Early diagnosis and successful treatment of a patient with transfusion-associated GVHD with autologous peripheral blood progenitor cell transplantation

BACKGROUND: Transfusion-associated GVHD (TA-GVHD) is an uncommon complication of blood transfusion. Diagnosis of TA-GVHD is difficult, and it is usually rapidly fatal. There are few documented sur- vivors of TA-GVHD. CASE REPORT: A 61-year-old woman with chronic lymphocytic leukemia (CLL) was treated with fludarabine followed by combination chemotherapy and high-dose radioimmunotherapy and peripheral blood progenitor cell (PBPC) rescue. She was transfused with nonirradiated blood components at an outside hospital and presented 10 days later with rash, elevated liver enzymes, and progressive pancytopenia. Skin biopsy was consistent with GVHD, and HLA typing of lymphocytes from the patient demonstrated mixed chimerism. The patient was treated with solumedrol and cyclosporin A, followed by high-dose cyclophosphamide and antithymocyte globulin and autologous PBPC infusion. She had rapid engraftment, resolution of skin rash, and normalization of liver function abnormalities. She is in good health with normal blood counts and no evidence of CLL 34 months after transplantation. CONCLUSION: TA-GVHD occurs in the setting of an immunocompromised recipient receiving nonirradiated blood components. A typical presentation includes skin rash, liver function abnormalities, and pancytopenia. Demonstration of mixed chimerism by HLA typing facilitated diagnosis in this patient. High-dose immunosuppression, facilitated by the availability of autologous PBPCs, resulted in a successful outcome.     

Potential for transfusion-associated graft-versus-host disease due to apheresis platelets matched for HLA class I antigens

Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in immunocompetent recipients of nonirradiated cellular blood components from donors who are homozygous for an HLA haplotype shared with the patient. In these cases, donor lymphocytes have no antigens foreign to the recipient, and this similarity in HLA antigens appears important for the development of TA-GVHD. Experience with 65 patients receiving apheresis platelets matched for class I HLA antigens was reviewed to determine the incidence of such a transfusion among HLA- matched, unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the patient received lymphocytes from a donor exhibiting no antigens foreign to the recipient, but the patient had additional HLA-A or -B antigens not present on donor lymphocytes. Twenty-three percent (n = 15) of patients received at least one such transfusion. In addition, most patients were immunosuppressed as a result of their underlying disease or therapy, which may decrease the degree of antigen matching required to initiate TA-GVHD. Until the pathogenesis of this disease is better understood, it is recommended that the transfusion of an HLA-matched cellular blood component be considered a risk factor for the development of TA-GVHD regardless of the patient's immune status, and that all such blood components be irradiated.     

Microchimerism, GVHD, and tolerance in solid organ transplantation

The phenomenon of microchimerism and its relationship to long-term graft tolerance is an area of active study. The ability to establish a tolerant state has been enhanced with current immunosuppressive drugs and emerging therapies such as donor HPC infusions. An undesirable outcome of host-donor WBC interaction is GVHD. GVHD is a rare complication reported most frequently in liver transplantation. Two cases of GVHD reported in recipients of organs from donors homozygous for a shared HLA haplotype would support a policy of avoiding the use of these donors. TA-GVHD is very rare in solid organ transplant recipients, with only four published cases; only two had convincing supportive evidence and one of these had an underlying hematologic abnormality. These few cases do not support a policy of routine irradiation of cellular blood components for all solid organ transplant recipients. The use of donor HPC infusions to enhance chimerism and graft tolerance has increased the number of GVHD cases observed (usually mild) and decreased the severity and number of rejection episodes. The long-term effects of donor HPC infusions on graft survival is under investigation.     

Fatal erythroderma (suspected graft-versus-host disease) after cholecystectomy. Retrospective analysis

Fatal postoperative erythroderma (POE) developed in a 52-year-old woman with gallstones who underwent elective cholecystectomy. During surgery, she was transfused with 3 units of unirradiated packed red cells stored in the liquid state for at least 4 days after collection. The POE is believed to have been the result of transfusion-associated graft-versus-host disease (TA-GVHD). The diagnosis of GVHD was based upon the characteristic clinical picture and retrospective HLA typing. The implicated donor was homozygous for an HLA haplotype that appeared to be shared with the recipient: A24-CBL-Bw52-DR2-DRw52-DQw1, the most common haplotype in the Japanese population. This case raises the possibility that a transfusion of relatively fresh blood from a donor who has no HLA antigens incompatible with the recipient may result in GVHD in patients with no apparent immunoincompetence who are undergoing relatively minor surgery with no chemotherapy or radiation therapy.     

Allogeneic transplantation combining mobilized blood and bone marrow in patients with refractory hematologic malignancies

BACKGROUND: Mobilized blood stem cells have been used successfully in autologous transplant recipients to reduce the complications of pancytopenia due to dose-intensive chemotherapy. Reports of cytokine- mobilized blood progenitor cells in allogeneic transplant recipients are rare. STUDY DESIGN AND METHODS: This is a pilot trial of six patients. Patients with advanced hematologic malignancy received bone marrow (median total 2.6 × 10(8) mononuclear cells/kg) followed by four daily transfusions of blood (median total 9.5 × 10(8) mononuclear cells/kg) from HLA-matched sibling donors who were mobilized with recombinant human granulocyte-colony-stimulating factor (5 micrograms/kg/day subcutaneously for 5 days). All patients received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis. RESULTS: An absolute neutrophil count greater than 500 per mm3 was achieved on Day 12, and platelet transfusion independence was achieved on Day 16. The median day of hospital discharge was Day 23 after transplant. All patients achieved 100-percent donor cell engraftment. Acute > or = Grade III GVHD did not develop in any patients, but all patients developed Grade I (n = 4) or Grade II (n = 2) acute GVHD. Chronic extensive GVHD developed in four of six patients. One patient died of pneumonia 263 days after transplant while undergoing immune-suppressive therapy for chronic GVHD. CONCLUSION: The transfusion of blood stem cells in patients undergoing allogeneic bone marrow transplant is well tolerated soon after transplant, but the development of chronic GVHD may limit the general usage of unmanipulated blood stem cells.     

Fatal graft-versus-host disease associated with transfusions of HLA- matched, HLA-homozygous platelets from unrelated donors

BACKGROUND : Transfusion-associated graft-versus-host disease (TA-GVHD) due to blood from HLA-homozygous related and unrelated blood donors has been described. CASE REPORT: Fatal TA-GVHD due to the transfusion of HLA-matched platelets from an unrelated HLA-homozygous donor is reported. A 61-year-old man with a history of diabetes mellitus and myelodysplastic syndrome was diagnosed with acute myelogenous leukemia in November 1991. Induction chemotherapy resulted in aplasia, which was followed by a normocellular marrow with mild dysplasia and continued karyotypic abnormalities. High-dose chemotherapy was given in a second attempt to achieve complete remission. HLA-matched platelets were ordered when platelet refractoriness developed. The patient was HLA- heterozygous for HLA-A and -B antigens (A2, 29; B37, 44). Over the next 7 days, four unirradiated HLA-matched plateletpheresis units were transfused; one was probably homozygous for both HLA-A and -B antigens (A2, -; B44, -) and was transfused first, and three were probably homozygous for an HLA-B antigen (A2, 29; B44, -) and were white cell reduced. No blood relatives served as donors. Seven days after the first HLA-matched platelet transfusion, fever, chills, and diarrhea developed; 2 days later, a rash was present. Liver enzymes increased markedly. Renal and respiratory failure ensured. A skin biopsy was consistent with GVHD. Despite immunosuppressive therapy, the patient died 19 days after the first HLA-matched platelet transfusion. CONCLUSION : TA-GVHD has been recognized in immunocompromised, HLA- heterozygous patients receiving blood from blood relatives who are HLA- homozygous. patients receiving blood from either blood relatives or non- blood relatives who are HLA-homozygous. This HLA-heterozygous patient received transfusions of unirradiated, class I HLA-homozygous platelets, which were specifically ordered as HLA-matched, and his death was attributed to TA-GVHD. Consideration should always be given to providing irradiated blood for immunosuppressed patients, especially when HLA-matched platelets are used, to prevent TA-GVHD.     

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

Mini-transplantation from HLA-mismatched donors

Bone marrow transplantation(BMT) from genotypically human leukocyte antigen (HLA)-matched siblings improves long-term survival in patients with hematologic malignancies. However, more than 70% of patients who could benefit from allogeneic BMT do not have a matched sibling donor. Furthermore, allogeneic BMT has been limited to young patients because of the increased risk for regimen-related toxicity and graft-versus-host disease(GVHD) that occurs with increasing age. HLA-haploidentical minitransplantation may solve these problems. In minitransplants using a preconditioning regimen consisting of fludarabine, busulfan and anti-T-lymphocyte globulin and a GVHD prophylaxis of tacrolimus and methylprednisolone, we showed that minitransplantation from HLA-haploidentical related donors was possible.     

How is transfusion-associated graft-versus-host disease similar to,yet different from,organ transplantation-associated graft-versus-host disease?

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis.It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.     

FBC预处理方案在HLA半相合异基因外周血干细胞移植中的应用

目的　观察降低预处理强度对HLA半相合异基因干细胞植入的影响。方法　用氟达拉宾 (30mg m2 × 6d)、白消安 (4mg kg× 2d)、环磷酰胺 [(30～ 6 0 )mg kg× 2d]组成FBC方案。将 12例白血病患者分成两组 ,HLA完全相合移植组 4例 ,移植前患者处完全缓解状态 ;HLA半相合移植组 8例 ,皆为难治性白血病 ,其中 1例HLA 3个位点不合 ,6例二个位点不合 ,1例一个位点不合 ,接受本处理方案后 ,进行G CSF动员的异基因外周血干细胞移植 ,并于移植后第 30天 (+30天 )、+6 0天、+90天输注供者淋巴细胞 ,观察异基因干细胞植入和长期植入情况。结果　HLA半相合组患者平均接受 4.87× 10 8 kg供者外周血单个核细胞 ,其中CD3 4+细胞平均数为 4.5 8× 10 6 kg,HLA全相合组平均接受 4.85× 10 8 kg供者外周血单个核细胞 ,其中CD3 4+细胞 4.47× 10 6 kg。HLA半相合组 7例白细胞升至 1.0×10 9 L的平均时间为 2 9d(11～ 90d) ,血小板升至 2 0× 10 9 L的时间为 36d(14～ 96d) ,1例HLA 3个位点不合的患者移植失败 ,但该患者于 +5 0天恢复自体造血。而HLA全相合的 4例患者白细胞升至 1.0×10 9 L平均需 14d(11～ 18d) ,血小板升至 2 0× 10 9 L平均需 15d(11～ 18d)。经STR PCR检测 ,两组患者除 1例表现为混合嵌合体 ,其余均呈完     

HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血

目的 探索HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血的可行性.方法 16例Ⅲ度重型β地中海贫血患儿接受HLA单倍体相合外周血造血干细胞移植.预处理方案:2007年12月前采用A方案,即氟达拉滨(总量150 mg/m2)+白消安(静脉,总量520 mg/m2)+环磷酰胺(总量100 mg/kg)+抗胸腺细胞球蛋白(总量10 mg/kg)+全身照射(总量3 Gy);2007年12月后采用B方案,即氟达拉滨(总量240 mg/m2),不进行全身照射,其余同A方案.移植物抗宿主病(GVHD)预防采用环孢素+甲氨蝶呤+霉酚酸酯三联方案.结果 16例患者中14例(87.5％)成功植活,中性粒细胞≥0.5×109/L的时间为移植后第10～17天,中位时间第13天;血小板≥20×109/L的时间为移植后第14 ～20天,中位时间第15天.植活的14例患者移植后第30天检测证实均为供者型完全嵌合状态.2例患者未能植入,其中1例于移植后第52天自体造血恢复.Ⅱ～Ⅳ度急性GVHD4例,其中皮肤Ⅱ度GVHD2例,皮肤Ⅲ度GVHD1例,肠道Ⅳ度急性GVHD 1例,广泛型慢性GVHD1例.中位随访时间49个月,14例患者存活,其中13例无病存活.结论 HLA单倍体相合外周血造血干细胞移植治疗重型β地中海贫血,可以使多数患者获得长期稳定的植活,对于无全相合供者的患儿而言是一种可行的治疗选择,急慢性GVHD仍是影响长期生存率及生活质量的主要因素.     

Spontaneous resolution of transfusion-associated graft-versus-host disease

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood transfusion that is characterized by high fever, a scaly maculopapular erythematous rash, diarrhea, hepatocellular damage with marked elevation of liver function test values, and pancytopenia. It can occur in immunocompetent as well as immunocompromised recipients. The existence of atypical TA-GVHD that resolves spontaneously and does not exhibit all of the manifestations has been suggested, but there has been to date no documented diagnosis of GVHD supported by evidence of engraftment. CASE REPORT: A female patient presented and was diagnosed with acute myelogenous leukemia (AML:M4), and, after unsuccessful combination chemotherapy, she received a transfusion and developed manifestation of TA-GVHD as well as evidence of chimerism. TA-GVHD was proved by demonstrating Y chromosome-specific genes in the skin by polymerase chain reaction. The manifestations of clinical GVHD abated within 4 months. CONCLUSION: Polymerase chain reaction analysis of Y chromosomes in specimens from female patients is useful in the diagnosis of suspected cases of spontaneously resolving TA-GVHD.     

Universal or selective irradiation: a comparison of approaches

Pathological mechanisms proposed for transfusion-associated graft-versus-host diseases (TA-GVHD) include HLA homozygosity in donor cells of the transfusion unit that is shared by the recipient (one-way HLA match) and immunosuppression in the transfusion recipient. Which of these factors is indispensable or to what degree each factor contributes to the development of TA-GVHD has been the issue of debate. In countries like Japan with higher HLA homogeneity, TA-GVHD occurrence was thought to be primarily dependent on the one-way HLA match mechanism regardless of immunosuppression. Accordingly, universal irradiation of blood components has been conducted with no further TA-GVHD cases. In other developed countries, in contrast, TA-GVHD was thought to be a sort of extrapolation of GVHD observed among heavily immunosuppressed patients. Guidelines with the detailed list of diseases with the indication for irradiated components have been established in those countries. Although TA-GVHD occurrence decreased markedly after the introduction of universal leukoreduction, a considerable number of TA-GVHD cases have occurred among immunocompetent patients mostly by the one-way HLA match mechanism. Because one-way HLA matching with donor homozygosity is thought to be a ubiquitous and independent mechanism for TA-GVHD, it could occur in any transfusion setting regardless of immunosuppression. It would be thoughtful to select an area-specific strategy considering the drawbacks of irradiation and the frequency of TA-GVHD in that area. However, if complete abolition of TA-GVHD is required from the perspective of the high fatality of the disorder, universal irradiation of cellular components will be necessary.     

Transfusion‐associated graft‐versus‐host disease in a liver transplant recipient: an unusual presentation and review of the literature

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a rare, nearly universally fatal complication from transfusion of nonirradiated cellular blood components, occurring when a recipient's immune system is unable to recognize and destroy transfused T lymphocytes. Irradiation of cellular components eliminates this risk. We present an unusual case of a liver transplant recipient developing TA‐GVHD 13 weeks after transfusion of a random unit of nonirradiated red blood cells (RBCs) that happened to be from a donor homozygous for an HLA haplotype shared by the patient. STUDY DESIGN AND METHODS: This study was a single case review of a liver transplant recipient who developed skin GVHD and marrow aplasia. Clinical course and the chimerism studies involving the patient, the liver donor, and the blood donor are detailed. RESULTS: The patient presented 3 months posttransplant with GVHD of his skin and marrow aplasia. In addition to standard antigraft immunosuppression, this patient had started the interleukin‐1 receptor antagonist anakinra on Posttransplant Day 13 for an acute gout flare. Chimerism studies on the patient's peripheral blood identified a population of CD3 cells that did not originate with either the patient or his liver donor. HLA studies and microsatellite profiling of the unknown CD3 population identified the source of the patient's TA‐GVHD, a unit of nonirradiated, nonleukoreduced apheresis RBCs. CONCLUSION: Use of an immunomodulating agent may have contributed to the development of TA‐GVHD in a liver transplant patient who received a random unit of nonirradiated RBCs by chance from an unrelated haploidentical donor.     

Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) is a fatal complication of transfusion of blood products that usually affects immunocompromised patients. Articles reporting this condition in immunocompetent recipients are usually from countries that still have problems in irradiation of blood products. CASE REPORTS: This report presents fatal TA-GVHD in four immunocompetent patients referred from rural areas where blood irradiation is still not the routine procedure to our tertiary-care center between July 2004 and July 2005. A similar history and chronological order of events were observed: fresh whole-blood transfusion from relatives, fever, rash, liver dysfunction, diarrhea, and pancytopenia. Skin biopsies demonstrated Grade II to III GVHD involvement. Marrow biopsies showed hypoplasia. In two cases, HLA typing studies were performed. Donors were homozygous for a shared HLA haplotype in the patients. All cases were admitted to the intensive care unit within 3 weeks after transfusions with the diagnosis of sepsis, which rapidly progressed to septic shock and multiorgan failure. Another common observation was Candida albicans growth in blood cultures. Unfortunately, all died despite prompt and appropriate sepsis treatment, along with immunomodulatory therapy. CONCLUSION: TA-GVHD is probably more prevalent than reported in the literature. It must be considered in the differential diagnosis, if the patient with a recent transfusion history admits with fever, skin rash, abnormal liver function tests, and pancytopenia associated with hypoplastic marrow. In rural areas where gamma irradiation is not possible, the overall policy of transfusion (e.g., restriction of transfusion indications and alternative methods for pathogen inactivation) should be reassessed.     

Transfusion-associated GVHD: 10 years' experience at the American University of Beirut-Medical Center

BACKGROUND: Although rare, transfusion-associated GVHD (TA-GVHD) is a fatal complication of blood transfusion in which active lymphocytes from the donor attack and destroy recipient organs and tissues. STUDY DESIGN AND METHODS: A search of patient records was carried out at the American University of Beirut-Medical Center, looking for patients who developed TA-GVHD over a 10-year period extending from 1991 to 2001. Relevant information was collected and analyzed. RESULTS: A total of 10 records were found as a result of this search. All were immunocompetent and received fresh nonleukoreduced, nonirradiated blood. The majority received the transfusion at outside periphery hospitals. They received different treatment modalities. The mortality rate was 100 percent. CONCLUSION: TA-GVHD is a serious complication with very high mortality. Effective prevention guidelines should be established in Lebanon including irradiation and the creation of a central blood bank.     

The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion-associated graft-versus-host disease

BACKGROUND: The pathogenesis of posttransfusion purpura (PTP) and transfusion-associated graft-versus-host disease (TA-GVHD) involves patient exposure to donor platelets (PLTs) and T lymphocytes, respectively, which are removed during blood component leukodepletion (LD). STUDY DESIGN AND METHODS: Reports of PTP and TA-GVHD to the UK hemovigilance scheme Serious Hazards of Transfusion (SHOT) from 1996 to 2005 were compared before and after implementation of universal LD during 1999. RESULTS: There were 45 reports of PTP, with a mean of 10.3 per year before universal LD and 2.3 per year afterward (p < 0.001). All patients had received red cells, but before universal LD, only 1 of 31 (3%) cases had also received PLTs, compared to 8 of 14 (57%) afterward (p < 0.001). Thirty-four cases (76%) had human platelet antigen (HPA)-1a antibodies, whereas 11 had antibodies to other HPA specificities, only 1 of which occurred after LD. Two cases reported before LD also had heparin-dependent PLT antibodies. There were 13 reports of TA-GVHD, all fatal, of which only 2 cases of undiagnosed immunodeficiency met current UK criteria for irradiated components. Eight others had one or more risk factors: B-cell malignancy (6), steroids (1), fresh blood (1), and donor-recipient HLA haplotype share (4). Eleven cases were due to non-LD and 2 to LD components (p < 0.001). No cases have been reported since 2001. In an additional 405 cases, nonirradiated components were transfused in error to high-risk recipients, mainly on fludarabine, but none developed TA-GVHD. CONCLUSIONS: These findings suggest that universal LD has further reduced the already low risk of TA-GVHD in immunocompetent recipients and has altered the profile of PTP cases.     

Transfusion-associated graft-versus-host disease in a presumably immunocompetent patient after transfusion of stored packed red cells

A 54-year-old woman developed transfusion-associated graft-versus-host disease (TA-GVHD) after the transfusion of stored packed red cells obtained from unrelated donors. The patient was presumed to be immunocompetent. A diagnosis of TA-GVHD was made by clinical features and postmortem pathologic findings. Sex chromatin analysis of the patient's lymphocytes demonstrated chimerism. HLA typing of the blood donors revealed one to be HLA-homozygous for one of the patient's HLA haplotypes (A33-B44-Cblank). This case illustrates the risk in the general patient population of TA-GVHD after routine blood transfusion therapy. Workers should be aware of this possibility and should continue searching for an efficient way to prevent it.     

异基因造血干细胞移植治疗自体造血干细胞移植后复发的非霍奇金淋巴瘤临床观察

目的 探讨对自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)后复发的非霍奇金淋巴瘤患者再进行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-...     

非清髓异基因造血干细胞移植治疗血液病多中心临床报告

目的 研究观察我国多中心非清髓异基因造血干细胞移植(NST)治疗血液病的疗效和相关并发症.方法 我国NST协作组9个中心共243例血缘相关HLA相合的血液病患者接受了NST治疗.在FAC[氟达拉滨(Flud)、抗胸腺细胞球蛋白(ATG)和环磷酰胺(CTX)]非清髓预处理方案的基础上加用阿糖胞苷或白消安等.移植物抗宿主病(GVHD)预防采用环孢素(CsA)联合霉酚酸酯(MMF)方案.结果 移植后4周供体完全植入163例(67.1%),移植失败2例(0.8%),混合植入78例(32.1%),其中56例移植后1～16个月转为完全植入,16例维持混合嵌合(MC)状态,6例移植排斥.83例(34.2%)发生急性GVHD,其中Ⅰ～Ⅱ度26例(28.9%),Ⅲ～Ⅳ度16例(6.6%);慢性GVHD 78例(32.1%).随访3～99个月,243例中仍存活162例(66.7%),其中骨髓增生异常综合征/再生障碍性贫血、慢性白血病、急性白血病首次完全缓解(CR1)和难治复发急性白血病患者的5年预期存活率分别为76.5%、73.9%、70.7%和27.8%.243例中46例(18.9%)移植后疾病复发或移植排斥.58例急性白血病CR1患者中白血病复发率为17.2%,36例难治复发急性白血病复发率为50%.结论 以FAC为基础的非清髓预处理方案有较好的耐受性和造血恢复作用,供体植入可靠,重度GVHD减少,总体生存率较高,为血液病的治疗提供了新途径.