自体CIK细胞输注在老年多发性骨髓瘤维持治疗中的临床观察

目的:评估自体CIK细胞输注在老年多发性骨髓瘤(MM)维持治疗中的有效性和安全性。方法:选取5例已获得完全缓解或部分缓解的老年MM患者,采集外周血单个核细胞,在体外经干扰素-γ、白细胞介素-2、抗CD3单克隆抗体诱导成CIK细胞,分次回输至患者体内,总量为(1~3)×1010。1个月为1个疗程,连用3个疗程,再3个月为1个疗程,观察疗效和生活质量。结果:随访9~23个月,5例患者共接受了32个疗程的CIK细胞治疗,不良反应少而轻微,输注后CD3+、CD3+CD8+、CD3+CD56+细胞比例显著增高(P0.05),能有效杀伤残留肿瘤细胞,维持疾病缓解状态,提高生活质量(P0.05)。结论:自体CIK细胞输注用于本组5例老年MM患者的维持治疗安全有效。     

应用自体肿瘤免疫细胞治疗中晚期肿瘤的意义

目的探讨树突状细胞(dendritic cells,DCs)和细胞因子诱导的杀伤细胞(cytokine induced kil-ler,CIK)联合化疗治疗晚期实体瘤的临床意义。方法采用自体肿瘤免疫细胞治疗晚期实体瘤患者130例。分离外周血单个核细胞,其中贴壁细胞用粒细胞巨噬细胞集落刺激因子、肿瘤坏死因子及白细胞介素4等诱导产生DCs,并用自体肿瘤细胞或外源性肿瘤细胞抗原致敏,获得Ag.DCs;悬浮细胞经干扰素-γ、IL2和CD3单克隆抗体(CD3 monoclonal antibody,CD3mAb)等诱导产生CIK细胞,将DCs与CIK细胞共同培养;采用FCM法检测DCs及CIK细胞表型,一次回输患者。结果 130例中晚期肿瘤自体肿瘤免疫细胞联合化疗治疗后,完全缓解(CR)5例,部分缓解(PR)19例,稳定(SD)87例,疾病进展(PD)13例,6例晚期肿瘤进展死亡,疾病控制率85.38%。结论 DCs-CIK细胞联合化疗治疗中晚期恶性实体瘤安全有效,具有重要的临床意义和应用前景。     

重组人血管内皮抑制素联合替莫唑胺治疗复发高级别胶质瘤的临床研究

目的观察重组人血管内皮抑制素(恩度)联合替莫唑胺(TMZ)与单纯应用TMZ治疗复发高级别胶质瘤患者的安全性与疗效。方法将74例复发高级别胶质瘤患者随机均分为两组,一组单纯应用TMZ化疗(37例),另一组应用恩度联合TMZ联合化疗(37例)。TMZ化疗方案的选择基于患者O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达状况和既往TMZ化疗效果,采用个体化的治疗。恩度剂量为15 mg静脉滴注,连续应用14 d,间歇2周重复。结果 37例单纯TMZ化疗患者共接受129周期化疗,中位3次(1~10次)。完全缓解(CR)1例(2.7%),部分缓解(PR)9例(24.3%),微效(MR)3例(8.1%),疾病控制率(CR+PR+MR)为35.1%。中位无进展生存期(PFS)为4个月(95%CI 1.9~6.1个月),6个月的PFS率为27.0%。37例恩度联合TMZ化疗患者共接受200周期化疗,中位6次(2~10次)。CR 3例(8.1%),PR 14例(37.8%),MR 6例(16.2%),疾病控制率(CR+PR+MR)为62.1%。中位PFS为6个月(95%CI 4.9~7.1个月),6个月的PFS率为43.0%。不良反应中,同单纯TMZ组相比,恩度联合TMZ组具有更高的高血压发生率。结论恩度联合TMZ化疗较TMZ单药化疗在复发高级别胶质瘤的治疗有更好的客观疗效,相对延长PFS,且具有较好的安全性。     

mFOLFOX6化疗配合自体CIK细胞对晚期大肠癌患者T淋巴细胞亚群的影响

目的:观察m FOLFOX6化疗配合自体细胞免疫疗法(cytokine-induced killer,CIK)对晚期大肠癌患者T淋巴细胞亚群的影响.方法:选取郑州大学附属郑州中心医院2009-01/2014-12收治的同时符合纳入和排除标准的晚期大肠癌患者89例,将其采用随机综合平衡序贯法分为联合组(29例)、化疗组(30例)和CIK组(30例).化疗组给予单纯m FOLFOX6方案化疗,CIK组给予单纯自体CIK细胞治疗,联合组给予m FOLFOX6化疗配合自体CIK细胞治疗.观察比较近期疗效、治疗前后3组患者T淋巴细胞亚群(CD3、CD4、CD8、CD4/CD8)水平变化及不良反应.结果:3组近期疗效等级比较差异有统计学意义(P0.05),且联合组临床获益率远高于化疗组和CIK组(86.2%vs 53.3%,56.7%)(P0.05),而化疗组和CIK组间比较无显著差异(P0.05);治疗前3组CD3、CD4、C D8、C D4/C D8水平差异均无统计学意义(P0.05),治疗后联合组无明显变化(P0.05),而化疗组和CIK组CD3、CD4和CD4/CD8均显著降低(P0.05),CD8明显升高(P0.05),且治疗后联合组均明显优于化疗组和CIK组(P0.05),而化疗组和CIK组间比较无显著差异(P0.05);联合组不良反应发生率为17.2%,化疗组为46.7%,CIK组为10.0%,联合组和CIK组较化疗组显著降低(P0.05).结论:采用m FOLFOX6化疗配合自体CUK细胞治疗晚期大肠癌患者近期疗效显著,且C I K细胞治疗可以避免化疗引起的T细胞亚群功能紊乱,减少不良反应,具有推广价值.     

自体DC-CIK细胞联合替吉奥治疗中晚期肝癌的疗效

目的探讨中晚期肝癌患者行自体DC-CIK细胞联合替吉奥治疗的临床疗效及不良反应。方法采集48例中晚期原发性肝癌患者外周血单个核细胞,加入细胞因子定向诱导DC及CIK,8 d后将扩增的DC及CIK细胞以静脉回输的方式,对患者进行自体DC-CIK细胞输注治疗,同时联合口服替吉奥治疗。结果自体DC-CIK联合替吉奥治疗12 w后CR0例PR 10例,SD 22例,PD 16例,总有效率(RR)为20.8%,疾病控制率(DCR)为66.7%。患者免疫功能提高,生活质量改善。结论自体免疫细胞联合替吉奥治疗中晚期肝癌疗效尚可,副作用小,安全性好。     

CIK细胞联合二线化疗治疗晚期肺癌的临床效果观察

目的观察CIK(Cytokine-induced-killer)细胞联合二线化疗对一线化疗治疗失败的晚期肺癌患者的临床治疗效果。方法将2012年10月~2014年2月,40例经一线化疗无效的晚期肺癌患者随机分为两组:CIK细胞联合二线化疗药物组(n=21)和单用二线化疗药物组(n=19)。对两组的疾病控制率、缓解率、无疾病进展期和生存期进行观察比较。结果 CIK细胞联合化疗组的ORR(Objective response rate,客观缓解率)和DCR(Disease control rate,疾病控制率)分别达到33.3%和81.0%,而单用化疗药物治疗组ORR和DCR分别为15.8%和63.2%(PORR=0.361,PDCR=0.366)。CIK细胞联合化疗组的PFS(中位无疾病进展期)和OS(中位总生存期)分别为5.5个月(95%CI 3.71~7.29个月)及13.8个月(95%CI 10.75~16.85个月),相比而言,单用化疗药物组则分别为3.0个月(95%CI 2.68~3.32个月)及9.5个月(95%CI 8.38~10.62个月)。联合治疗组的患者有着明显更长的PFS和OS(PPFS=0.024,POS=0.042)。结论 CIK细胞联合二线化疗药物治疗一线化疗失败的晚期肺癌患者比单用二线化疗药物治疗可明显延长患者的PFS和平均存活时间。     

自体CIK联合rhIL-2对B细胞恶性淋巴瘤患者T细胞亚群及β2微球蛋白水平的影响

目的探讨自体细胞因子诱导杀伤细胞(CIK)联合重组人白细胞介素(rh IL)-2对B细胞恶性淋巴瘤患者T细胞亚群及β2微球蛋白水平的影响。方法接受CIK联合rh IL-2治疗的46例B细胞恶性淋巴瘤患者为观察组,并选择同期未接受CIK联合IL-2治疗的46例B细胞恶性淋巴瘤患者为对照组。比较两组T细胞亚群、β2微球蛋白、生活质量及临床疗效。结果治疗后,观察组CD3~+、CD3~+/CD8~+、CD3~+/CD56~+水平均比同组治疗前及对照组高(P<0.05);β2微球蛋白比同组治疗前及对照组低(P<0.05);观察组临床疗效总缓解率高于对照组(P<0.05);观察组躯体功能、角色功能、认知功能、情绪功能、社会功能得分均比同组治疗前及对照组高(P<0.05)。结论在B细胞恶性淋巴瘤患者中应用自体CIK联合rh IL-2方案效果显著,可有效改善T细胞亚群和β2微球蛋白水平,提高生活质量,且安全性高。     

DC、CIK白体回输对化疗后胃癌患者T淋巴细胞亚群及NK细胞的影响

目的研究树突状细胞（DC）与细胞因子诱导的杀伤细胞（CIK）自体回输对化疗后胃癌患者T淋巴细胞亚群及NK细胞的影响。方法将92例胃癌患者随机分为观察组及对照组各46例,两组均行常规化疗,观察组于化疗结束后1个月实施DC、CIK自体回输治疗,治疗时间〉2个疗程。采集两组化疗前后及观察组DC和CIK自体回输之后4周的外周血,以流式细胞仪对外周血T淋巴细胞亚群及NK细胞进行检测。结果两组化疗后CD;、CD4＋、CD4＋／cDf、NK水平均明显降低,观察组DC与CIK回输后CD^＋3、CD^＋4、CD^＋4／co^＋8、NK水平明显高于本组及对照组化疗后,P均〈0．05。结论化疗后胃癌患者DC、CIK白体回输后CD^＋3、CD4^＋4、CD^＋4／CD^＋8、NK水平升高,即细胞免疫功能得到改善。     

MEA方案治疗成人急性白血病临床研究

目的观察MEA方案治疗初治、复发或难治急性白血病(AL)的临床疗效及毒副作用。方法43例急性白血病患者均采用MEA方案诱导治疗,其中急性髓细胞白血病(AML)19例、急性淋巴细胞白血病(ALL)20例,急性混合性白血病(AHL)4例;初治22例,复发8例,难治性13例。结果①疗效43例患者中30例(69.77%)获得完全缓解(CR),6例(13.95%)获得部分缓解(PR),总有效率83.72%;AML患者CR率73.68%,PR率15.79%,总有效率89.74%;ALL患者CR率75%,PR率5%,总有效率80%;AHL患者CR率25%,PR率50%,总有效率75%;初治患者CR率81.82%,PR率4.55%,总有效率86.36%;复发、难治患者CR率57.14%,PR率23.81%,总有效率80.95%。②化疗不良反应化疗后骨髓抑制期,WBC低于1.0×109/L、ANC低于0.5×109/L、PLT低于20×109/L于化疗开始后出现的中位时间分别为第9天、第9天和第10天,中位持续时间分别为8、9和8d。30例(69.77%)患者出现发热,其中8例(26.67%)血培养检出病原菌;3例(6.98%)发生结核复燃。6例患者于化疗及恢复期间死亡,其中4例死于败血症、DIC;2例死于颅内出血;化疗相关死亡率13.95%。③随访随访时间224个月,中位随访时间8个月,中位持续CR时间7个月。结论MEA方案对于初治、复发及难治AL均可取得良好的诱导缓解疗效,但其骨髓抑制较重而持久,使用时应结合强力的支持、对症治疗及血液学监测。     

自体CIK细胞回输治疗对晚期肺癌患者免疫功能及生活质量的影响

目的分析自体CIK细胞回输治疗对晚期肺癌患者免疫功能及生活质量的影响,为临床治疗方式的选择提供支持。方法按研究需要对近两年内我院治疗的晚期肺癌患者进行筛选,选取的76例为研究对象。将其随机分为观察和对照组。分别予以单纯化疗治疗和化疗联合自体CIK细胞回输治疗。并组间比较及分析外周血CD4+、CD8+和CD4+/CD8+等T淋巴细胞亚群,KPS评分及生活质量等数据。结果观察组治疗后CD4+、CD8+和CD4+/CD8+等数据均具有显著优势(P0.05);观察组治疗后KPS评分具有显著优势(P0.05);观察组治疗后3个月的生活质量评分显著高于对照组(P0.05)。结论自体CIK细胞回输治疗用于晚期肺癌的辅助治疗能够提升患者的免疫功能和生活质量,对改善患者的生存时间和生活质量均具有重要意义。     

Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts

Cytokine-induced killer (CIK) cells are CD3(+)CD56(+) non-major histocompatibility complex (MHC)-restricted immune effector cells. The present report demonstrates that it was possible to expand CIK cells obtained at diagnosis from patients with acute leukaemia. The percentage of CD3(+)CD56(+) CIK cells generated following culture ranged between 7.6% and 65% (median of 35.3%) and these cells were able to kill the human natural killer target K562 cells. Although the same effector cells were able to lyse autologous acute myeloid leukaemia (AML) target cells, they were not able to lyse autologous acute lymphoblastic leukaemia target cells. Pre-absorption of the CIK effector cells by K562 cells did not completely abrogate the cytotoxicity of CIK cells against autologous blasts in 9 out of 12 samples tested. Moreover, it was observed that the cytotoxicity generated by the CIK effector cells against allogeneic leukaemic blasts was similar to that against autologous blasts. The present study suggests the potential application of CIK cells in the immunotherapy of AML, either in minimal disease state, as donor lymphocyte infusion in relapse post allogeneic transplant, or in cases of chemotherapy refractory leukaemia.     

DC-CIK联合化疗治疗晚期非小细胞肺癌的近期疗效观察

目的探讨DC-CIK联合化疗及常规化疗治疗晚期NSCLC患者的近期疗效。方法 64例临床确诊的晚期NSCLC患者随机分为两组,治疗组给予DC-CIK联合化疗,对照组给予常规化疗。观察治疗前后细胞免疫指标变化、KPS和疗效,及不良反应。结果治疗组CD 3＋、CD 4＋免疫学指标治疗前后比较,具有显著性差异（P值分别为0.018,0.047）,而CD 8＋、CD 4＋/CD 8＋无显著性差异;对照组CD 3＋、CD 4＋、CD 8＋、CD 4＋/CD 8＋免疫学指标治疗前后比较,无显著性差异。治疗组有效率43.75%,对照组有效率34.38%（P〉0.05）。治疗组KPS有效率84.4%,对照组KPS有效率62.5%（P〈0.05）。结论 DC-CIK联合化疗可明显改善晚期NSCLC患者外周血淋巴细胞亚群水平,能增加患者的临床疗效,提高患者的生活质量。     

Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy

OBJECTIVE: Cytokine-induced killer (CIK) cells are ex vivo expanded cells enriched in CD3(+)CD56(+) natural killer T (NKT) cells with major histocompatibility-unrestricted cytotoxicity against several tumoral targets, except B-lineage acute lymphoblastic leukemia (B-ALL). We redirected CIK cells cytotoxicity toward B-ALL with a chimeric receptor specific for the CD19 antigen and then explored if modified-CIK cells maintain the same chemotactic properties of freshly isolated NKT cells, whose trafficking machinery reflects their preferential localization into the sites of B-ALL infiltration. MATERIAL AND METHODS: CIK cells were expanded ex vivo for 21 days and analyzed for expression of adhesion molecules and chemokine receptors regulating adhesion and homing toward leukemia-infiltrated tissues. CIK cells were then transduced with the anti-CD19-zeta-internal ribosomal entry site-green fluorescent protein retroviral vector and characterized for their cytotoxicity against B-ALL cells in a (51)Cr-release assay and for their trafficking properties, including chemotactic activity, adhesion and transendothelial migration, and metalloproteases-dependent invasion of Matrigel. RESULTS: Similarly to freshly isolated NKT cells, CD49d and CD11a were highly expressed on CIK cells. Moreover, CIK cells expressed CXCR4, CCR6, and CCR7 (mean expression 72%, 60%, and 32%, respectively), presenting chemotactic activity toward their respective ligands. Anti-CD19 chimeric receptor-modified CIK cells became cytotoxic against B-ALL cells (mean lysis, 60%) and showed, after exposure to a CXCL12 gradient, high capacity to adhere and transmigrate through endothelial cells and to invade Matrigel. CONCLUSION: The potential capacity to localize into leukemia-infiltrated tissues of anti-CD19 chimeric receptor-redirected CIK cells, together with their ability to efficiently kill B-ALL cells, suggests that modified-CIK cells represent a valuable tool for leukemia immunotherapy.     

Generation of CD3<Superscript>+</Superscript>CD56<Superscript>+</Superscript> Cytokine-Induced Killer Cells and Their In Vitro Cytotoxicity against Pediatric Cancer Cells

A certain number of pediatric cancer patients still succumb to relapse following conventional treatment of their malignancies. One of the mechanisms of relapse is escape from immunity. Adoptive cellular immunotherapy with effector cells has the potential to overcome this escape. In adults, the CD3+ CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. This effector cell type may work in children as well. No similar studies with children have been published. We speculated that expanded CD3+ CD56+ cells obtained from pediatric cancer patients during remission would act similarly against various pediatric tumor cell lines; therefore, we undertook the present study to find support for our speculation. This study was undertaken to generate and expand CD3+ CD56+ CIK cells from normal peripheral blood mononuclear cells (PBL) obtained from 6 children with cancer (2 with acute lymphoblastic leukemia, 2 with large cell lymphoma, and 2 with osteosarcoma) in remission after intensive chemotherapy and to study the cytotoxic activities of these cells against chronic myeloid leukemia cell line K562 t(9;22), 4 pediatric tumor cell lines [infant acute lymphoblastic leukemia RS4 t(4;11), TEL/AML acute lymphoblastic leukemia REH t(12;21), alveolar rhabdomyosarcoma Rh-Cr t(2;13), and Ewing sarcoma EW-Le t(11;22)], and 2 pediatric glioblastoma multiforme cultured cell lines (G74 and G77). CIK cells were generated and expanded in culture medium to which interferon gamma, monoclonal antibody against CD3, and interleukin 2 were added at appropriate times. Cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cell cytotoxicity against various pediatric tumor cell lines. The results show that after 21 days in culture CD3+ CD56+ CIK cells derived from the 6 pediatric patients accounted for a median of 28.3% of the entire culture (range, 10.7%-36.4%). Before expansion no such cells were found in any of the 6 children. Median lytic activity rates of CIK cells were 45.5% to 64.5%, rates that contrasted drastically to the lytic activity rates of PBL, which were only 8% to 12%. The findings of the present study are encouraging. They provide information for developing adoptive immunotherapy for future clinical trials with pediatric cancer patients, particularly those patients with minimal residual disease after intensive chemotherapy or stem cell transplantation (especially nonmyeloablative transplantation procedures).     

Intensive treatment and stem cell transplantation in chronic myelogenous leukemia: long-term follow-up

In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1-3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1-3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. approximately 60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.     

脐血来源或自体细胞因子诱导的杀伤细胞联合干扰素治疗慢性乙型肝炎的安全性和有效性分析

目的观察应用脐血和自体细胞因子诱导的杀伤细胞(CIK细胞)联合干扰素治疗慢性乙型肝炎(CHB)的安全性和有效性。方法 30例CHB患者均为解放军第一○五医院感染科2010年10月-2013年6月住院患者,签署临床实验研究入组同意书后随机分为3组,每组10例,治疗组分别给予脐血或自体CIK细胞移植,同时给予干扰素治疗,对照组仅接受干扰素治疗,观察治疗后4、12周患者外周血ALT、HBV血清学标志物(HBV M)、HBV DNA对数值和CD4+/CD8+水平的变化。两样本均数比较采用配对t检验或成组t检验。结果脐血或自体CIK细胞移植后12周,患者外周血ALT、HBeAg、HBV DNA对数值分别为(22.6±14.4)和(32.9±15.3)U/L;(12.5±5.8)和(18.4±8.8)PEIU/ml;(3.2±0.7)和(3.7±0.6),与对照组相比均明显降低(t=2.80~5.45,P0.05)。两治疗组治疗4周后CD4+和CD4+/CD8+水平均较对照组明显升高(t=2.21~2.43,P0.05);两组移植患者术中均未出现严重不良反应,无与移植相关的严重并发症发生。结论人脐血和自体CIK细胞移植治疗CHB,短期内可明显抑制病毒复制,改善患者肝功能和临床症状,并能提高患者细胞免疫水平,具有良好的安全性。     

T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications

Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post-AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients.     

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.     

Low curative potential of bone marrow transplantation for highly aggressive acute myelogenous leukemia with inversion inv (3)(q21q26) or homologous translocation t(3;3) (q21;q26)

Structural rearrangements of the long arm of chromosome 3 involving bands 3q21 and 3q26 and leading either to a paracentric inversion inv (3)(q21q26) or a translocation between both homologous chromosomes – t (3;3)(q21q26) – have been reported in patients with acute myelogenous leukemia (AML), myelodysplastic syndromes, myeloproliferative disorders, and chronic myelogenous leukemia in blast crisis. We describe three patients with de novo AML with these structural abnormalities who received multiple courses of conventional chemotherapy followed by unrelated donor (n=2) and autologous (n=1) bone marrow transplantation (BMT). All three patients had early relapse: patients 1 and 2 had relapse 69 days and 306 days after BMT, respectively, and patient 3 immediately after autologous BMT. Despite further chemotherapy, they died without achieving another remission. These findings, together with other recorded similar cases, show that AML with structural abnormalities of the long arm of chromosome 3 as described has an extremely poor prognosis even with the most potent anti-leukemic treatment modalities. Received: 30 June 1999 / Accepted: 14 December 1999     

Proliferation and cytolytic function of anti-CD3 + interleukin-2 stimulated peripheral blood mononuclear cells following bone marrow transplantation.

We evaluated the proliferation, cytolytic function, and phenotypic characteristics of anti-CD3 plus interleukin-2 (IL-2) stimulated peripheral blood mononuclear cells (PBMCs) from 44 patients with leukemia or non-Hodgkin's lymphoma (NHL) treated with multiagent chemotherapy or following bone marrow transplantation (BMT). BMT patients had decreased cell growth with only a 1.35 +/- 0.25 (autologous BMT for acute lymphoblastic leukemia [ALL]), 1.24 +/- 0.25 (autologous BMT for NHL), and 0.8 +/- 0.1 (allogeneic BMT for leukemia) mean fold increase by day 5 of culture compared with controls (4.0 +/- 0.4), P less than .001. Anti-CD3 + IL-2 activated cells from patients with ALL and NHL who had received autologous BMT and cells from patients with leukemia who underwent allogeneic BMT were more effective in lysing the natural killer (NK) sensitive target, K562, and the NK-resistant target, Daudi, compared with controls. In contrast, cytolysis of K562 and Daudi by cultured PBMCs from patients with ALL and NHL receiving multi-agent chemotherapy was similar to that of controls. Cultures from BMT recipients had a significant increase in CD16+ (autologous ALL 5.7 +/- 1.5%, P less than .01; autologous NHL 12.4 +/- 3.5%, P less than .001; allogeneic 14.3 +/- 2.9%, P less than .001) and CD56+ cells (autologous ALL 27.6 +/- 12.0%, P less than .01; autologous NHL 39.3 +/- 9.5%, P less than .001; allogeneic 42.7 +/- 7.4%, P less than .001) compared with controls (CD16+ 2.5 +/- 0.4%; CD56+ 6.9 +/- 0.9%). Stimulation of PBMCs with anti-CD3 + IL-2 is effective in generating cells with high cytolytic function post-BMT.