自体外周血干细胞加激活骨髓联合移植治疗T细胞淋巴瘤的诱导移植物抗宿主病

目的 研究自体造血干细胞( APBSC)加激活骨髓(ABM)联合移植治疗淋巴瘤过程中ABM诱导移植物抗宿主病(GVHD)的作用。方法一例T免疫母细胞非霍奇金淋巴瘤(NHL)患者行APBSC+ABM联合移植治疗，观察皮疹、腹泻及黄疸的发生。结果皮肤出现Ⅰ～Ⅱ度GVHD改变，无腹泻及黄疸，已无瘤生存13年。结论APBSC加ABM联合移植能诱导GVHD，并获得长期无病生存的疗效。     

急性髓系白血病自体造血干细胞移植后长期生存并正常生育三例

目的 探讨造血干细胞移植(HSCT)对患者生育功能的影响.方法 回3例接受自体造血干细胞移植(auto-HSCT)后长期生存并正常生育的急性髓系白血病(AML)患者的临床资料,并复习相关文献.结果 3例AML患者中,女1例,男2例,接受不含全身放疗预处理方案的auto-HSCT,分别在停止治疗后68、65和65个月生育一健康小孩.结论 育龄期接受HSCT患者的生育问题在制定治疗方案时应引起重视.     

CAG方案治疗低增生性急性髓系白血病29例

目的 观察CAG方案治疗低增生性急性髓系白血病(AML)的临床疗效.方法 对29例低增生性AML患者采用CAG方案,阿柔比星(Acla)14 mg/m2,第1天至第4天,静脉注射;阿糖胞苷(Ara-C)10 mg/m2,第1天至第14天,每12 h皮下注射;粒细胞集落刺激因子(G-CSF)200μg/m2,第1天至第14天,皮下注射,并于第1次注射Ara-C之前12 h开始使用,最后一次注射Ara-C前12 h停用;当中性粒细胞＞10×109/L时,暂时减少或停用G-CSF.结果 29例患者中完全缓解(CR)14例(48.3%),部分缓解(PR)7例(24.1%),总有效率72.4%,治疗失败(NR)7例,早期死亡1例.结论 CAG方案治疗低增生性AML安全有效,可有效缩短外周血粒细胞减少的时间,降低化疗相关死亡率.     

急性白血病造血干细胞移植后胸壁粒细胞肉瘤复发一例并文献复习

目的 观察急性白血病造血干细胞移植(HSCT)后孤立性胸壁粒细胞肉瘤(GS)复发的临床特点.方法 回顾性分析1例急性髓系白血病(AML)患者异基因HSCT(allo-HSCT)后3年并发孤立性胸壁GS的临床资料.结果 患者胸部CT发现心膈角处肿物,经手术发现肿物原发于胸壁,切除后病理诊断为GS,经化疗以及局部放疗后治愈,目前无复发迹象,仍在定期随访中.结论 化疗联合局部放疗是治疗髓外孤立性GS的较好的方法,对于AML-HSCT的患者,需要注意髓外复发病灶的检测.     

慢性粒细胞白血病治疗新进展:第52届美国血液学年会热点

慢性粒细胞白血病(chronic myelogenous leukemia,CML)是一种起源于造血干细胞的恶性增殖性疾病,以9号和22号染色体异位形成费城染色体(Ph)为特征,该异位形成一种新的bcr-abl融合基因,此基因编码的融合型蛋白能导致髓系造血的异常克隆性增殖.     

骨髓间充质干细胞治疗慢性移植物抗宿主病后患者外周血T细胞受体V β亚家族谱系变化研究

目的 研究输注骨髓间充质干细胞(MSC)治疗慢性移植物抗宿主病(cGVHD)后患者外周血T细胞受体(TCR)Vβ基因谱系变化及克隆性增殖情况.方法 1例经异基因造血干细胞移植(allo-HSCT)后发生cGVHD的患者接受MSC治疗,分别于第1次输注MSC后第1、5天及第2次输注MSC后第1、10、20天采集外周血,同时将输注的MSC作为对照,利用反转录-聚合酶链反应(RT-PCR)方法扩增单个核细胞中24个TCR V β基因的互补决定区3(CDR3),PCR产物经荧光标记和基因扫描分析CDR3长度,从而确定T细胞的克隆性.结果 患者输注的MSC不表达全部TCR V β亚家族,第1次输注MSC后第1天也未发现TCR Vβ亚家族的表达,随后的时间点分别出现了3、10、14、10个Vβ亚家族的克隆增殖T细胞,增殖形式以寡克隆、多克隆为主;临床判断cGVHD表现减轻.结论 MSC对allo-HSCT后患者免疫功能的恢复有一定作用,并能减轻cGVHD效应;TCR V β亚家族谱系分析提示有部分优势表达.     

非血缘脐血造血干细胞移植的现状

脐血是骨髓和外周血干细胞以外的新的干细胞主要来源,脐血移植特别是非血缘脐血移植( UCBT)的数量逐年增加。UCBT存在的主要问题在于脐血的造血干/祖细胞(HSC/HPC)数量少,可能导致植入延迟或植入失败。临床上采用多种方法来提高脐血HSC/HPC的数量,包括双份脐血输注、减低强度的预处理、体内体外扩增脐血细胞、同时输注单倍体血缘供者CD34+细胞或间充质干细胞( MSC)、或将脐血细胞直接注入骨髓等,取得了良好的疗效。UCBT将会成为更多患者的治疗选择。     

小剂量阿糖胞苷姑息治疗65岁以上老年人急性髓系白血病32例

目的 分析小剂量阿糖胞苷(Ara-C)治疗65岁以上老年人急性髓系白血病(AML)的临床疗效.方法 回顾性分析32例65岁以上老年AML患者的临床资料,包括基础疾病、主要症状、临床特征、骨髓象、外周血、染色体、免疫分型、应用小剂量Ara-C化疗效果等.Ara-C 15 mg/m2,皮下注射,2次/d.结果 32例老年患者中,完全缓解(CR)3例(93%),部分缓解(PR)19例(58.3%),总有效率68.6%;FLT3-ITD阳性的患者疗效差,有染色体复杂异位的患者疗效差.结论 小剂量Ara-C姑息性治疗65岁以上AML患者有一定疗效,在一定程度上可以提高患者的生活质量,延长生存期.     

中剂量依托泊苷联合粒细胞集落刺激因子动员恶性淋巴瘤的外周血造血干/祖细胞

目的 观察中剂量依托泊苷(VP16)和粒细胞集落刺激因子(G-CSF)在恶性淋巴瘤患者动员采集自体外周血造血干/祖细胞的有效性和安全性.方法 31例恶性淋巴瘤患者(非霍奇金淋巴瘤30例,霍奇金淋巴瘤1例),VP16 1.2 g/m2分3 d静脉滴注,外周血白细胞降至最低点时给予G-CSF每天5μg/kg,分2次,皮下注射,直至采集结束.结果 VP16应用后12 d(10～15 d)开始采集外周血造血干/祖细胞,获得单个核细胞(MNC)7.8×108/kg[(5.2～11.3)×108/kg],CD+34细胞7.2×106/kg[(5.3～13.1)×106/kg] 18例患者采集1次,13例采集2次.所有患者移植后均恢复造血,外周血粒细胞＞0.5×109/L的中位时间为12 d(9～18 d),血小板＞20×109/L的中位时间为14d(10～21 d).患者无严重不良反应结论中剂量VP16和G-CSF动员恶性淋巴瘤患者外周血干/祖细胞有效、安全,可获得满意的动员采集效果.     

间充质干细胞在造血干细胞移植中的应用

间充质干细胞是一种能够从各种人成体组织分离出来的非造血多能干细胞,近年来,许多研究表明间充质干细胞具有免疫调节能力及促进组织重建等功能.就其在造血干细胞移植中的应用,如急慢性移植物抗宿主病(GVHD)、GVHD造成的移植失败、纯红细胞再生障碍性贫血及免疫性血小板减少性紫癜、出血性膀胱炎作以综述.     

High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma

BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation (autoSCT) induces complete remissions in the majority of patients with advanced B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma (B-CLL). However, the long-term utility of this therapy for B-CLL is unknown. PATIENTS AND METHODS: Sixteen previously treated patients with B-CLL were transplanted using autologous blood (n = 13) or bone marrow (n = 3). The median age of the patients was 49 f1p4s (range 44-60 years), and the median number of prior chemotherapy regimens was two. Patients were eligible for transplantation if they had chemosensitive disease and no morphologic evidence of malignant cells in the graft. Preparative regimens included cyclophosphamide and total-body-irradiation, with or without cytarabine, or BEAC. RESULTS: All patients engrafted and achieved a complete remission posttransplant. Ten patients were alive at a median of 41 months (range 22-125 months), and five were disease-free. Eight patients have relapsed and six have died (three from progressive malignancy). The projected three-year overall survival, failure-free survival and relapse rates were 68%, 37%, and 56%, respectively. CONCLUSIONS: AutoSCT for advanced B-CLL is associated with a high relapse rate. Whether this therapy can prolong life or produce cures is uncertain.     

Autologous bone marrow transplant in acute myeloid leukemia in first remission

PURPOSE: The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival. PATIENTS AND METHODS: After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused. RESULTS: Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years. CONCLUSION: Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.     

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children

The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.     

Allogeneic stem cell transplantation for advanced low-grade lymphoproliferative disorders: report of six cases

BACKGROUND: Allogeneic stem cell transplantation is being increasingly used to treat young patients with poor-prognosis low-grade lymphoproliferative disorders. We report our single-center experience. PATIENTS AND METHODS: Six adults (four with advanced chronic lymphocytic leukemia, one follicular center cell lymphoma and one mantle cell lymphoma) underwent allogeneic stem cell transplantation (SCT). Five received bone marrow while one received peripheral blood stem cells. Donors were HLA-identical siblings in five cases and an HLA-haploidentical sibling in one. The conditioning regimen included in five cases cyclophosphamide, TB1 and high-dose chlorambucil, without the latter in the patient with follicular lymphoma. RESULTS: Five patients successfully engrafted, while the patient who received the haploidentical marrow suffered primary graft failure. There were two cases of grade 2 acute GVHD and one limited chronic GVHD. Four patients are alive in complete remission (CR) with a follow-up of 17+ to 118+ months. Additionally, there is no evidence of residual disease by immunologic and molecular techniques in three cases, while one patient has residual disease assessed by molecular methods. CONCLUSIONS: These results suggest that allogeneic SCT can achieve prolonged remissions in advanced chronic lymphoproliferative disorders.     

Peripheral blood progenitor cell mobilization with Dexa-Beam/G-CSF, ether lipid purging, and autologous transplantation after high-dose CBV treatment: a safe and effective regimen in patients with poor risk malignant lymphomas

High-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation (PBPCT) is increasingly applied in patients with relapsed, poor risk malignant lymphomas. Different strategies for progenitor cell mobilization using cytoreductive chemotherapy, hematopoietic growth factors, or both have been described. We studied the safety and efficacy of a modified DexaBEAM regimen (dexamethasone, BCNU [carmustine], etoposide, ara-C, melphalan) followed by granulocyte-colony stimulating factor (G-CSF) that was administered in order to minimize any residual disease and to obtain a sufficient amount of progenitor cells in the autografts. Until now, 16 patients at poor risk (8 with Hodgkin's disease, 8 with non-Hodgkin's lymphoma) entered the study. All the 12 patients with measurable disease at study entry responded to DexaBEAM. Median time of subsequent leukopenia (leukocytes < 1.000/microL) was 6 days (range 5-8 days). Peak numbers of CD34+ hematopoietic progenitor cells appeared in the peripheral blood after a median of 20 days (range 18-22 days) after onset of therapy. At that time, peripheral mononuclear cells were collected for autografting. Thereafter, the leukapheresis products were frozen until the day of transplantation, either unpurged in the case of Hodgkin's disease or purged with the ether lipid edelfosine in cases of non-Hodgkin's lymphoma. After high-dose chemotherapy with the CBV regimen (cyclophosphamide, BCNU, etoposide) the patients received their autografts, followed again by G-CSF treatment. A stable hematopoietic recovery was reached with granulocytes > 2.000/muL within 11 days (range 8-17 days), and platelets > 50.000/microL within 15 days (range 10-31 days), respectively, without significant differences between the purged and unpurged transplants. After a median follow-up of 28 months (range 1-40 months) 7 patients are alive without signs of recurrent disease, while 1 patient has died due to acute treatment related toxicity. Three patients had refractory disease, and 5 have relapsed of whom 4 have died. In summary, the DexaBEAM/G-CSF/CBV strategy appears to be safe and effective for salvage treatment in patients with poor risk malignant lymphomas.     

Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in Type 1 diabetic patients with elevated urinary albumin excretion

BACKGROUND: Immunoablative high-dose cyclophosphamide without stem-cell rescue induces durable, complete remission in most patients with aplastic anemia. OBJECTIVE: To determine the efficacy of high-dose cyclophosphamide in various refractory, severe autoimmune diseases. DESIGN: Prospective phase II study. SETTING: Johns Hopkins University (Baltimore, Maryland) and Hahnemann University (Philadelphia, Pennsylvania). PATIENTS: Eight patients with refractory, severe autoimmune disease. Intervention: Immunoablative high-dose cyclophosphamide (50 mg/kg of body weight per day) for 4 consecutive days. MEASUREMENTS: Clinical and laboratory variables of autoimmune disease. RESULTS: Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continuous complete remission for 3 to 21 months, and two patients in partial remission continue to improve after 14 and 19 months of follow-up. High-dose cyclophosphamide was well tolerated; median times to a neutrophil count of 0.5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days, respectively. CONCLUSIONS: Immunoablative high-dose cyclophosphamide without stem-cell rescue can induce complete remission in patients with refractory, severe autoimmune disease. Reemergence of marrow function is similar to that seen after autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.     

Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma

PURPOSE: To determine the incidence, natural history, and risk factors associated with myelodysplastic syndrome (MDS) occurring as a late complication following autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma. METHODS: We retrospectively reviewed the charts of all 262 patients who underwent autologous bone marrow transplantation for non-Hodgkin's lymphoma at the Dana-Farber Cancer Institute from 1982 through 1991. Although patients received a variety of treatments before they were eligible for transplant, identical myeloablative therapy (cyclophosphamide 60 mg/kg/d for 2 days plus total-body irradiation twice daily for 3 days) was administered in each case. By collecting data on pretransplant and early posttransplant variables, we attempted to identify risk factors for the development of MDS. RESULTS: The crude overall incidence of posttransplant MDS or acute myeloid leukemia (AML) was 7.6%. The actuarial risk at 6 years was 18% +/- 9%. The median time of onset was 31 months (range, 10 to 101) after transplant or 69 months (range, 27 to 141) after initial treatment for lymphoma. Pretreatment variables predictive for the development of MDS (univariate analysis) included prolonged interval between initial treatment and the transplant procedure (P = .003), increased duration of exposure to chemotherapy (P = .019) or to alkylating agents (P = .045), and use of radiation therapy (P = .032) or pelvic radiation (P = .003) before transplant. CONCLUSION: MDS is a potential complication of autologous bone marrow transplantation for non-Hodgkin's lymphoma; bone marrow stem-cell damage sustained before the transplant may be the most important risk factor.     

Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum

Patients who undergo transplantation with haploidentical "three-loci" mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from HLA-haploidentical "three-loci" incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E-rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.     

Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer

Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retroviral vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer.     

Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.