Allogeneic hematopoietic cell transplantation (allo-HSCT) is an essential therapeutic modality hematological malignancies, but acute graft-versus-host disease (aGvHD) persists as a leading cause of non-relapse mortality (NRM) . Cytokine biomarkers have already been used to predict aGvHD and outcomes. However, the standard guidelines for aGvHD biomarker panels remain controversial. We retrospectively analyzed the association of a biomarker panel (suppressor of tumorigenesis 2 [ST2], regenerating islet-derived 3 α [REG3α], Elafin, and tumor necrosis factor 1 [TNFR1]) in serum with the onset of 100-day aGvHD, 12-month NRM, and overall survival (OS) in 141 hematological malignancies patients at 19 ± 5 days after allo-HSCT from January 2022 to August 2023. Multivariable analysis showed that ST2 (P < .001) were strongly correlated with aGvHD, and TNFR1 was significantly associated with 12-month NRM and OS (P < .001). The panel of ST2, REG3α, Elafin, and TNFR1 demonstrated the best performance in diagnosis of 100-day aGvHD (area under the curve [AUC] = 0.79) and in the prediction of 12-month NRM (AUC = 0.74) and OS (AUC = 0.71). The 4-biomarker panel's risk classification predicted the 12-month cumulative incidence of NRM (43% vs 11%, P < .001) and 12-month OS (51% vs 82%, P < .001) for the high-risk and low-risk groups, respectively. Our results suggest that a combination of ST2, REG3α, Elafin, and TNFR1 is an excellent biomarker predictive panel for aGvHD diagnosis and outcomes after allo-HSCT.
Graft failure (GF) is a barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelofibrosis (MF). We investigated the incidence, risk factors, and prognosis for GF after allo-HSCT for MF. Two hundred and eleven patients with MF who underwent allo-HSCT across 32 hematology centers in China between December 2008 and December 2024 were retrospectively analyzed. Among them, 66 underwent matched sibling donor HSCT, 127 haploidentical HSCT, and 18 unrelated donor HSCT. The overall GF incidence was 12.5%. GF incidence was significantly associated with donor type (matched sibling, 4.8%; alternative, 13.3%; P = 0.024). Pretransplant massive splenomegaly increased GF incidence (non-massive splenomegaly, 8.5%; massive, 18.5%; P = 0.034). In multivariate analysis, massive splenomegaly (HR = 3.047; P = 0.007) and alternative donors (HR = 3.528; P = 0.041) increased GF risk. With median follow-up of 734 days, 3-year OS, DFS, relapse rate and NRM was 65.5%, 60.8%, 10.1% and 27.8%, respectively. Multivariate analysis showed pretransplant splenomegaly reduced 3-year DFS (HR = 1.671; P = 0.025), and alternative donors reduced 3-year OS (HR = 2.033; P = 0.015). In conclusion, Allo-HSCT provides curative outcomes for MF patients. However, GF remains a significant challenge, particularly in haploidentical HSCT and those with massive pretransplant splenomegaly.
Background and Significance Total Body Irradiation (TBI) is a key component of conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in acute leukemia patients with extramedullary infiltration. However, its clinical application is limited by acute and long-term toxicities caused by whole-body radiation. Total marrow and lymphoid irradiation (TMLI), with its advantages of high target conformity and superior organ-at-risk sparing, has emerged as a potential alternative. Nevertheless, its efficacy and recurrence risk in high-risk patients with extramedullary lesions remain unclear. This study compares the efficacy and safety of TMLI versus TBI in this population to inform clinical conditioning regimen selection. Key Findings In acute leukemia patients with extramedullary lesions, TMLI and TBI showed comparable hematopoietic reconstitution and incidence of acute graft-versus-host disease (aGVHD). However, the TMLI group had a lower incidence and later onset of cytomegalovirus (CMV) infection. There was no statistically significant difference in overall survival outcomes between the two groups, but TMLI demonstrated an advantage in overall survival (OS) in the acute lymphoblastic leukemia (ALL) subgroup, especially in ALL patients with pre-transplant bone marrow remission. Age ≥30 years and pre-transplant bone marrow non-remission were identified as independent risk factors for poor prognosis in the TMLI group. Methods and Results This was a single-center retrospective cohort study, enrolling 91 patients with acute leukemia who underwent allo-HSCT between January 2019 and December 2023 and had extramedullary lesions before transplantation or during the disease course. Patients were divided into the TMLI group (32 cases) and TBI group (59 cases) based on conditioning radiotherapy modality. The TMLI group received 12Gy in 3 fractions, while the TBI group received 12Gy in 6 fractions; both groups were combined with myeloablative chemotherapy. The primary endpoint was 3-year OS, and secondary endpoints included engraftment, CMV infection, aGVHD, disease-free survival (DFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). Patient Baseline: The two groups were balanced in terms of age, gender and pre-transplant bone marrow status, with a significant difference only in disease distribution (TMLI: 53.1% ALL vs. TBI: 61.0% Acute Myeloid Leukemia (AML); p=0.009). Engraftment & aGVHD: There was no significant difference in neutrophil engraftment (median time: 13.5 vs 13.0 days, p=0.405) or platelet engraftment (14.0 vs 15.0 days, p=0.665) between the two groups. The 100-day cumulative incidence of aGVHD (47.5% vs 41.1%, p=0.512) and grade Ⅱ-Ⅳ aGVHD (31.0% vs 17.3%, p=0.181) also showed no statistical differences. CMV Infection: The TBI group had a higher 100-day cumulative incidence of CMV infection (71.9% vs 57.7%, p=0.046) and an earlier onset of infection (median: 39.0 vs 57.0 days, p=0.030). Survival Analysis: With a median follow-up of 341 days, there were no statistically significant differences between the TMLI and TBI groups in 3-year OS (64.4% vs 45.7%, p=0.183), DFS (48.3% vs 39.7%, p=0.547), CIR (32.4% vs 26.1%, p=0.734), or NRM (19.2% vs 29.9%, p=0.245). Subgroup Analysis: In the ALL subgroup, the TMLI group showed a trend toward improved 3-year OS (88.2% vs 57.1%, p=0.062) and DFS (76.5% vs 50.6%, p=0.093). Notably, in ALL patients with pre-transplant bone marrow remission, the TMLI group had significantly higher 3-year OS (100% vs 64.2%, p=0.034). No differences in survival outcomes were observed in the AML subgroup. Risk Factors: Multivariate analysis in the TMLI group revealed that age ≥30 years (OS: HR=7.42, p=0.031; DFS: HR=4.65, p=0.012; CIR: HR=7.68, p=0.007) and pre-transplant bone marrow non-remission (CIR: HR=5.28, p=0.040) were independent risk factors for adverse prognosis. Conclusion TMLI demonstrates a favorable safety profile with a lower risk of CMV infection in allo-HSCT for acute leukemia with extramedullary lesions and shows potential survival benefits in the ALL subgroup, particularly among those with pre-transplant bone marrow remission. TMLI efficacy in AML requires validation through dose optimization (e.g., increasing TMLI dose). Age and pre-transplant bone marrow status are critical for TMLI patient prognosis assessment.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for relapsed/refractory acute leukemia (R/R AL), but outcomes remain suboptimal due to lack of standardized conditioning regimens. Intensive conditioning with chemotherapy (CLAG/FLAG) combined with radiotherapy (total body irradiation [TBI]/total marrow lymphoid irradiation [TMLI]) may improve efficacy, but comparative data are limited.We retrospectively analyzed 233 R/R AL patients (2015–2023) who underwent allo-HSCT with conditioning regimens of radiotherapy (TBI/TMLI) combined with CLAG or FLAG. Patients were grouped as: TBI/CLAG (n=139), TMLI/CLAG (n=21), TBI/FLAG (n=59), TMLI/FLAG (n=4). Disease subtypes included AML (n=180, 80.7%) and ALL (n=43, 19.3%). Most patients were not in remission at transplant (n=184, 82.5%); remitted patients (n=39, 17.5%) all had extramedullary disease. The last follow-up date was May 1, 2025. Primary endpoints: overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM).For the entire cohort, 10-year outcomes were: OS 32.9% (95%CI 27.0–40.0%), DFS 29.6% (95%CI 23.9–36.6%), CIR 34.5% (95%CI 28.2–40.8%), and NRM 35.3% (95%CI 29.0–41.6%). No statistically significant differences in OS, DFS, CIR, or NRM were observed between radiotherapy+CLAG vs. radiotherapy+FLAG (all P>0.05). Subgroup analyses in AML and ALL (stratified by TBI-based regimens) also showed no significant differences in these endpoints. However, in ALL patients, TBI/CLAG trended toward better 5-year OS (56.6% vs. 36.7%, P=0.081) and lower 5-year NRM (18.2% vs. 44.4%, P=0.097) compared to TBI/FLAG. Conclusion: Intensive conditioning with CLAG/FLAG combined with radiotherapy is effective and well-tolerated in R/R AL patients undergoing allo-HSCT. TBI/CLAG may confer superior survival outcomes in ALL, warranting further validation in larger cohorts.
Objective:To investigate the clinical and molecular features of patients with CD7 +relapsed or refractory acute myeloid leukemia(r/rAML)and the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods:172 r/rAML patients who underwent allo-HSCT in department of hematology, Aerospace Center Hospital between January 1st 2017 and December 31st 2020 were retrospectively analyzed The patients were were divided into CD7 + group( n=75) and CD7 - group( n=97) according to the expression CD7 in the initial immunophenotype. Mann-Whitney U and Chi-square test were used to compare the clinical data, molecular and cytogenetic characteristics of the two groups of patients. Kaplan-Meier method was used to analyze the median progression-free survival (PFS) and median overall survival (OS) of the two groups of patients, and Cox regression screenthe prognostic factors of the patients. Results:The median follow-up time was 19 months. The recurrence rates were 23.71% and 50.67%, respectively in CD7 - and CD7 + group (χ 2=13.428 P<0.001). In relapsed patients, 86.96 percentage of CD7 - group did not express CD7 while 86.84 percentage of CD7 + group expressed CD7. The median PFS was 25 and 5 months in CD7 - and CD7 + group (χ 2=8.695, P=0.003), and the medianOS was 34 and 15 months in CD7 - and CD7 + group (χ 2=2.579, P=0.108). Univariate analysis showed that the CD7 +group, had the lower rates of morphological remission (χ 2=10.014, P=0.002), molecular remission (χ 2=22.809, P<0.001), and more male patients (χ 2=5.281, P=0.022). The incidence of CEBPA double-site mutation was higher (23.4% vs 8.2%, χ 2=8.180, P=0.004) and the rearrangement of RUNX1::RUNX1T1 was lower(4.0% vs18.6%, χ 2=8.362, P=0.004)in CD7 +group than in CD7 -group. Multivariate analysis showed that pre-transplant tumor load was the only prognostic factor for PFS (HR, 1.600; 95% CI, 1.203 to 2.127; P=0.001) and OS (HR, 1.737; 95% CI, 1.273 to 2.369; P<0.001) in r/r AML patients. Conclusion:CD7 expression is a risk factor for poor prognosis in r/r AML patients, and CD7 expression is stable after relapse. Positive CD7 can be used as a target for immune targeted therapy.
Refractory or relapsed acute myeloid leukemia (R/R AML) remains the major challenge of AML treatment. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only valid option to achieve cure, but the prognosis is still dismal. We conducted a retrospective analysis for the feasibility of CLAG regimens (cladribine, cytarabine, and granulocyte colony-stimulating factor) combined with total body irradiation (TBI) as new intensive conditioning chemotherapy prior to HSCT in R/R AML. A total of 70 patients, including 21 primary refractory and 49 relapsed AML, were analyzed. Forty-nine (70
Abstract Background Acute myeloid leukemia (AML) patients with a Fms‐like tyrosine kinase 3 (FLT3) mutation have a high incidence of relapse despite allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and a subsequent poor prognosis. FLT3 inhibitors (FLT3i) have been suggested to reduce the post‐transplant relapse risk in recent studies. As more evidence is accumulated, we perform the present meta‐analysis to assess the efficacy and safety of FLT3i as post‐transplant maintenance therapy in AML patients. Methods Literature search was performed in public databases from inception to December 31, 2021. Overall survival (OS), relapse‐free survival (RFS), cumulative incidence of relapse (CIR), non‐relapse mortality (NRM), graft‐versus‐host disease (GVHD) and adverse events were compared between FLT3i and control groups. Pooled hazard ratio (HR) or relative risk (RR) with corresponding 95% confidence interval (CI) were calculated. Results We identified 12 eligible studies with 2282 FLT3‐mutated AML patients who had received HSCT. There was no between‐study heterogeneity and a fix‐effect model was used. Post‐transplant FLT3i maintenance significantly prolonged OS (HR = 0.41, 95%CI: 0.32–0.52, p < 0.001) and RFS (HR = 0.39, 95%CI 0.31–0.50, p < 0.001), and reduced CIR (HR = 0.31, 95%CI 0.20–0.46, p < 0.001) as compared with control. There were no significant risk differences in NRM (RR = 0.69, 95%CI 0.41–1.17, p = 0.169), acute GVHD (RR = 1.17, 95%CI 0.93–1.47, p = 0.175), chronic GVHD (RR = 1.31, 95%CI 0.91–1.39, p = 0.276) and grade ≥3 adverse events between both groups, except for skin toxicity (RR = 5.86, 95%CI 1.34–25.57, p = 0.019). Conclusion Post‐transplant FLT3i maintenance can improve survival and reduce relapse in FLT3‐mutated AML patients and is tolerable.
目的 研究不同来源[血浆、痰液、支气管肺泡灌洗液(BALF)]标本的巨细胞病毒(CMV)DNA定量检测对异基因造血干细胞移植后CMV肺炎的诊断价值.方法 回顾性分析接受异基因造血干细胞移植的405例受者的临床资料,其中诊断为CMV肺炎的19例受者设为CMV肺炎组,选择同期仅发生CMV血症的229例受者、接受纤维支气管镜镜检的11例非CMV肺炎受者及根据病原学证据确诊细菌或真菌性肺炎进行痰培养的16例受者,分别设为对照A、B、C组.总结CMV肺炎的发生情况;分析CMV肺炎受者不同来源(血浆、痰液、BALF)标本的CMV DNA载量;总结CMV肺炎受者的预后情况.结果 405例异基因造血干细胞移植受者中有19例发生了CMV肺炎,CMV肺炎总体发生率为4.7%(19/405).CMV肺炎受者的血浆、痰液、BALF的CMV DNA载量均分别高于对照A、B、C组(均为P<0.05).19例受者中,有12例经抗病毒治疗后治愈,7例治疗失败死亡(其中3例放弃治疗),病死率为37%(7/19).结论 血浆、痰液、BALF的CMV DNA定量检测可提高CMV肺炎的诊断率,从而改善异基因造血干细胞移植受者的预后.
目的 探讨含全身放疗预处理方案与含白消安预处理方案治疗复发/难治急性髓系白血病的疗效对比.方法 回顾分析航天中心医院2012年5月至2017年12月进行异基因造血干细胞移植的135例复发/难治的急性髓系白血病,其中69例接受清髓的全身放疗方案(TBI-MAC)预处理,66例接受清髓的白消安方案(BU-MAC)预处理.对两组患者移植后合并症及复发率、非复发死亡率、无病生存率及总生存率进行比较.结果 中位随访时间为20(4~68)个月.两组患者移植后急、慢性移植物抗宿主病(GVHD)的发生率差异无统计学意义(P>0.05),巨细胞病毒和EB病毒的发生率差异无统计学意义(P>0.05).移植后2 a复发率TBI-MAC组为(47.7±7.1)%、BU-MAC组为(46.9±9.3)%;非复发死亡率TBI-MAC组为(25.0±6.3)%,BU-MAC组为(22.4±6.0)%,两组间比较,差异无统计学意义(P>0.05);无病生存率TBI-MAC组为(41.1±6.0)%,BU-MAC组为(38.5±6.6)%;总生存率TBI-MAC组为(42.3±6.1)%,BU-MAC组为(42.2±7.0)%,两组间比较,差异无统计学意义(P>0.05).结论 含全身放疗清髓预处理方案可以作为复发/难治急性髓系白血病AML的一个替代治疗方案.
目的 提高对造血干细胞移植患者合并镰刀菌感染,尤其是播散性镰刀菌病的认识,以做到早期诊断、及时治疗,从而改善其预后.方法 对本院从2015年4月至2020年9月诊治的4例造血干细胞移植患者合并播散性镰刀菌病的诊断、治疗及预后进行回顾性分析.结果 4例患者均为确诊病例,均发生于造血干细胞植活前或粒缺期,给予两性霉素B脂质体/两性霉素B联合伏立康唑抗真菌治疗.3例患者的播散性镰刀菌病得到控制(其中1例死于铜绿假单胞菌败血症),1例抗真菌治疗后无效死亡.结论 造血干细胞移植后播散性镰刀菌病预后差,死亡率高,早期给予有效抗真菌治疗及快速免疫重建是改善其生存率的有效手段.
Objective:To investigate the efficacy of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia associated with 11q23/MLL.Methods:Retrospection and analysis 50 cases of acute myeloid leukemia with 11q23/MLL and who were treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT)in our hospital from September 2012 to December 2019. The efficacy was evaluated by analyzing the transplantation success rate, graft-versus-host disease rate, infection rate, transplant-related mortality(TRM), accumulative recurrence rate, disease-free survival rate(DFS), and overall survival rate(OS).Results:Except for 1 patient had an unsuccessful stem cell transplantationas the result of multiple organ failure, the remaining 49 patients were successfully transplanted. The median time of leukocyte transplantation was 15(9~18)days, and the median time of platelet transplantation was 13(8~33)days. Bone marrow was assessed 28 days after transplantation, and 49 patients were in CR status. The median follow-up time was 38(3~79)months. Between remission group and non-remission group after transplantation, the 3-year OS rates were(83.3±10.8)%, (30.9+ 8.2)%( P=0.002)and the 3-year DFS rates were(83.3+ 10.8)%, (28.4±8.0)%( P=0.003), respectively. Conclusions:Allogeneic hematopoietic stem cell transplantation is an effective method for the treatment of 11q23/MLL rearranged AML. Patients in remission before transplantation have a higher survival rate, and recurrence after transplantation is the primary problem currently faced.
Objective:To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on therapy-related leukemia (TRL).Methods:The clinical data of 14 patients with TRL who received allo-HSCT in Aerospace Central Hospital from April 2012 to February 2020 were retrospectively analyzed, and the therapeutic efficacy and survival status were also analyzed.Results:Of the 14 patients, 5 were males and 9 were females; the median age was 35 years old (12-59 years old). There were 12 patients with acute myeloid leukemia, 1 patient with chronic lymphocytic leukemia/small cell lymphoma, and 1 patient with acute lymphoblastic leukemia. At the time of transplantation, 4 patients achieved bone marrow complete remission, 3 patients achieved bone marrow partial remission, and the remaining 7 patients had no remission. Five patients received HLA-matched sibling transplantation, 9 patients received haplotype transplantation, and they all received myeloablative pretreatment schemes. All 14 patients were successfully implanted; the median engraftment time of granulocyte was 16 d (10-24 d), and the median engraftment time of platelet was 13 d (10-34 d). Grade Ⅰ-Ⅱ acute graft-versus-host disease (GVHD) occurred in 7 patients, chronic GVHD occurred in 6 patients, and grade Ⅲ intestinal GVHD occurred in 2 patients. The median follow-up time was 32 months (4-97 months). Among 14 patients, 5 patients died.Conclusion:The allo-HSCT can improve the prognosis and long-term survival rate of TRL patients.
目的:评估旁系异基因造血干细胞移植(allo-HSCT)治疗急性白血病的疗效.方法:回顾性分析2012-07-01-2019-12-31接受旁系allo-HSCT的28例急性白血病患者的临床资料,其中男女各14例,中位年龄30(12~47)岁;急性髓系白血病19例,急性淋巴细胞白血病4例,急性混合细胞白血病2例,慢性髓系白血病急变期3例;表亲供者20例,堂亲供者8例;采用TBI联合CLAG预处理方案13例,采用CLAG联合改良BUCY预处理方案15例.结果:1例患者因感染性休克死于细胞未植活期,其余27例患者中性粒细胞、血小板中位植活时间分别为16(10~28)d、18(11~80)d.急性移植物抗宿主病累计发生率为(42.9±2.5)%,慢性移植物抗宿主病累计发生率为(21.3±10.5)%.其中17例发生CMV血症,4例发生EBV血症,8例发生出血性膀胱炎.中位随访时间11.5(1~95)个月,存活11例,移植后2年总生存(OS)率、无白血病生存(LFS)率分别为(37.8±9.5)%、(68.6±11.1)%,其中表亲为供者移植后2年OS率及LFS率分别为(28.6±10.6)%、(59.5±14.8)%,堂亲为供者移植后2年OS率及LFS率分别为(60.0±18.2)%、(85.7±13.2)%.2组生存分析采用Log-rank检验发现,OS率及LFS率比较差异均无统计学意义(P=0.150、0.403).Cox多因素分析提示,移植前疾病状态、HLA相合程度为影响患者OS[HR=6.268(95%CI 4.636~11.346),P=0.012;HR=5.668(95%CI 1.410~22.776),P=0.015]及LFS[HR=8.054(95%CI 0.987~65.688),P=0.051;HR=4.340(95%CI 1.183~15.926),P=0.027]的独立预后不良因素.结论:旁系供者可以作为急性白血病allo-HSCT供者,移植前疾病状态及HLA相合程度是旁系移植的独立预后不良因素.
目的:分析单份脐带血干细胞移植治疗成人难治复发性急性白血病的风险因素.方法:回顾性分析行单份脐带血移植治疗的18例难治复发急性白血病患者的临床资料,对其脐血移植经过及疾病转归进行分析.结果:18例(男10,女8)患者,中位年龄32(9 ~59)岁,中位体重65(36 ~101)kg.急性髓系白血病15例(其中骨髓增生异常综合征转化3例),T-急性淋巴细胞白血病2例,Ph+急性淋巴细胞白血病1例,形态学完全缓解5例,但其中1例伴有髓外病灶,余13例均未获得骨髓缓解.回输脐血有核细胞中位数2.23(1.01 ~3.27)×10 7/kg(受者体重),CD34+细胞中位数为0.92(0.37~4.92)×105/kg(受者体重),移植后42 d髓系累计植入率为83%,中位植入时间20(15 ~35)d,移植后120 d血小板累计植入率为83%,中位植入时间47.5(14~150)d.16例患者发生植入前综合征(PES),PES累计发生率为88%.3例未获得中性粒细胞植入,其中2例于+8d及+10d死于败血症及PES-多脏器功能衰竭,另1例+10d死于PES-肺泡出血,这3例患者均出现细胞因子风暴,血清IL-6水平>1 000 pg/mL.移植后1年移植相关死亡5例(30.8±11.7)%,累计复发死亡2例(13.3±8.8)%.完成植入的15例患者,移植后1年总生存11例(72±12)%,无病生存10例(61.7±14)%.结论:单份脐带血治疗成人白血病,可以成功植入;对于难治复发的急性成人白血病患者,是一种可以考虑的治疗方法.移植前骨髓原始细胞比例及PES是影响预后的主要因素.
目的 探讨含去甲氧柔红霉素(IDA)的预处理方案在异基因造血干细胞移植(allo-HSCT)治疗高危难治性白血病中的临床疗效.方法 对116例接受了allo-HSCT的高危难治性白血病患者,采用7种含IDA的预处理方案.总结116例受者的植入情况.采用Kaplan-Meier曲线对2年总生存率(OS)、2年无病生存率(DFS)、累积复发率、复发病死率、移植相关病死率(TRM)、急性移植物抗宿主疾病(aGVHD)及慢性移植物抗宿主疾病(cGVHD)的累积发生率进行统计学分析.结果 116例受者均成功植入.中位随访时间为28(7~70)个月,64例受者存活,2年OS为55.2%,2年DFS为51.7%,2年复发病死率23.3%,2年TRM为18.1%.116例受者中有72例发生aGVHD,aGVHD 2年累积发生率为62.1%,其中Ⅲ~Ⅳ度aGVHD20例,2年累积发生率为17.2%.59例发生cGVHD,2年累积发生率为55.4%,其中广泛型cGVHD2年累积发生率为14.7%.116例受者中有30例复发,2年累积复发率为25.9%.结论 含IDA的预处理方案安全性和有效性均较高,可以作为高危难治性白血病患者移植预处理的有效方案.
Objective To explore the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory or relapsed leukemia patients undergoing total body irradiation and FLAG regimen consisting of fludarabine,cytarabine,granulocyte colony stimulating factor (TBI/FLAG).Methods Forty-seven cases of refractory or relapsed leukemia treated in our hospital between May 2012 and December 2015 were analyzed retrospectively,including 14 cases of acute lymphoblastic leukemia,31 cases of acute myeloid leukemia,2 cases of acute transformation of chronic myelocytic leukemia.All patients did not achieve remission before bone marrow transplantation.The proportion of blast cells was 10%-98%.The TBI/FLAG was the main conditioning regimen.Kaplan-meier curve was used to analyze the cumulative incidence of GVHD,cumulative recurrence rate,overall survival rate (OS) and disease-free survival rate (DFS).Results Of 47 cases,there was only one patient with infection during the preconditioning and the cell engraftment was not successful,and the rest 46 patients were successfully engrafted.The median time of leukocyte engraftment was 17 (11-25) days,and the median time of platelet engraftment was 21 (11-70) days.The cumulative incidence of acute GVHD was (62.3 ± 7.3)%,including 51.1% and 28.4% in Ⅱ and Ⅲ-Ⅳ grade respectively.Twenty-four patients suffered chronic GVHD in 44 assessable patients,and the cumulative incidence was (77.1 ± 11.2)%.The bone marrow was assessed 28 days after transplantation,and the results showed that 46 patients achieved complete remission,and DNA test confirmed complete donor chimerism.The median follow-up time was 12 (1-44) months,25 patients survived (53.19%,25/47),and 13 relapsed (27.65%,13/47).The 1-yearOS and DFS was 47.9% and 45.5% after transplantation.Conclusion TBI/FLAG-based regimen is safe and effective for refractory or relapsed leukemia,and the major risk still is relapse for refractory or relapsed leukemia patients after transplantation.The method of preventing recurrence needs to be further explored.
To explore the efficacy, and safety of the intensive conditioning regimen consisting of cladribine, cytarabine (Ara-C), and granulocyte colony-stimulating factor (G-CSF) plus modified busulfan (Bu) combined with cytoxan (Cy) (BuCy), prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with refractory, or relapsed acute myeloid leukemia (R/R AML).Thirty-Six R/R AML patients scheduled to receive allo-HSCT were consecutively, enrolled in this prospective study, and treated using intensive conditioning regimen consisting of CLAG plus modified BuCy. Median follow-up duration was 11.25 (range 0.5 - 21.0) months and the last follow up date was August 15, 2017.All patients (100%) achieved white blood cell (WBC) recovery within a median time of 16.00 (13.25 - 18.00) days, and 34 of them (94%) attained platelet (PLT) recovery within a median time of 13.50 (9.25 - 19.75) days. Incidence of acute graft-versus-host disease (aGVHD) was 50.00%, with median time of 71.50 (41.00 - 401.25) days. Three patients developed Grade I; nine, Grade II; 5, Grade III; and 1, Grade IV aGVHD. The incidence of chronic GVHD (cGVHD) was 44.40%, with median time of 255.00 (120.00 - 390.00) days. Four patients developed limited cGVHD, and 12, extensive cGVHD. One-year accumulating leukemia free survival (LFS), and overall survival (OS) rates between 52.98.8% to 69.4 +/- 7.7%, respectively. Eighteen (50%) patients were infected with cytomegalovirus; 2 (5.6%), with Epstein-Barr virus (EBV), 7 (19.4%), with hemorrhagic cystitis; 13 (36.1%), with bacteria; and 8 (22.2%), with fungus.Intensive conditioning regimen of CLAG plus modified BuCy for allo-HSCT may be effective and well-tolerated in R/R AML patients.
Objective To evaluate the safety and efficacy of haploidentical hematopoietic stem cell transplan-tation(haplo-HSCT)treatment in children with hematological diseases.Methods Fifty-nine cases of less than 14 years old children with hematonosis were analyzed retrospectively,who were enrolled in the Aerospace Central Hospital from July 2012 to June 2016.And the evaluation was carried out by analyzing the success rate of implantation,occu-rrence rate of graft versus host disease(GVHD),infection rate and transplant related mortality(TRM),cumulative re-currence rate,overall survival rate(OS)and disease-free survival rate(DFS).Results In total of 59 cases,the 59 engraftments were successfully transplanted,the median time of leukocyte engraftment was 18(8-23)days,the median time of platelet engraftment was 21(11-68)days,the bone marrow was assessed 28 days after transplanta-tion,which showed that 59 patients achieved complete remission(CR)and DNA test confirmed complete donor chime-rism.With a median of follow-up time of 19(5-56)months,the cumulative recurrence rates ofⅠ,Ⅱgrade andⅢ,Ⅳ grade acute GVHD were(38.3 ± 6.3)%(23 cases)and(16.7 ± 4.8)%(10 cases),respectively,the chronic GVHD cumulative recurrence rate was(65.6 ± 7.5)%(30 cases),the cytomegalovirus(CMV)viremia cumulative recurrence rate was(45.1 ± 6.5)%(27 cases),the Epstein-Barr virus(EBV)viremia cumulative recurrence rate was(10.0 ± 3.9)%(6 cases),the viral cystitis cumulative recurrence rate was(20.0 ± 5.5)%(12 cases),the transplant related mortality was(12.8 ± 6.0)%,the 2-year cumulative recurrence rate of CR group was(8.0 ± 5.4)%,and that of non-remission(NR)group was(64.1 ± 11.9)%.The 2-year OS of CR group was(78.9 ± 7.5)%,the 2-year OS of NR group was(32.5 ± 12.9)%,the 2-year DFS of CR group was(79.5 ± 9.8)%,the 2 years DFS of NR group was(27.4 ± 7.9)%.Conclusions Haplo-HSCT is safe and effective in treating children with hematonosis,and haplo-HSCT has high survival rate and low recurrent,especially when transplantation is per-formed in the remission stage.But the prognosis of haplo-HSCT is poor in the refractory and relapsed patients,and to explore the preventing recurrence measures are very urgent.
Whether a graft-versus-graft (GVG) response in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is associated with an enhanced graft-versus-leukemia (GVL) effect remains highly controversial. Furthermore, it is unknown if the GVG response overwhelms the impact of refractory acute leukemia. We aimed to compare the characteristics and therapeutic outcomes between patients undergoing a modified haploidentical cord blood (cord-haplo) HSCT protocol (n = 97) and those undergoing haploidentical HSCT (n = 42) for refractory acute leukemia. A reliable and stable predominant haploidentical donor chimerism was established. The 2-year relapse rate was more favorable in patients undergoing cord-haplo HSCT than in those undergoing haploidentical HSCT (25.9% versus 53.2%; P = .007), as was progression-free survival (PFS; 35.5% versus 17.9%; P = .049). Meanwhile, nonrelapse mortality at 2 years was not significantly different (38.0% versus 24.6%; P= .367). We also found that a higher number of mutual haploidentical donor-mismatched antigens, a concept similar to HLA mismatching, was associated with better disease control. Multivariate analysis identified cord-haplo HSCT as an independent significant predictor of reduced relapse (hazard ratio [HR], .44; P = .028) and improved PFS (HR, .58; P = .033), as was chronic graft-versus-host disease (GVHD) (relapse: HR, .42; P = .013; PFS: HR, .63: P = .052). However, the incidences of neutrophil and platelet engraftment, GVHD, and virus reactivation were comparable in the 2 groups. This study demonstrates that cord-haplo HSCT significantly enhances the GVL effect and improves PFS, providing a reliable and efficient therapeutic platform for patients with refractory acute leukemia. (C) 2018 American Society for Blood and Marrow Transplantation.