Transplantation For Severe Aplastic Anemia Research Articles

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study.

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40years of age and older. With a median follow-up time of 17.6months, 85 consecutive patients were enrolled in the study, and the median patient age was 45years (40, 58). Thecumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9±0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3years were 14.1±0.1% and 17.3±0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2±3.2% and 89.7±3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7±6.4% for HID vs 92.1%±4.4% for MSD and 100% for URD, P=.481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40years and older without a matched donor.

Population Frequency of Fanconi Pathway Gene Variants and Their Association with Survival After Hematopoietic Cell Transplantation for Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is most frequently immune-mediated; however, rare inherited bone marrow failure syndromes, such as Fanconi anemia (FA), may be causal and can present as aplastic anemia (AA). FA is primarily an autosomal recessive disorder caused by the presence of 2 pathogenic variants in a single FA/BRCA DNA repair pathway gene. Patients with SAA often undergo genetic testing during clinical evaluation that may identify single deleterious alleles in FA pathway genes. We quantified the rate of germline single deleterious alleles in 22 FA genes using both a general population database (3234 variants, 125,748 exomes) and in a cohort of patients with SAA undergoing hematopoietic cell transplantation (HCT) (21 variants in 730 patients). The variants were classified as deleterious using in silico tools (REVEL, MetaSVM, VEP) and database resources (ClinVar, LOVD-FA). We found similar rates of single deleterious alleles in FA genes in both groups (2.6% and 2.9%). The presence of a single deleterious variant in a gene for FA in SAA HCT recipients did not affect the overall survival after HCT (hazard ratio, 0.85; 95% CI, 0.37 to 1.95; P =0.71), or post-HCT cancer risk (P = 0.52). Our results demonstrate that the identification of a germline monoallelic deleterious variant in an FA gene in patients with idiopathic SAA does not influence the outcome of HCT. Our findings suggest that there is no need for special treatment considerations for patients with SAA and a single deleterious FA allele identified on genetic testing.

Impact of ABO incompatibility on outcomes after haploidentical hematopoietic stem cell transplantation for severe aplastic anemia.

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.

Real-world outcomes of stem cell transplantation for severe aplastic anemia: A single-center experience in Northern India.

Stem cell transplantation is the cornerstone of therapy for transplant-eligible patients with severe aplastic anemia. Patients with severe aplastic anemia undergoing stem cell transplantation (including matched haplo-identical related donors) with a standard conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were analyzed. High-risk patients were identified as having undergone >20 pre-transplant transfusions, having febrile neutropenia at the time of transplantation, or having undergone failed immunosuppressive therapy. A total of 111 patients underwent stem cell transplantation, with a median age of 17 years. Seventy-six patients received matched related donor (MRD) transplants, and 35 received haplo-identical donor (HID) transplants. Among all patients, 65.7% were high-risk patients, with a significantly higher proportion among those receiving HID transplants (38% for MRD vs. 83% for HID). Acute GVHD grades 2-4 was observed in 9% of patients, and chronic GVHD in 16.2% of patients. Primary graft rejection was more common in 9.9% of patients (21% for HID, 5% for MRD). The 2-year overall survival and disease-free survival were 67% and 66%, respectively, with better outcomes for MRD and low-risk HID transplants than for high-risk HID transplants. The most common cause of mortality was sepsis-related death (accounting for 27% of the total deaths). Sepsis-related early deaths were significantly more common among high-risk patients who received HID transplants. We conclude that MRDs remain the preferred donor source for allogeneic stem cell transplants in patients with aplastic anemia; however, HIDs can be considered as a life-saving treatment for patients with aplastic anemia.

Relapse of Aplastic Anemia with Majority Donor Chimerism (Donor-Type Aplasia) Occurring Late after Bone Marrow Transplantation.

There have been sporadic reports of the development of delayed disease recurrence after bone marrow transplantation for severe aplastic anemia despite sustained majority or full donor chimerism. This is termed "donor-type aplasia" (DTA). We describe the management and outcome of 11 pediatric patients from 8 institutions in Europe, the United States, and the Middle East who developed DTA at a mean of 35 months post-transplant. These patients were initially transplanted at a mean age of 10.0 years (range, 5.8 to 16.0 years), 9 from matched sibling donors and 2 from matched unrelated donors. Attempts to treat DTA with varying combinations of additional immunosuppression (including intravenous immunoglobulin, donor lymphocyte infusions, stem cell boosts, and other therapies) failed. Ten patients have received a conditioned second transplant, 9 from the same donor and 1 from a new matched unrelated donor. Aplasia has resolved in the remaining patient in response to ongoing eltrombopag therapy. All patients were alive at a mean of 92 months (range, 26 to 195) after a second transplant; 6 are in complete remission, but 4 suffered from second/recurrent DTA at 16 to 129 months after retransplant and required further transplant therapy.

Clinical analysis of the timing and efficacy of allogeneic stem cell transplantation for severe aplastic anemia with infections

Clinical analysis of the timing and efficacy of allogeneic stem cell transplantation for severe aplastic anemia with infections

Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia

AbstractAllogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

Aplastic Anemia Preconditioned with Fludarabine, Cyclophosphamide, and Anti-Thymocyte Globulin.

BackgroundGraft rejection and graft versus host disease (GvHD) have impeded the success of hematopoietic cell transplantation for severe aplastic anemia (SAA) patients. There is no sufficient data to identify the outcomes of peripheral blood stem cell transplantation (PBSCT) in SAA patients, especially for adult SAA patients. The aim of this study was to evaluate the outcomes of adult SAA patients undergoing PBSCT with the FCA regimen. The FCA regimen includes fludarabine, cyclophosphamide, and anti-thymocyte globulin (ATG).Material/MethodsWe report our experience with 46 adult SAA patients who underwent PBSCT with the FCA regimen. Thirty SAA patients who received only cyclophosphamide and ATG (CA) regimen were used as controls. Complications and survival outcomes were evaluated and compared.ResultsThere was a significantly higher percentage of patients who achieved >95% donor chimerism by day 30 in the FCA group. The 5-year event-free survival (EFS) rate in the FCA group was higher than that in the CA group (95.4% versus 73.3%). In addition, the 5-year rejection rate (RR) in the FCA group was lower than that in the CA group (4.6% versus 23.6%). A multivariable model identified the FCA regimen as an independent factor affecting EFS and RR. However, GvHD and serious infection did not differ between the 2 groups. For patients with an unrelated donor, the FCA regimen had a higher EFS and a lower RR than the CA regimen.ConclusionsThe FCA regimen for PBSCT in adult SAA patients compared favorably to the CA regimen. It can improve EFS and reduce graft rejection, especially for unrelated donor PBSCT.

PB1855 UPFRONT HAPLOIDENTICAL TRANSPLANT IN YOUNG SEVERE APLASTIC ANEMIA PATIENTS ‐ RESULTS OF A PILOT STUDY FROM SOUTH INDIA

Background:Haploidentical bone marrow transplant is one of the second line treatment option in severe aplastic anemia patients failing immunosuppressive therapy. In younger patients, allogeneic bone marrow transplant from a matched sibling donor gives more than 80% long‐term remission rates. But unfortunately, only 30% patients will have a matched sibling donor. In a middle‐income country like India, the availability and affordability of patients to an unrelated donor is limited. Most of our patients have got a single chance for treatment and many relapsed patients go into palliative care.Aims:Aim of the present study is to evaluate the efficacy and safety of upfront Haploidentical bone marrow transplant in less than 40 years old severe aplastic anemia patients not having a 10/10 matched donor.Methods:This is a prospective non‐randomized single center study conducted during the period from January 2017 to June 2018. Eleven patients less than 40 years old underwent upfront Haploidentical bone marrow transplantation for severe aplastic anemia during the above period. Peripheral blood stem cell was used in all patients.FLU‐ATG‐PTcy was the conditioning regimen used in all patients with Cyclosporine + MMF based GVHD prophylaxis. This study got clearance from institutional review board and the transplant was sponsored by government.Results:In six patient's donors were parents (Mother in four and father in two) and rest of the donors were siblings. Two were Fanconi positive and none had a PNH clone. Seven were 5/10 matched, three were 6/10 and one was 7/10 matched. All patients had engraftment at a median of 11 days (range 8 to 13 days). One patient had fatal grade IV acute GVHD and succumbed to GVHD on day +36. Seven patients (64%) had grade I/II GVHD and three patients (27%) had grade III GVHD. 64% patients had grade I/II chronic GVHD at date cut off of January 2019. 10 patients (89%) attained complete remission and were alive till January 2019.The overall survival rate at one year post transplant was around 89% which is better than immuno‐supressive therapy in this age group. No differnces were observed in engraftment dates or survival outcomes based on type of donor and degree of mismatch. The study patients are very small to get statistically significant rates.Summary/Conclusion:With nearly 90% overall remission and survival rate at one year, upfront haploidentical transplant seems to be a safe and effective option in young patients with severe aplastic anemia. This will help to reduce the cost of Matched unrelated donor stem cells significantly in resource poor countries and increase the number of patients opting for a curative treatment.

Co-Transplantation of Mesenchymal Stem Cells Can Ameliorates Acute Gvhd and Viremia after Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia: A Multi-Center Retrospective Study of 119 Patients

Abstract BACKGROUD:Mesenchymal stem cells (MSCs) are known to exhibit immunomodulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (AA). OBJECTIVE: To explore the efficacy and safety of allo-HSCT by co-transplantation with MSCs in AA patients. METHODS: We conducted a multi-center retrospective study to comparing the incidence and severity of acute GvHD, transplant-related complication and overall survival (OS) of allo-HSCT with or without co-injection of MSCs in AA patients. A total of 119 consecutive severe AA patients (64 males/55 females) undergoing allo-HSCT at 4 hospitals from January 2012 to February 2018 were analyzed. The median age of the patients is 23 (range 1-56 years). Patients received conditioning regimens based on cyclophosphamide or busulfan, among whom 50 (42%) were MSD-HSCT, 21(17.6%) MUD-HSCT and 48 (40.4%) haplo-HSCT. All patients received cyclosporine A with short course methotrexate for prevention of GVHD. 89 patients transplanted with donor HSCs only, and 30 patients transplanted with HSCs and MSCs .MSCs infusion dose was 0.5-3.0×106/kg, at -1~+1 days following HSCs infusion. None of these patients had severe infection or organ failure before HSCT. RESULTS: The two groups were well matched demographically. All patients achieved successful engraftment within one month post transplant. There was no difference in time to leukocyte and platelet engraftment in the two groups. The incidence of aGVHD grade II-IV (7.9 % versus 6.7 %, P =1.000) was similar in the HSC versus MSC groups, but there was a trend to a lower incidence of aGVHD grade III-IV in the MSC group (3.4% versus 0%, P=1.0). Moreover, a lower incidence of viremia in the MSC group was observed (CMV: 26.7% vs 62.9%, P &lt; 0.001; EBV: 50% vs 80.9%, P = 0.002).With a median follow-up time of 811 days (range:28-2348days),the 2-yr OS was similar in both groups (82.8% versus 71.1%, P =0.498). A combination of bone marrow and peripheral blood as the sources of stem cells co-transplanted with MSCs (n=9) demonstrated an improved survival benefit (2-yr OS=100%). CONCLUSION: Co-transplantation with MSCs could ameliorate the challenges of aGVHD and viremia and facilitate survival in allo-HSCT for AA patients. Disclosures No relevant conflicts of interest to declare.

Combined haploidentical and umbilical cord blood transplantation for severe aplastic anemia: Unique hematopoietic reconstitution

Abstract Hematopoietic stem cell transplant (HSCT) with matched sibling donor (MSD) is considered the first line of therapy for patients with severe aplastic anemia (SAA) who are

Blastic Epstein-Barr virus associated post-transplant lymphoproliferative disorder after allogeneic stem cell transplantation for severe aplastic anemia.

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. Progress has recently been made in the pathological classification of PTLD. However, the clinical course has not been clarified because of the rarity of this disease. We experienced a case of PTLD with a fulminant clinical course. The patient had been under longterm immunosuppressive treatment for aplastic anemia. He received related allogeneic hematopoietic stem cell transplantation. Soon after transplantation, he developed PTLD. According to the guidelines, we reduced immunosuppression. However, the disease course was so fulminant that there was no time for the patient to respond, and he died of multi-organ failure. There may be various clinical types of PTLD, which may include some fulminant cases. In such a case, it is not sufficient to reduce immunosuppression. The patient should be carefully observed and an appropriate individual treatment should be chosen.

Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation Achieved Outcomes Comparable With Matched Unrelated Donor Transplantation in Young Acquired Severe Aplastic Anemia

Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P = .001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P = .045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P = .129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P = .198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P = .210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P = .127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P = .976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA.

Late chimerical status after bone marrow transplantation in severe aplastic anemia according to two different preparatory regimens

BackgroundThis study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. MethodsPatients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n=55) received 200mg/kg cyclophosphamide alone and Group II (n=49) received 120mg/kg cyclophosphamide associated with 12mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. ResultsChimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51–90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value<0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value=0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value<0.001) and higher number of infused cells (p-value=0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value=0.003) and platelet counts (p-value<0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. ConclusionThese data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.

136 - Outcomes of a Novel Rituximab-Based Non-Ablative Conditioning Regimen for Hematopoietic Cell Transplantation in Severe Aplastic Anemia

136 - Outcomes of a Novel Rituximab-Based Non-Ablative Conditioning Regimen for Hematopoietic Cell Transplantation in Severe Aplastic Anemia

Clinical efficacy and safety of porcine antihuman lymphocyte immunoglobulin in alternative donor allogeneic hematopoietic cell transplantation for severe aplastic anemia

目的比较预处理方案含猪抗人淋巴细胞免疫球蛋白（pALG）或兔抗人胸腺细胞免疫球蛋白（rATG）替代供者异基因造血干细胞移植（AD allo-HSCT）治疗重型再生障碍性贫血（SAA）患者的疗效及安全性。方法回顾性分析2006年1月至2016年11月46例接受AD allo-HSCT SAA患者的临床资料，按预处理方案包含rATG或pALG分为两组，比较两组植入率、移植相关并发症发生率及转归。结果rATG组30例患者均获得粒细胞植入，27例患者获得血小板植入。pALG组16例患者粒细胞及血小板均植入。两组患者在移植后急性移植物抗宿主病（aGVHD）（P=0.475）、Ⅲ~Ⅳ度aGVHD（P=0.876）、慢性移植物抗宿主病（cGVHD）（P=0.309）、广泛型cGVHD（P=0.687）、移植物排斥（GR）（P=0.928）、血流感染（P=0.443）、侵袭性真菌病（P=0.829）、巨细胞病毒血症（P=0.095）发生率方面差异均无统计学意义。rATG组中位随访14（2~102）个月，预期5年总生存率为（75.1±8.2）%；pALG组中位随访23（4~63）个月，预期5年总生存率为（53.6±13.3）%，差异无统计学意义（P=0.190）。结论SAA患者行AD allo-HSCT，预处理方案应用pALG可取得与rATG相近疗效，且并不增加GVHD、GR及感染等移植后并发症的发生率。

Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor–mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m2 [MTX15] and 10 mg/m2 [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.

Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia

目的探讨重型再生障碍性贫血（SAA）患者行异基因造血干细胞移植（allo-HSCT）后发生植入功能不良（PGF）的危险因素。方法回顾性分析111例行allo-HSCT的SAA患者临床资料及移植情况，采用Cox比例风险模型对可能影响PGF的因素进行单因素及多因素分析。结果在111例行allo-HSCT的SAA患者中，共有16例发生了PGF（14.4%）。多因素分析结果显示，非血缘供者（HR＝2.656，95%CI 1.204～5.858，P＝0.016）及移植前血清铁蛋白浓度（SF）>1 000 µg/L（HR＝3.170，95%CI 1.400～7.180，P＝0.006）是发生PGF的独立危险因素。结论非血缘供者及移植前SF>1 000 µg/L的患者移植后容易发生PGF。

Improved outcome by optimized conditioning regimens with an increased dose of cyclophosphamide in allogeneic peripheral blood stem cell transplantation for severe aplastic anemia

目的分析减量环磷酰胺（Cy）的联合预处理方案对接受同胞全相合外周血造血干细胞移植（MSD-PBSCT）的重型再生障碍性贫血（SAA）患者疗效的影响。方法51例获得性SAA患者接受MSD-PBSCT，预处理方案含两种减量Cy（150 mg/kg或120 mg/kg）联合氟达拉滨（Flu）和抗胸腺细胞球蛋白（ATG）。比较两组患者生存率、植入情况、移植物抗宿主病（GVHD）和感染发生率间的差异。结果预处理含150 mg/kg Cy组（Cy150组）患者与含120 mg/kg Cy组（Cy120组）比较，5年总生存与无失败生存率相近（93.5%对90.0%，χ2=0.170，P=0.680；90.3%对85.0%，χ2=0.285，P=0.594）。但是多因素分析结果显示，Cy120组急性GVHD（HR=3.89，95% CI 1.21~12.53, P=0.023）及慢性GVHD（HR=4.48，95% CI 1.40~14.32，P=0.011）发生风险均显著高于Cy150组。而两组间的机会性感染发生率及移植排斥率差异均无统计学意义。结论与120 mg/kg相比，150 mg/kg的Cy联合Flu和ATG的预处理方案更能改善接受MSD-PBSCT治疗的获得性SAA患者的总体疗效。

Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning.

Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy).A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS).All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age <15 years, MNC cells >8×108/kg and donor age <45 years were associated with better survival (P=0.043, P=0.023, and P=0.037, respectively) and engraftment (P=0.019, P=0.008, and P=0.001, respectively).Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.