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Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes. The complete remission (CR) rate and minimal residual disease (MRD)-negative CR rate of CAG-like regimens were significantly higher compared with conventional ALL regimens (CAG-like: 80.0% and 59.7%, respectively; P = .039; ALL: 51.4% and 31.3%, respectively; P = .048). Overall, 90.0% of cases (18/20) achieved CR using combined decitabine and CAG-like regimens. Additionally, CAG-like regimens had lower rates of grade 3 or 4 infection (18.8% vs. 38.2%; P = .059) and grade 1 or 2 hepatotoxicity (37.5% vs. 60.0%; P = .043) than conventional ALL regimens. The 38 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first CR (CR1) had better overall survival (OS) and leukemia-free survival (LFS) than the 11 patients who underwent allo-HSCT in the second CR (CR2) or in no remission (median OS not reached vs. 7.6 months, P = .0004; median LFS not reached vs. 11.6 months, P = .0008). There was a significant difference in 3-year OS (95.7% vs. 52.5%; P = .0039) and LFS (95.8% vs. 43.5%; P = .0003) after allo-HSCT between pre-transplant MRD-negative and MRD-positive patients. The median OS for patients without allo-HSCT was 32.1 months in the CAG-like group compared with 12.1 months in the non-CAG-like group (P = .019). These findings suggest that ETP-ALL and T/M-MPAL possess overlapping characteristics and CAG-like regimens improve their clinical outcomes.

•Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be an optimal first-line consolidation therapy for core binding factor (CBF) acute myelogenous leukemia (AML) with intermediate- and adverse-risk genetics.•Minimal residual disease (MRD) at the second and third months after allo-HSCT could predict relapse in t(8;21) AML patients.•Haploidentical HSCT could improve the survival of MRD-positive CBF-AML patients with intermediate- and adverse-risk genetics.

ABSTRACTSpinster homolog 3 (SPNS3) belongs to the Spinster (SPNS) family which participates in sphingolipid transportation through the cell membrane. However, the functions of SPNS3 in acute myeloid leukemia (AML) are unknown. This study obtained SPNS3 from a gene set that was related to AML relapse and evaluate whether high SPNS3 expression induced apoptosis resistance in an AML cell line, which is consistent with the role of SPNS3 as a marker of poor prognosis in the clinic. Moreover, internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation and the AC127521.1/ MIR-139/SPNS3 competing endogenous RNA axis were found to regulate SPNS3 expression. In addition, we noted that SPNS3 may play an important role in the Sphingosine-1-phosphate signal pathway that is involved in the maintenance of the AML microenvironment. These results highlight the anti-apoptosis effect of SPNS3 in AML, and the potential mechanism mediating this effect was explored through bioinformatics.Abbreviations:AML: acute myeloid leukemia; FLT3-ITD: internal tandem duplication of FMS-like tyrosine kinase 3; SPNS3: spinster homolog 3; SPNS1: spinster homolog 1; SPNS2: spinster homolog 2; GO: gene ontology; S1P: sphingosine-1-phosphate; ceRNA: competing endogenous RNA; dAML: acute myeloid leukemia at diagnosis; iAML: acute myeloid leukemia after induction chemotherapy; rAML: acute myeloid leukemia at relapse; DEGs: differentially expressed genes; BP: biological processes; CC: cellular components; MF: molecular functions; MRD: minimal residual disease; EFS: event-free survival; OS: overall survival; KEGG: Kyoto Encyclopedia of Genes and Genomes; SPHK: Sphingosine kinase.

We analyzed the outcomes of 146 severe aplastic anemia (SAA) patients who received a combination of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) and an unrelated cord-blood (UCB) unit between September 2011 and December 2017. One hundred and seventeen patients underwent transplantation as first-line therapy. Seven patients experienced early mortality, and among the evaluable 139 patients, one patient experienced primary graft failure (GF), while the other 138 patients achieved successful haploidentical donor engraftment; additionally, three patients experienced secondary GF. Six patients demonstrated delayed platelet recovery, and three patients demonstrated platelet GF. The median time for myeloid and platelet engraftment was 11 (range: 9–28) days and 15 (range: 9–330) days, respectively. With a median follow-up of 40 (range: 18–93) months, the cumulative incidences were 31.43% and 10.00% for grades II–IV and grades III–IV acute graft-versus-host disease (GVHD), respectively. The cumulative incidences of chronic GVHD (cGVHD) and moderate–severe cGVHD were 36.23% and 11.71%, respectively. There was no patient relapse. The probabilities of 4-year overall survival and GVHD-free, failure-free survival were 81.4 ± 3.3% and 69.2 ± 3.9%, respectively. These encouraging preliminary results indicated that haplo-HSCT combined with the infusion of UCB is a feasible choice for SAA patients without matched donors.

Epstein–Barr virus (EBV) reactivation after allogeneic hematopoietic cell transplantation (allo-HCT) is one of the major concerns that may lead to fatal EBV diseases. However, updated data are needed because of the remarkable evolution of the HCT protocol and donor selection. We conducted a retrospective study that enrolled 890 allo-HCT recipients. Independent risk factors for EBV reactivation were use of antithymocyte globulin, haploidentical donor, and the presence of chronic graft-versus-host disease. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively (P< 0.001). Posttransplant lymphoproliferative disorders (PTLDs) occurred in seven patients. EBV reactivation was associated with inferior survival in recipients who survived more than 2 years post-HCT (P< 0.001) but might time-dependently benefit those patients with malignancies by decreasing relapse incidence (P= 0.046). A decreased relapse incidence was observed 1 year after HCT for recipients at first or second remission (P= 0.042) and in the first year post-HCT for recipients with advanced diseases (P= 0.032). We concluded that with current management, PTLDs were efficiently controlled, but EBV reactivation still had a multifactorial impact on transplant outcomes. Multicenter prospective studies are warranted to validate these findings.

Background：

Backgrounds:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL). Relapse post-HSCT remains the major cause of mortality, highlighting the urgent need for more effective conditioning regimens in reducing relapse rates and improving outcomes for T-cell malignancy. Chidamide, as the first oral subtype-selective histone deacetylase inhibitor (HDACi) approved in China, can lead to a more relaxed chromatin structure through chromatin remodeling, particularly hyperacetylation of lysine residues in the histone tails, which facilitates the expression of tumor suppressor genes as well as the action of alkylating agents busulfan. To date, the role of chidamide in T-ALL/LBL conditioning regimens in allo-HSCT has not been explored.

Introduction:Thrombocytopenia is a common complication after hematopoietic stem cell transplantation (HSCT) and is strongly associated with transplant-related morbidity and mortality. According to the statistics, the incidence of post-HSCT thrombocytopenia is about 5%-37%. So far, there is no standard treatment regimen for thrombocytopenia after HSCT.

Background：

Background:Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous type of acute leukemia that displays an ambiguous pattern of antigen expression to a degree that assigning a single lineage of origin is not possible due to which, understanding of the pathophysiology of the disease, diagnosis and treatment are limited. The lack of well-established optimal treatment for MPAL has paved path for requirement of a more effective and less toxic approach. Blinatumomab, a bispecific CD19-directed CD3 T-cell engager (BiTE) antibody and venetoclax, a potent, highly selective B-cell leukemia/lymphoma-2 (BCL2) inhibitor was approved for the treatment relapsed/refractory (r/r) B-acute lymphoblastic leukemia (B-ALL) and chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), respectively. Here, we present 6 patients with CD19-positive MPAL that are successfully treated with blinatumomab in combination with venetoclax and/or azacytidine in front line setting.

We retrospectively analyzed the outcomes of 214 patients with severe aplastic anemia (SAA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with rabbit anti-thymocyte globulin (r-ATG) or ATG-Fresenius (ATG-F). Using propensity score matching, we performed a case-control study comparing 44 and 23 patients in the r-ATG and ATG-F groups, respectively. The median time was 11 versus 11 days (P = .368) for myeloid engraftment and 11 versus 13 days (P = .030) for platelet engraftment in the r-ATG and ATG-F groups, respectively. The r-ATG group showed a lower incidence of grade III to IV acute graft-versus-host disease (GVHD) than the ATG-F group (2.27% versus 17.39%, P = .026). Similar outcomes were observed between the r-ATG and ATG-F groups for infection rate (59.09% versus 56.52%, P = .840), grade II to IV acute GVHD (20.45% versus 21.74%, P = .948), overall incidence of chronic GVHD (26.83% versus 22.73%, P = .704), moderate to severe chronic GVHD (9.76% versus 13.64%, P = .648), and transplantation-related mortality (11.36% versus 4.35%, P = .614). There was no statistical difference in 5-year overall survival (86.40% versus 95.7%, P = .245); GVHD-free, failure-free survival (77.30% versus 78.30%, P = .986); or health-related quality of life (P> .05) between r-ATG and ATG-F.

Background:CD19 chimeric antigen receptor T (CAR-T) cells therapy has shown great success in B-cell acute lymphoblastic leukemia (B-ALL). To reduce the possibility of relapse due to CD19 antigen loss, sequential CD19/CD22 and tandem CD19/CD22 dual targets CAR-T cells have been developed. However, the optimal combination strategy of target antigens for CAR-T cells is still uncertain. This study was designed to compare the efficacy and safety of single CD19, tandem CD19/CD22 and sequential CD19/CD22 CAR-T cells therapies in relapsed/refractory(R/R) B-ALL patients.

Background:

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We retrospectively analyzed the outcomes of 214 patients with severe aplastic anemia (SAA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with rabbit anti-thymocyte globulin (r-ATG) or ATG-Fresenius (ATG-F). Using propensity score matching, we performed a case-control study comparing 44 and 23 patients in the r-ATG and ATG-F groups, respectively. The median time was 11 versus 11 days (P = .368) for myeloid engraftment and 11 versus 13 days (P = .030) for platelet engraftment in the r-ATG and ATG-F groups, respectively. The r-ATG group showed a lower incidence of grade III to IV acute graft-versus-host disease (GVHD) than the ATG-F group (2.27% versus 17.39%, P = .026). Similar outcomes were observed between the r-ATG and ATG-F groups for infection rate (59.09% versus 56.52%, P = .840), grade II to IV acute GVHD (20.45% versus 21.74%, P = .948), overall incidence of chronic GVHD (26.83% versus 22.73%, P = .704), moderate to severe chronic GVHD (9.76% versus 13.64%, P = .648), and transplantation-related mortality (11.36% versus 4.35%, P = .614). There was no statistical difference in 5-year overall survival (86.40% versus 95.7%, P = .245); GVHD-free, failure-free survival (77.30% versus 78.30%, P = .986); or health-related quality of life (P> .05) between r-ATG and ATG-F.

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Background:Relapse remains the main cause of treatment failure post transplantation. Relapse prevention is an important strategy for acute myeloid leukemia (AML) patients.

Background:Haematopoietic stem cell transplantation (HSCT) is the only curative therapy for paroxysmal nocturnal haemoglobinuria (PNH). Haploidentical HSCT (haplo-HSCT) is an alternative treatment method for PNH patients lacking suitable identical donors. The current study evaluated the feasibility of haplo-HSCT in PNH patients.

Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). Studies have evaluated the feasibility of upfront haploidentical HSCT in SAA patients. We previously conducted a single-arm prospective study in 50 patients who received the combination of HID-HSCT and an unrelated umbilical cord blood unit for the treatment of hematological malignancies. To the best of our knowledge, there is no combination of HID-HSCT and an unrelated umbilical cord blood unit for SAA. Now, we report the outcomes of combination of HID-HSCT with an unrelated cord blood unit for 127 patients with SAA in our center from September 2011 to April 2017. The clinical data of 127 SAA patients, including 74 male patients and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age was 23.5 years (range 3.0-54.0). 39 patients of failure to IST as salvage therapy, 88 patients underwent upfront transplantation. The median interval from SAA diagnosis to SCT was 2.0 months (range 0.5-180.0). Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates, and HLA matching was prioritized over cell dose. At the same level of typing, the richest UCB units were chosen. The conditioning regimen was modified BU/CY-based regimen. Prophylaxis for graft-versus host disease (GVHD): cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×108/kg in the haploidentical grafts and 2.22 (1.10-7.30)×107/kg in the cord blood units. The median doses of CD34+cells infused were 3.49(1.02-8.89)×106/kg and 0.56 (0.16-2.27)×105/kg, respectively. One patient occurred primary graft failure. All surviving patients attained complete haploidentical engraftment. The median time for myeloid engraftment was 11 (range, 9-28) days and 15 (range, 9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. With a median follow-up of 20.5(4.0-60.0) months, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 24.8%, moderate-severe chronic GVHD was 14.4%, 4-year estimated overall survival (OS) was 78.5% ± 4.3%. In conclusion, combination of HID-HSCT and an unrelated umbilical cord blood unit is a feasible choice for SAA with favourable outcomes.

ObjectiveTo evaluate the outcomes of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA).

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Objective:To evaluate the impact of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of patients with refractory and relapsed acute lymphoblastic leukemia(ALL).

Purpose:The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) therapy for refractory or relapsed (R/R) aggressive non-Hodgkin lymphoma (NHL) patients was still unknown. In this study, we aimed to explore the clinical outcome of R/R aggressive NHL patients received haplo-HSCT treatment.

Objective:To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL).

The aim of this study was to evaluate the diagnostic and prognostic value of miR-155 in Chinese acute myeloid leukemia (AML) patients. The miR-155 levels of 142 de novo AML patients and 28 healthy donors were detected by real-time quantitative PCR (RQ-PCR). The miR-155 expression was significantly up-regulated in AML compared with control (p<0.001). A receiver operating characteristic (ROC) curve revealed that miR-155 expression could differentiate patients with AML from control subjects (AUC=0.907, 95%CI: 0.853-0.960, P<0.001). We also monitored the miR-155 level in 22 de novo AML patients and found that the miR-155 level decreased significantly from the initial diagnosis to post-CR (P<0.001). FLT3 internal tandem duplication (FLT3-ITD) mutation was significantly more frequent in miR-155 high-expressed group versus low-expressed group (p=0.002). Considering all patients, miR-155 high-expressed cases had significantly lower complete remission (CR) and part remission (PR) rate than miR-155 low-expressed cases (p=0.04). Survival analysis was performed in non-M3-AML patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) as consolidation therapy. Kaplan-Meier demonstrated that there was no difference in leukemia free survival (LFS) and overall survival (OS) between miR-155 high-expressed and low-expressed patients (p>0.05). Collectively, Increased miR-155 expression is associated with FLT3-ITD mutation and poor therapy response in Chinese AML and allo-HSCT could improve survival of these patients.

Objective:To determine the efficacy and safety of IFN-α-2b pre-emptive therapy for acute leukemia(AL) patients with relapsing tendencies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Background:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment options to hematologic malignancies. However, majority of patients with refractory or resistant AML/MDS can not achieve remission before transplantation. It is necessary to design a safe and effective conditioning regimen to reduce tumour burden, improve remission rates, decrease transplantation-related mortality, and improve disease-free survival (DFS) in patients with advanced acute myloid leukemia(AML) and myelodysplastic syndrom(MDS). One of the promising drugs of epigenetics is decitabine (DAC), which has a significant effect on a variety of hematologic malignancies including MDS and advanced AML. Furthermore, decitabine can not only up-modulate the tumor-associated antigen express on surface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also can reduce the incidence of graft-versus-host disease (GVHD) by increase the number of regulatory T Cells (Tregs).

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Objective