E colony growth could be increased by SCF, which was also found in all normal bone marrows. Altogether 6 cases showed a significant enhancement of BFU-E colony numbers by the combination of SCF and erythropoietin as compared to erythropoietin alone (P=0.036). Out of the 6 responding cases, 5 belonged to the FAB-classified subgroups refractory anemia (RA) and refractory anemia with ringed sideroblasts (RA/RS) (5/5), while 1 patient was classified as having refractory anemia with excess of blasts (RAEB) (1/4). No patient with refractory anemia with excess of blasts in transformation (RAEB-T) (0/4) responded. In spite of these positive effects, the absolute number of BFU-E colonies remained reduced in all MDS cases when compared to normal controls. IL-3 proved ineffective in increasing the response to erythropoietin in MDS although it increased erythropoietin-induced BFU-E formation in normal controls significantly. We conclude that the striking synergistic effect of SCF and erythropoietin on erythroid colony formation seen with normal bone marrow is conserved in most cases with RA and RA/RS. In RAEB and RAEB-T the intrinsic defect of the erythroid differentiation pathway cannot be overcome by SCF.Abbreviation MDS myelodysplastic syndrome - SCF stem-cell factor - II-3 interleukin-3 - RA refractory anemia - RA/RS RA with ringed sideroblasts - RAEB RA with excess of blasts - RAEB-T RA with excess of blasts in transformation - Epo erythropoietin