自体骨髓移植治疗急性白血病的临床研究

报道采用微波加温42℃持续1小时净化18例急性白血病骨髓后进行自体骨髓移植,未用维持治疗,其中15例已持续缓解3～48个月,1例于移植后3个月复发,2例急性淋巴白血病分别于移植后12、15个月出现中枢神经系统白血病。微波净化是一种有效、简便、经济的骨髓净化方法。     

抗CD25抗体预防移植物抗宿主病在儿童白血病半匹配骨髓移植中的应用

目的　探讨抗 CD2 5抗体用于预防儿童白血病半匹配未去 T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。　方法　 10例儿童白血病患者接受 HL A2 - 3位点不合半匹配骨髓移植 ,移植方法除了供者应用粒细胞集落刺激因子 (GCSF)2 5 0μg促进骨髓及受者应用环孢素 A(CSA ) ,甲氨蝶呤 (MTX) ,抗胸腺细胞球蛋白 (ATG)和霉酚酸酯 (MMF)预防 GVHD综合措施外 ,加用抗 CD2 5单克隆抗体预防 GVHD,剂量各为 2 0 m g,在移植前 2 h和移植后第 4天应用 ,采髓后未去 T细胞输注 ,移植结果与前期未用 Simulect移植组比较。　结果　 10例移植后均获造血重建 ,粒细胞大于 0 .5× 10 9/ L 中位天数是19 d,血小板大于 2 0× 10 9/ L 的中位天数是 2 2 d,骨髓植活直接证据检测证实为完全供者造血。无 1例发生急性 ～ GVHD,未用 Sim ulect对照组急性 ～ GVHD为 5 0 % ,差异有显著性意义。可评价慢性 GVHD的 8例均发生慢性 GVHD,均为局限性慢性 GVHD。中位随访 12个月 (范围 9～ 2 4个月 ) ,2例移植相关死亡 ,1例移植后 14个月复发死亡 ,实际无病生存率是 70 % ,与对照比较差异无显著性意义。　结论　本研究儿童半匹配未去 T细胞骨髓移植应用 Sim ulect,明显降低急性重症 a GVHD发生 ,减少移植相关死亡 ,临床应用安全可行。     

骨髓的体外净化并自身移植5例报告

我们用单克隆抗体(McAb)和兔补体体外净化骨髓中残留白血病细胞后对5例普通型急性淋巴细胞性白血病(CALL)患者进行了自身骨髓移植(ABMT)。抽出的骨髓细胞经McAb55加兔补体两次处理后,CALL抗原(CALLA)阳性细胞清除率可达2～3个对数级,骨髓有核细胞及CFU-GM回收率分别为48.7％～96.9％和39.5％～95.7％。外周血白细胞于移植后11～16d开始回升,14～29d升至1×10~9/L以上。23～53d出洁净室。例3于移植后4个月白血病复发, 8.2个月死亡。另4例无病活存分别为19~+、18~+、12~+和6~+个月,远期疗效正在定期随访中。     

高难度异基因骨髓移植成功3例分析

目的 探讨移植条件不完全理想的疑难病例,进行异基因骨髓移植的方法。方法 2例急性粒细胞白血病患者与骨髓供者的血型不同,其中1例为父子间骨髓移植的特殊病例;另1例急性淋巴细胞白血病患者,第三次白血病复发,肺功能异常。患者按环磷酰胺加全身照射预处理,血型不同的供者骨髓,采用离心法分离血浆。结果3例患者异基因骨髓移植成功,2例生存期超过半年。结论 尽管异基因骨髓移植难度大、要求高,但是经过周密计划、精心治疗,仍能成功地进行疑难病例的异基因骨髓移植。     

异基因外周血造血干细胞移植后造血细胞嵌合状态的分析

为评估异基因外周血造血干细胞移植（ALLO－PBSCT）后的植入状况，采用细胞遗传学分析结合短串联重复序列－聚合酶链反应（STR－PCR），对30例Allo-PBSCT病人进行了1－25个月的随访观察。结果表明，不同性别移植的23例，21例完全嵌合（CC），1例混合嵌合（MC），1例为完全受者核型；相同性别移植的慢性髓性白血病（CML）7例，除2例外，其余均未检测到Ph染色体；STR－PCR检测结果与染色体分析结果完全一致。说明两种方面具有互补性，可结合使用。     

山东"10·21"辐射事故病人细胞遗传学动态观察

目的 评价山东"10·21"辐射事故2例严重放射病患者接受异基因外周血造血干细胞移植(Allo-PBSCT)后的植入状态.方法 通过常规染色体畸变(CA)分析、R显带核型分析及微核(MN)法对外周血样本和(或)骨髓样本进行细胞遗传学动态分析.结果 所获数据证明2例患者移植成功(为完全嵌合状态),植入状态稳定,骨髓与外周血的细胞遗传学分析结果基本一致.结果与用短串联-聚合酶联反应(STR-PCR)检测的植入情况及临床表现相符.结论 对急性放射病患者受照射后动态观察双 环畸变和MN检测可作为Allo-PBSCT后评价植入状态的指标.此外,在外周血淋巴细胞急剧减少的情况下,用骨髓样本进行细胞遗传学分析优于外周血样本.     

胎肝低分子抑瘤物净化骨髓技术在白血病自体移植中的应用

7例急性白血病经胎肝低分子抑瘤物净化骨髓后进行了自体骨髓移植,移植时早期复发病例分别于2、18个月复发。缓解期移植5例,1例13个月复发,余例无病存活27,5(12—46)月。笔者对影响移植效果诸多因素进行讨论并说明本净化方法安全可行。     

供者淋巴细胞输注(DLI)治疗恶性血液病异基因骨髓移植后复发

异基因骨髓移植(allo-BMT)应用30多年来已使无数恶性血液病患者获得新生.起初认为allo-BMT的抗白血病效应仅依赖清髓性预处理方案中大剂量化放疗效应,输注不被肿瘤污染的供者骨髓只不过起干细胞救援功效,近来发现移植物中供者T细胞诱导的移植物抗白血病效应(GVL)也起重要作用,尤其对控制移植后复发尤为突出.DLI的出现改变了人们对allo-BMT治疗理论的认识,DLI诱导CML移植后复发再次完全缓解(CR)肯定了其治疗价值.     

供者淋巴细胞输注（DU）治疗恶性血液病异基因骨髓移植后复发

异基因骨髓移植(allo-BMr)应用30多年来已使无数恶性血液病患者获得新生。起初认为allo-BMT的抗白血病效应仅依赖清髓性预处理方案中大剂量化放疗效应，输注不被肿瘤污染的供者骨髓只不过起干细胞救援功效，近来发现移植物中供者T细胞诱导的移植物抗白血病效应(GVL)也起重要作用，尤其对控制移植后复发尤为突出。DLI的出现改变了人们对allo-BMT治疗理论的认识，DLI诱导CML移植后复发再次完全缓解(CR)肯定了其治疗价值。     

急性髓细胞白血病的细胞遗传学特征分析及其诊断预后价值

目的：探讨急性髓细胞白血病（AML）患者的细胞遗传学异常特征及其与诊断、治疗、预后的关系。方法：采用短期培养法制备骨髓细胞染色体，并以R带显带技术对76例初诊AML患者进行染色体核型分析。结果：本组76例中有47例（61．8％）出现染色体异常。共有9种主要的染色体异常核型，t（15；17）及t（8；21）为最常见的染色体结构异常，且t（15；17）及t（8；21）分别只见于急性早幼粒细胞白血病（M3）及急性髓细胞白血病（M2）患者，核型异常与临床完全缓解率及完全缓解持续时间等预后因素高度相关。结论：61．8％的AML患者有染色体异常，特异性的核型异常与特定的FAB亚型相关，是AML诊断和分型的一个重要指标，并有重要的预后意义。     

自体骨髓移植与混合HLA半相合异体骨髓的自体骨髓移植治疗恶性血液病的比较

目的 :提高自体骨髓移植 (ABMT)治疗恶性血液病的疗效 ,减少移植后疾病的复发。方法 :比较了液体培养净化的ABMT和混合 1/ 6量的HLA半相合异基因骨髓有核细胞的ABMT在恶性血液病中的应用 ,对ABMT组 11例和混合移植组 2 3例的疗效进行了随访和分析对比。结果 :ABMT组除 2例移植早期死亡 ,余 9例皆重建造血功能。混合移植组 4例早期死亡 ,余 19例皆成功造血重建。后者外周血三系细胞造血恢复均慢于前者 ,但无明显的统计学差异 (P >0 .0 1)。ABMT组无病存活 4例(36 .4% ) ,平均随访 48(34～ 92 )个月均CCR。混合移植组无病存活的 10例 (43.5 % ) ,中位随访 2 5 (16～ 6 5 )个月 ,仍存活 ,且均CCR。移植相关死亡ABMT组为 18.2 % ,混合移植组为 17.4%。ABMT组复发率为 44 .4% ,混合移植组为 31.6 %。混合移植组有 6例发生轻度皮肤型GVHD ,激素治疗后渐好转。二组病人皆未观察到急性GVHD。结论 :混合移植对恶性血液病的疗效优于ABMT ,并具有方法简便安全的特点。     

异基因骨髓移植的植入证明

本文对我院1987年12月至1989年11月间进行的9例HLA相合的异基因骨髓移植供受者的植入情况做了分析。我们采用了国际骨髓移植登记处的移植成功指标,及常规的细胞遗传学检查,结果全部患者均有间接的临床植入证据,其中5例有直接的细胞遗传学证据。本文综合文献提示,细胞遗传学分析在移植证明中具有很重要的意义,但其缺陷也是显而易见的。DNA-RFLP的检测可弥补常规方法的缺陷,并获得准确可靠的植入依据。     

对两例骨髓移植病人预处理方案的认识

本文总结了两例白血病病人骨髓移植的情况,介绍了他们组织相容性抗原匹配程度、预处理方案和移植骨髓的有核细胞数。并对两例移植的不同结果与预处理方案的关系,结合文献作了讨论。     

一种表现为皮肤胶原沉着病的小鼠慢性移植排斥模型的建立

目的建立一种小鼠慢性移植排斥模型。方法将6～8周龄BALB／c（雌性）小鼠经6Gy”Co全身照射后随机分为同基因移植组和异基因移植组。并基因组尾静脉输注未经照射的BIO．D2（雄性）小鼠的骨髓细胞和脾细胞的混合悬液。移植术后通过小鼠性染色体基因组检测、组织病理学分析,以及流式细胞仪和实时定量PCR检测确定小鼠病变的发生。结果病理学分析显示,异基因组小鼠主要表现为皮肤损伤,与同基因组相比,皮肤明显增厚,皮肤弹性降低,真皮层炎性细胞浸润,毛囊和脂肪减少或消失,大量的纤维组织增生,皮下组织出现明显结构改变;性染色体基因组分析显示,畀基因组受者小鼠皮肤内有供者小鼠细胞的浸润;流式结果显示,畀基因组小鼠皮肤内CDllb、CIM5和CD3表达明显增强;实时定量PCR检测结果显示,异基因组小鼠皮肤RANTES、TGF．8,以及胶原蛋白ImRNA水平明显升高。结论与同基因组小鼠相比,异基因组小鼠表现为皮肤胶原沉着病损伤;CDllb’、CD45’和CD3’细胞以及趋化因子RANTES和细胞因子TGF—p】参与了这一病理过程的发生。本研究建立了一种表现为皮肤胶原沉着病的小鼠慢性移植排斥反应模型,为相关后续研究提供了有益的基础。     

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.     

Human identification and sex determination of dental pulp,bone marrow and blood stains with a recombinant DNA probe

Summary Recombinant DNA hybridizing specifically to a 300 nucleotide repeat DNA sequence (BLUR8) of human specificity and to human repeat DNA sequence (pHY10) on the Y chromosome was used for human identification and sex determination of degraded DNA samples of blood stains, dental pulp, and bone marrow. This radioactive technique enabled reliable and sensitive human and sex determination from blood stains that were more than 80 years old. Less than 1 piece of 0.5 cm length thread of blood stain was enough for both tests. DNA from relatively fresh dental pulp and bone marrow was clearly identified. The human identification test, which could recognize up to 0.3 ng DNA correctly, was 3 to 5 times more sensitive than the sex determination test.     

非清髓异基因造血干细胞移植后急性白血病复发5例报告

目的 研究分析非清髓异基因外周造血干细胞移植(NAST)后急性白血病复发的相关因素。方法 29例急性白血病患者NAST后5例复发，男2例，女3例，中位数年龄36岁(18～59岁)。非清髓预处理方案：环磷酰胺、阿糖胞苷及CD3单克隆抗体，3例患者在此基础上加用氟达拉滨。结果 5例均顺利渡过造血抑制期。2例早期形成供者造血细胞完全嵌合体(FDC)并在FDC状态下复发。3例移植早期形成供受者混合造血细胞嵌合体(MC)，2例转为FDC后复发，1例在稳定MC状态下复发。5例中4例复发前无急性或慢性移植物抗宿主疾病(GVHD)，另1例NAST后发生Ⅱ度aGVHD并在皮肤慢性GVHD未治愈状态下复发。5例中1例行2次NAST治疗，在第2次完全缓解，但于2个月后再次复发，放弃治疗。另4例未再继续治疗，2例分别于复发后1和2个月死亡，2例仍带病存活。结论 NAST简便安全，并发症少，白血病复发率无明显升高，为治愈白血病提供了新手段。     

自体造血干细胞移植治疗恶性血液病

为探讨恶性血液病的有效治疗方法,应用自体骨髓移植(ABMT)38例,自体外周血造血干细胞移植(ABSCT)13例,自体外周血造血干细胞与自体骨髓联合移植15例。治疗白血病54例,恶性淋巴瘤11例,多发性骨髓瘤1例。外周血造血干细胞采用化疗加多抗甲素或C—CSF动员。移植物采用微波、阿克拉霉素净化处理。结果:两组动员方案均有良好动员效果。ABSCT组及联合移植组造血功能恢复比ABMT组快(P<0.05),合并症少。66例中,45例仍呈持续缓解(CCR),中位CCR时间32(5～98)个月,复发21例。3年无病生存率及复发率分别为68.5％及26.1％。结果表明:自体造血干细胞移植是根治恶性血液病的有效手段。ABSCT及联合移植具有造血功能恢复快,合并症少等优点。微波和阿克拉霉素体外净化移植物是一种简便、有效的净化方法。     

Second allogenic bone marrow transplantation after late graft rejection in a patient with severe aplastic anemia

Allogeneic bone marrow transplantation (BMT) is the treatment of choice in young patients (pts) with severe aplastic anemia (SAA) who have an HLA identical sibling donor. Late graft rejection to following allogeneic BMT for SAA is a significant clinical problem and is associated with a high risk of mortality. The optimal treatment strategy for patients with late graft rejection after first BMT is still an open question. We report 12-year-old patient with acquired SAA who underwent BMT from his HLA identical sister. BMT was first-line treatment within 3 months of diagnosis. Preparative therapy was Cyclophosphamide (Cy) 200 mg/kg body mass (BM) during 4 days. Graft versus host disease (GVHD) was prevented with Methotrexate (MTX), Methylprednisolone (MPDN) and Cyclosporin A (CsA). After 17 months, during which patient was with normal blood counts and full donor chimaerism, graft rejection occurred. The patient was re-engrafted from the same donor after conditioning with Cy 200 mg/kg BM plus horse antithymocyte globulin (ATG)--2 vials (á 25 mg)/10 kg BM over 4 days. Before the collection, donor's bone marrow was activated with low dose rhGM-CSF (3 micrograms/kg one day). Following a secondary BMT engraftment has sustained. The patient is alive with full donor chimaerism 26 months from secondary transplantation, without acute or chronic GVHD.     

Prognostische Faktoren und Einfluß der Strahlentherapie bei Behandlung differenzierter Schilddrüsenkarzinome

Purpose

In the treatment of differentiated thyroid carcinomas the indication for adjuvant radiotherapy is discussed contradictory. The following study analyzes the long-term survival rates of patients with follicular and papillar thyroid carcinomas after percutaneous radiotherapy.

Patients and Method

Records of 178 patients with differentiated thyroid carcinomas (132 female, median age 46 years: 46 male, median age 47 years) were evaluated. Following thyroid-resection and radioiodine therapy external beam irradiation was performed with a telecobalt device and high energy electrons (mean reference dose 54.7 Gy). Hundred and twenty patients (67.4%) had a histologically confirmed papillary carcinoma, 58 (32.6%) patients had follicular carcinoma. In the group with papillary carcinoma 57 patients (47.5%) were classified as stage I, 11 patients (9.2%) as stage II, 48 patients (40.0%) as stage III, 4 patients (3.3%) as stage IV, respectively, in the group with follicular carcinoma 21 patients (36.2%) were classified as stage I, 4 patients (6.9%) as stage II, 28 patients (48,3%) as stage III and 5 patients (8.6%) as stage IV. Survival, recurrence rate and prognostic factors were analyzed.

Results

The 10-year relapse free survival for the patients with papillary carcinoma was 95.1%, with follicular carcinoma 87.6%. Twelve patients (6.7%), all over 45 years old, died from tumor disease. In the group with papillary carcinoma females showed significantly higher relapse free survivals than males. The 10-year relapse free survival depended on tumor grading: G1 100%, G2 90%, G3 81.7%, G4 78.1%, and stage of disease: I 100%, II 100%, III 88.6%, IV 28.2%. After radiotherapy 150 patients (84.3%) presented no evidence of metastases and had a 10-years relapse free survival of 99.2% After percutaneous radiotherapy locoregional lymph node metastases occurred in 4 patients with follicular carcinoma (6.9%) and 7 patients with papillary carcinoma (5.5%). In this group the 10-year relapse free survival was 66.7%. Distant metastases were observed in 8 patients with follicular carcinoma (13.8%) and 7 patients with papillary carcinoma (7.5%) which occurred in 15 cases (88.7%) after radiotherapy. In this group the 10-year relapse free survival was 43.7%. Recurrences after radiation therapy were observed in 2 cases (3.4%). only in the patients with follicular carcinomas.

Conclusion

Age and Sex of the patients, histologic grading, lymph node status and the UICC-stage of disease are significant prognostic factors. The described results demonstrate that adjuvant percutanous radiotherapy is indicated in patients with carcinoma Stage III/IV or with lymph node involvement.