allo-HSCT In Complete Remission Research Articles

Allogeneic haematopoietic stem cell transplantation for adult T-lymphoblastic lymphoma: A real-world multicentre analysis inChina.

In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

HLA 1 Allele-Mismatched Unrelated Vs Haploidentical Donor Transplants in Acute Myeloid Leukemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative treatment for acute Myeloid Leukemia (AML) patients. When there is no HLA-identical sibling or unrelated donor, alternative donors such as 1 allele-mismatched unrelated donors (1-MMUD) or haploidentical donors (HID) may be considered. While there have been reports that the outcomes of these two donors are comparable with those of HLA-matched unrelated donors, there is limited data directly comparing the outcomes between 1-MMUD and HID transplantation. Therefore, we conducted an analysis of the outcomes of allo-HSCT from 1-MMUD and HID in AML patients. This study is a retrospective cohort study at a single institution, including patients with AML who underwent first allo-HSCT in complete remission (CR) or CR with incomplete hematologic recovery between 2002 and 2022, from 1-MMUD or HID. For HID transplantation, patients were administered fludarabine 30mg/BSA for 4 days, intravenous busulfan 3.2mg/kg for 2 days, and depending on the condition, they received either total body irradiation (TBI) at 400cGy or fractionated TBI at 800cGy (400cGy for 2 days). Graft-versus-host disease (GVHD) prophylaxis for HID transplantation consisted of antithymocyte globulin total 5.0mg/kg, methotrexate 5mg/BSA 3 or 4 times, and calcineurin inhibitors. In 1-MMUD transplantation, various myeloablative or reduced-intensity conditioning regimens were used. All patients received T-cell replete peripheral blood stem cells. A total of 108 patients who underwent 1-MMUD transplantation and 447 patients who underwent HID transplantation were included. The 1-MMUD group showed a tendency to be younger (median 42 years vs. 51 years, Wilcox rank-sum test p < 0.01) and had a lower proportion of ABO-matched transplantations (28.7% vs. 51.7%, Chi-square test p < 0.01). Other patient characteristics were similar between the two groups. In terms of survival, the median OS in the 1-MMUD group was 60.1 months, and in the HID group was 58.7 months, showing no significant difference between the two groups (Log rank test p = 0.81). Similarly, the median RFS was 54.8 months in the 1-MMUD group and 40.9 months in the HID group, with no statistically significant difference (Log rank test p = 0.96). The cumulative incidence of relapse and NRM at 60 months after allo-HSCT showed no significant difference between the two groups, with 26.1% and 25.7% for relapse and 23.9% and 26.3% for NRM in the 1-MMUD and HID groups, respectively (Gray's test p for relapse: 0.81, p for NRM: 0.82). Although the cumulative incidence of grade 2 or higher acute GVHD did not show a significant difference between the two groups (38.0% in 1-MMUD, 45.4% in HID, Gray's test p = 0.41), the incidence of chronic GVHD was significantly higher in the HID transplantation group (63.6%) compared to the 1-MMUD transplantation group (52.0%) (Gray's test p < 0.01). Finally, in a multivariate Cox model In conclusion, both 1-MMUD and HID can be considered equivalent alternative donors, and caution should be exercised regarding the occurrence of chronic GVHD in HID transplantation. Further comparisons between the two donors, including in different settings such as post-transplantation cyclophosphamide, warranted.

Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.

The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.

Donor-Derived CAR T Cells Engineered with Sleeping Beauty in Pediatric and Adult Patients with Acute Lymphoblastic Leukemia Relapsed Post-HSCT

IntroductionAllogeneic Chimeric Antigen Receptor (CAR) T cells engineered with non-viral methods offer a modality to reduce costs and logistical complexity of the viral process and allow lymphodepleted patients to access CAR T cell treatment. We recently proposed the use of Sleeping Beauty (SB) transposon to engineer donor-derived T cells differentiated according to the cytokine-induced killer (CIK) cell protocol (Magnani CF et al. J Clin Invest. 2021). We report here outcomes on B-cell acute lymphoblastic leukemia (B-ALL) patients, relapsing after transplantation, treated with donor-derived anti-CD19 CAR T cells (CARCIK-CD19).MethodsWe conducted an academic, multi-center, phase I/II dose-escalation trial in patients relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). The infusion product was manufactured in-house starting from 50 mL of peripheral blood from the HSCT donor by electroporation with GMP-grade plasmids. All patients underwent lymphodepletion with Fludarabine (30 mg/m 2/day x 4 days) and Cyclophosphamide (500 mg/m 2/day x 2 days), before proceeding to CARCIK-CD19 infusion. We used the Bayesian Optimal Interval (BOIN) design to define a four-dose escalation scheme. Primary objectives were to define the Maximum Tolerated Dose (MTD), safety, and feasibility. Secondary objectives included the assessment of complete hematologic response (CR), duration of response (DOR), progression-free (PFS), event-free (EFS), and overall survival (OS). This study was registered at ClinicalTrials.gov, NCT03389035.ResultsFrom January 2018 to June 2021, a total of 32 patients were screened, 26 enrolled (6 children and 20 adults) and 21 infused (4 children and 17 adults). Reasons for not receiving infusion included consent withdrawal (N=1), disease progression not controlled by bridging therapy (N=3), acquisition of myeloid phenotype (N=1). The median number of prior therapies was 4 (range, 1-7) with a median time interval from HSCT to relapse of 9 months. The median BM blasts was 60% (range, 5-100%) at enrollment and 7% (range, 0-96%) post lymphodepletion. Of the 21 patients infused, CARCIK-CD19 were obtained by HLA-identical sibling (n=6, 29%), matched unrelated (n= 7, 33%), and haploidentical donors (n=8, 38%). Three patients (14%) received the first dose level of 1x10 6 CARCIK-CD19 cells/Kg, three (14%) the second of 3x10 6, and three (14%) the third of 7.5x10 6 whereas 12 patients (57%) received the fourth and last planned dose level of 15x10 6 cells/Kg, as no dose limiting toxicity (DLT) was observed. CRS was observed in six patients (three grade I and three grade II) and immune effector cell-associated neurotoxicity in two patients at the highest dose. Although 9 out of 21 had experienced acute or chronic graft-versus-host disease (GvHD) after the previous HSCT, secondary GvHD was never induced by CARCIK-CD19. Complete response was achieved by 13 out of 21 patients (61.9%, 95%CI=38-82%) and by 11 out of 15 patients treated with the 2 highest doses (73.3%, 95%CI=45-92%). Eleven of these responders were MRD-negative. Notably, the type of donor did not influence the achievement of CR 28 days post-infusion. At a median follow up of 21.6 months (range, 1.0-38.4 months), 10 patients (47.6%) are alive in CR (9 in the 2 highest dose levels). Overall, the median OS and EFS were 9.7 and 3.2 months, respectively, with a median DOR of 4.0 months (range, 1.0-23.5 months). Patients in CR at 28-days had a 6-months relapse-free survival of 48.4% (SE=14.9). EFS at 6 months was 26.5% (SE=9.9) and OS was 67.6% (SE=11.1). Among the 13 patients who achieved CR, two children underwent consolidation with a second allo-HSCT in complete remission. Adult patients did not receive any additional anti-leukemic therapies unless a relapse occurred, and four of them remained in remission and alive (+24, +9, +6, and +4 months). Robust CARCIK-CD19 cell expansion was achieved in most patients and CARCIK-CD19 cells were measurable for up to 22 months.ConclusionsSB-engineered CAR T cells induce sustained responses in B-ALL patients relapsed after HSCT irrespective of the donor type and without severe toxicities. DisclosuresLussana: Incyte: Honoraria; Pfizer: Honoraria; Astellas Pharma: Honoraria; Amgen: Honoraria. Gritti: Takeda: Consultancy; Roche: Consultancy; Kite Gilead: Consultancy; IQvia: Consultancy; Italfarmaco: Consultancy; Clinigen: Consultancy. Biondi: Incyte: Consultancy, Other: Advisory Board; Bluebird: Other: Advisory Board; Novartis: Honoraria; Amgen: Honoraria; Colmmune: Honoraria.

Viral Reactivation in Acute Leukemia Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation in Complete Remission: Stimulation of the Immune System

Background: Many studies have evaluated the impact of cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) showing a significant association with reduced risk of relapse while other studies failed to show the same results. On the other hand, other frequent viral infections or reactivations like Epstein-Barr virus (EBV), Human Herpesvirus 6 (HHV6) and BK virus (BK-V) have not been evaluated in the same context and/or together with CMV. The aim of this study is to evaluate the impact of CMV, EBV, HHV6 and BK-V reactivation in acute leukemia (AL) patients receiving allo-HSCT in complete remission (CR) and evaluate their impact alone or associated on disease relapse. Patients and methods: We evaluated 158 consecutive AL patients who received allo-HSCT at our center between January 2008 and June 2015; 95 (60%) were males, median age was 46 years (range: 18-67), 101 (64%) had acute myeloid leukemia (AML) and 57 (36%) had acute lymphoblastic leukemia (ALL). At transplantation, 114 (72%) patients were in first complete response (CR1) and 44 (28%) were in second CR (CR2). Conditioning regimen was myeloablative for 97 (61%) patients and of reduced intensity in 61 (39%) patients. DNA levels of CMV, EBV, HHV6 and BK-V were detected by quantitative RQ-PCR after weekly monitoring up to 3 months after allo-HSCT. CMV-DNA, EBV-DNA, HHV6-DNA or BK-V-DNA was considered positive when the copies exceeded 1000 copies/ml. Results: Among 158 patients, 45 (28%) patients had CMV reactivation after a median time of 40 days (6-72) after allo-HSCT; 53 (34%) patients had EBV reactivation after a median time of 42 days (18-91) after allo-HSCT; 33 (21%) patients had HHV6 reactivation after a median time of 24 days (6-69) and 30 (19%) patients had BK-V reactivation after a median time of 32 days (6-60) after allo-HSCT. There was 61 (39%) patients who did not have any viral reactivation, 46 (29%) patients who had only one reactivation (no matter the type), and 51 (32%) patients who had at least two or more co-reactivations (group 1). When evaluating relapse incidence, we found that patients who had only one reactivation were not significantly different from those who did not have any reactivation, with a comparable relapse incidence, thus, we analyzed those patients as one group (group 2, n=107). The cumulative incidence of relapse at 6 months for group 1 and group 2 was 2% (95% CI: 0.2-9.4) and 15.9 % (95%CI: 9.7-23.5) respectively, this result remained significantly different when stratifying on the type of conditioning, in RIC: 15.8% (95%CI: 3.7-35.7) vs 21.4% (95%CI: 10.5-35) respectively; and in MAC: 0 % vs 15.4% (95%CI: 7.8-25.3) respectively, p=0.04. This finding was confirmed independently of the presence of GVHD or not. Conclusion: We demonstrate here for the first time, in this homogeneous population, that co-reactivation of multiple viruses after allo-HSCT could lead to a lower incidence of relapse in AL patients in CR; this can be explained as a stimulation of the immune system via both the functional activation and amplification of NK compartment. This could also explain some conflicting results in studies evaluating single viral reactivation alone without consideration of other reactivations. These encouraging results should be validated at a larger multicenter level. Disclosures No relevant conflicts of interest to declare.

Prognostic analysis of allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in complete remission in the era of tyrosine kinase inhibitors

目的探讨在酪氨酸激酶抑制剂（TKI）时代Ph染色体阳性急性淋巴细胞白血病（Ph+ALL）在完全缓解（CR）状态下行异基因造血干细胞移植（allo-HSCT）的预后和影响因素。方法回顾性分析2012年5月至2017年5月河北燕达陆道培医院收治的116例在CR状态下行allo-HSCT的Ph+ALL患者的预后及其影响因素。结果116例患者中男72例，女44例。中位年龄20（4～64）岁。同胞全相合移植21例，亲缘单倍型移植77例，非血缘移植18例。5年总生存（OS）率为73.2％（95％CI 63.8％～80.5％），其中诊断至移植间隔时间<180 d的亚组5年OS率为87.5％。5年无病生存（DFS）率为61.4％（95％CI 51.8％～69.7％）。5年细胞形态及分子学水平复发累积发生率为18.5％（95％CI 12.6％～27.3％）。5年移植相关死亡率（TRM）为19.9％（95％CI 13.8％～28.7％）。多因素分析显示，15～39岁（HR＝2.730，P＝0.044）、诊断至移植间隔时间≥180 d（HR＝4.534，P＝0.010）、发生Ⅲ～Ⅳ度急性移植物抗宿主病（aGVHD）（HR＝7.558，P＝0.000）是影响患者OS的不利因素；发生局限型慢性移植物抗宿主病（cGVHD）是影响患者OS的有利因素（HR＝0.300，P＝0.034）。而性别、起病时WBC（<30×109/L，≥30×109/L）、BCR-ABL融合基因类型、体细胞突变类型、移植前状态（CR1，>CR1）、移植前微小残留病（MRD）水平（MRD阴性，MRD阳性）、预处理方案（全身照射方案，白消安为基础方案）、预处理方案强度、移植类型、GVHD预防方案（环孢素A，他克莫司）、抗胸腺细胞免疫球蛋白的种类、巨细胞病毒和EB病毒血症的有无对OS的影响无统计学意义。结论TKI时代Ph+ALL在CR状态下行allo-HSCT时，影响生存的因素有年龄、诊断至移植间隔时间和发生重度aGVHD。

The burden of hepatitis E among patients with haematological malignancies: A retrospective European cohort study

The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity. The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution. Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective.

Clinical features and prognosis in CD10(-) pre-B acute lymphoblastic leukemia

目的分析CD10阴性的前B急性淋巴细胞白血病（CD10−pre B-ALL）患者的临床特征和预后。方法对6例成人CD10− pre B-ALL患者的临床和实验室资料进行回顾性分析，结合文献复习明确该类型患者的临床特征及预后。结果CD10−pre B-ALL占ALL的1.5%（6/409），占B-ALL的1.8%（6/343），占pre B-ALL的11.5%（6/52）。6例患者均为男性，中位年龄为33.5岁，起病时中位WBC为101.78×109/L，所有患者均伴有MLL-AF4融合基因表达。5例患者经1个疗程诱导化疗即获得完全缓解（CR），1例患者经3个疗程化疗后才获得CR。2例患者在CR1期行异基因造血干细胞移植（allo-HSCT），1例患者CR后短期内即复发，在CR2期行allo-HSCT。1例患者正在等待移植。2例未移植患者1例复发死亡，1例尚处于缓解状态。结论CD10−pre B-ALL是一类具有独特临床特征的成人ALL亚型，发生率较低，常见于男性，起病时白细胞水平较高，MLL-AF4融合基因表达率高，常规化疗具有较高的缓解率，但易复发，allo-HSCT有可能改善其预后。

Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia

目的评价高三尖杉酯碱、阿糖胞苷、柔红霉素或去甲氧柔红霉素(HAD/HAI)方案诱导治疗初治急性髓系白血病(AML)患者的长期疗效并探讨其影响因素。方法观察HAD/HAI方案治疗1个疗程后初治143例AML患者的完全缓解(CR)、总生存(OS)及无复发生存(RFS)率，分析WHO 2008标准诊断分型、遗传学预后分组及初始WBC等因素对患者OS、RFS率的影响，评估中剂量阿糖胞苷(MD-Ara-C)巩固治疗在提高AML患者长期生存中的作用。结果143例患者中112例(78.3%)1个疗程获CR。仅1例患者在诱导化疗期早期死亡。高白细胞与非高白细胞组、FLT3-ITD突变型与野生型组患者CR率差异均无统计学意义(P值分别为0.266和0.528)。遗传学预后良好、中等、不良组患者CR率分别为93.7%、71.4％和61.3%，组间差异有统计学意义(P=0.001)。中位随访24(1~104)个月，中位生存时间为30(95%CI 12~48)个月。所有患者的5年OS率为40.0%，5年RFS率为37.0%。1个疗程CR后接受巩固治疗的患者为96例，5年OS率为47.0%，5年RFS率为38.0%；其中序贯含MD-Ara-C方案(71例)和序贯标准剂量Ara-C(25例)巩固治疗组患者的5年OS率差异有统计学意义(58.0％对19.0%，P=0.004)。在序贯含MD-Ara-C方案巩固治疗的患者中，高白细胞与非高白细胞组、FLT3-ITD突变型和野生型组患者的5年OS率差异均无统计学意义(P值分别为0.419和0.482)，遗传学预后良好、中等、不良组患者5年OS率差异无统计学意义(P=0.332)。结论HAD/HAI方案诱导化疗缓解后序贯含MD-Ara-C方案巩固治疗的策略对初治AML患者，特别是高白细胞患者，可望获得满意的长期生存率。

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.

Clinical and laboratory characteristics of 12 Ph/BCR-ABL positive acute myeloid leukemia patients

目的探讨有利于Ph染色体和（或）BCR-ABL融合基因阳性急性髓系白血病（Ph/BCRABL+ AML）诊断的临床和实验室特征。方法收集2006年2月至2013年12月收治的12例Ph/BCR-ABL+ AML患者资料，以典型慢性髓性白血病急髓变（CML-MBC）患者为对照组，回顾性分析两者临床及实验室特征，并随访生存情况。结果12例患者中位年龄27.5岁，无或轻度脾脏肿大者10例（83.3%），FAB分型以M2和M4为主，中位外周血和骨髓嗜碱粒细胞比例、巨核细胞数低于典型CML-MBC患者。免疫表型均为髓系表达，表达CD34者8例（66.7%）。11例患者检测到t(9;22)，伴附加染色体异常5例（45.5%），其中1例为inv(16）。12例患者均检测到BCR-ABL融合基因，e1a2型3例（25.0%），余为b2a2/b3a2型，其中1例伴有CBFβ-MYH11表达。6例受检患者中2例存在AML常见突变，其中CEBPA突变1例，FLT3-TKD突变1例。诱导治疗完全缓解(CR) 7例（58.3%），7例接受化疗联合酪氨酸激酶抑制剂（TKI）者6例CR，3例接受单独化疗者1例CR。总体中位生存期16.5个月，异基因造血干细胞移植（allo-HSCT）组为33.5个月，高于非移植组（5.5个月）。结论e1a2型融合基因、与AML常见融合基因共表达、存在AML常见突变有利于Ph/BCR-ABL+ AML诊断；此类患者诱导缓解率低，生存期短，化疗联合TKI获得缓解后尽早行allo-HSCT是改善其生存的唯一有效途径。

Comparison of Allogeneic Hematopoietic Stem Cell Transplant from HLA-Matched Related Donors and from Unrelated Donors for Intermediate- to High-Risk Adult Acute Myeloid Leukemia in Remission

Introduction: Allogeneic hematopoietic stem cell transplant (allo-HSCT) is currently the most powerful method to treat intermediate- to high-risk acute myeloid leukemia (AML). Human leukocyte antigen (HLA) matched related donors (MRD) are considered the best donors in allo-HSCT, but they are only available for a small proportion of patients. With the progress of transplant skills over decades, outcome of unrelated donor (URD) HSCT has improved significantly, and the difference between MRD and URD HSCT has been steadily declining. But the role of URD HSCT has still not been well defined in AML, especially for different risk groups. We therefore compared the results of URD HSCT with MRD HSCT in adult AML patients with intermediate- to high-risk in our center.Methods: During January 2005 to December 2012, 108 adult patients with intermediate- or high-risk AML receiving allo-HSCT in complete remission (CR) in our center were admitted in this study. All patients received a standard-dose cytarabine with anthracycline or homoharringtonine as induction therapy. Consolidation courses include high-dose cytarabine or standard-dose cytarabine with anthracycline, homoharringtonine, or mitoxantrone. After consolidation, all patients received allo-HSCT in CR. High resolution DNA typing for HLA-A, -B, -C, -DRB1, and -DQB1 was performed during CR. Patients with HRD would receive HRD HSCT; while for those without HRD, URD with at least 8/10 locus match were selected as donor source. Among the 108 patients, 51 received grafts from HRD and 62 from URD. The conditioning regimen mainly involved BuCy without total body irradiation. All patients received graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine A, methotrexate and low-dose mycophenolate mofetil. Rabbit antithymocyte globulin (Thymoglobulin, IMTIX-SangStat, Lyon, France) was also administered to some patients receiving URD HSCT (4.5–6 mg/kg total dose).Results: Most of the baseline characteristics were well balanced between two groups. However, The interval from diagnosis to transplantation differed significantly between two groups, with a median interval of 7 months for HRD group versus 10 months for URD group (P=0.008). Bone marrow was used as graft source in 100% and 80.7% of patients in HRD and URD groups, respectively. Another 19.3% of patients in URD group received peripheral blood stem cell as graft source. The median follow-up was 37.5 months in the whole cohort.The cumulative incidence of acute grade 2 to 4 GVHD was significantly higher in URD group compared with HRD group (40.3% vs. 13.8%, P=0.002). Chronic GVHD and extensive chronic GVHD were also significantly more frequent in URD group (chronic GVHD: 49.2% vs. 29.6%, P=0.037; extensive chronic GVHD: 22.0% vs. 3.7%, P=0.005). The treatment-related mortality (TRM) was significantly higher in the URD group (17.9% vs. 4.3%, P=0.015). While the overall survival (OS), relapse-free survival (RFS), and relapse rate were comparable between two groups (OS at 3 years: HRD 79.9% vs. URD 70.3%, P=0.146; RFS at 3 years: HRD 73.1% vs. URD 66.7%, P=0.239; relapse rate at 3 years: HRD 23.5% vs. URD 18.0%, P=0.643). Clinical characteristics were subjected into univariate and multivariate Cox analysis for OS to find prognostic factors. Cytogenetics, status at transplant (CR1 vs. CR2 to CR3), and MRD levels at transplant were identified as factors that were significantly associated with OS, whereas donor type had no significant impact.When the analysis was done in patients divided by risk stratification, we found that for intermediate-risk patients, the HRD group had a 3-year improved survival rate than URD group (RFS: 85.2% vs. 70.5%, P=0.043; OS: 85.2% vs. 72.7%, P=0.062) with a significantly reduced TRM rate (3.8% vs. 18%, P=0.025). The relapse rate were comparable between two groups (HRD 11.3% vs. URD 12.7%, P=0.649). While for high-risk patients, no differences were observed between two groups in terms of OS, RFS, TRM and relapse rate.Conclusions: For intermediate-risk AML patients, compared with URD HSCT, the results from HRD HSCT were better with improved survival rate and reduced TRM; while for high-risk AML patients, donor types had no effect on transplant outcome. Cytogenetics, status at transplant, and MRD levels at transplant were found to be independent prognostic factors for OS. DisclosuresNo relevant conflicts of interest to declare.

In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification

AbstractWe asked whether minimal residual disease (MRD) determined by RUNX1/RUNX1T1 transcript levels could identify allogeneic hematopoietic stem cell transplantation (allo-HSCT) t(8;21) (q22;q22) acute myeloid leukemia patients who are at high risk for relapse, together with the impact of c-KIT mutations. Ninety-two consecutive adult t(8;21) patients who received allo-HSCT in complete remission were enrolled. MRD status at 1, 2, and 3 months after HSCT identified relapse patients (P = .05, P < .001, P = .0001, respectively). The 2-year cumulative incidence of relapse (CIR) and leukemia-free survival (LFS) was 32% vs 9% (P = .01) and 55% vs 70% (P = .12) for patients with and without c-KIT mutations, respectively. In multivariate analysis, MRD at the first 3 months after HSCT, rather than c-KIT mutations, was an independent factor for CIR (P = .001) and LFS (P = .001). In addition, 17 patients received donor lymphocyte infusion (DLI) as interventional therapy for MRD, and the 2-year CIR and LFS for patients with or without DLI was 24% vs 87% (P = .001) and 64% vs 0% (P < .001), respectively. In conclusion, MRD monitoring early after transplant allows further rapid identification of t(8;21) patients at high risk of relapse and was more predictive of relapse risk than c-KIT mutations.