Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

Ponatinib therapy in recurrent Philadelphia chromosome-positive central nervous system leukemia with T315I mutation after Allo-HSCT.

Central nervous system leukemia (CNSL) relapse is relatively common among Philadelphia chromosome-positive (Ph+) leukemia patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The prognosis of patients is dismal for those with a BCR-ABL T315I mutation, which is resistant to TKIs including second-generation drugs. We assessed ponatinib for nine patients with recurrent Ph+ CNSL and a T315I mutation after allo-HSCT, including five patients with Ph+ acute lymphoblastic leukemia and four with chronic myelogenous leukemia. Five patients experienced isolated CNSL relapse, and four experienced CNSL with hematologic relapse. All patients received ponatinib combined with intrathecal chemotherapy, and four patients with hematologic relapse received systemic chemotherapy and/or donor lymphocyte infusion. All patients achieved a deep molecular response and central nervous system remission (CNSR) at a median time of 1.5 (range: 0.7-3) months after ponatinib treatment. Two patients experienced a second CNSL relapse due to ponatinib reduction, but they achieved CNSR again after an increase to the standard dosage. Six patients developed graft versus host disease. By April 1, 2019, eight patients were alive, and one died of pneumonia. The median time of survival after the first CNSL relapse posttransplantation was 18 (range: 11.2-48.5) months. Our data from a small number of samples suggests that ponatinib is effective for recurrent Ph+ CNSL patients with a BCR-ABL T315I mutation after allo-HSCT and warrants broader clinical evaluation.

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard-risk acute lymphoblastic leukaemia in first complete remission.

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard-risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III-IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5-year cumulative transplant-related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5-year relapse rate post-transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5-year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5-year disease-free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3-year GVHD-free, relapse-free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard-risk adults with ALL in CR1 who lack matched donors.

Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study.

The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are well established. Previous single-center studies have demonstrated similar survival after unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic malignancies. To test the hypothesis that haploidentical HSCT would be a valid option as postremission therapy for AML patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multicenter study. Between July 2010 and November 2013, 450 patients were assigned to undergo HID (231 patients) or ISD HSCT (219 patients) according to donor availability. Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34), respectively; the overall survival rate was 79% and 82% (P = .36), respectively; cumulative incidences of relapse were 15% and 15% (P = .98); and those of the nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediate- or high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940.

Mesenchymal stem cells versus mesenchymal stem cells combined with cord blood for engraftment failure after autologous hematopoietic stem cell transplantation: a pilot prospective, open-label, randomized trial.

Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.

A FTA-based method for risk decision-making in emergency response.

Decision-making problems in emergency response are usually risky and uncertain due to the limited decision data and possible evolvement of emergency scenarios. This paper focuses on a risk decision-making problem in emergency response with several distinct characteristics including dynamic evolvement process of emergency, multiple scenarios, and impact of response actions on the emergency scenarios. A method based on Fault Tree Analysis (FTA) is proposed to solve the problem. By analyzing the evolvement process of emergency, the Fault Tree (FT) is constructed to describe the logical relations among conditions and factors resulting in the evolvement of emergency. Given different feasible response actions, the probabilities of emergency scenarios are estimated by FTA. Furthermore, the overall ranking value of each action is calculated, and a ranking of feasible response actions is determined. Finally, a case study on H1N1 infectious diseases is given to illustrate the feasibility and validity of the proposed method.

Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens.

Knowledge concerning the clinical and biological characteristics of acute leukemia of ambiguous lineage (ALAL) is limited so that there has been a lack of uniformity in treatment. In this report, we retrospectively investigated the effect of intensified conditioning on adult ALAL undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 59 patients with ALAL (male in 37 cases and female in 22 cases) were consecutively enrolled in the data analyses. Twenty-four patients received the standard conditioning (total body irradiation (TBI) + cyclophosphamide (CY) or busulfan + CY protocol) and 35 received the intensified conditioning (TBI + CY + etoposide or fludarabine + cytarabine plus TBI + CY + etoposide protocol). Five-year transplant-related mortality was 17.6 ± 9.6 % and 25.5 ± 8.0 %, the 5-year overall survival (OS) post-transplantation was 23.8 ± 8.9 % and 64.0 ± 8.4 %, disease-free survival was 16.7 ± 7.6 % and 55.8 ± 9.4 %, the 5-year cumulative incidence of relapse was 80.8 ± 8.5 % and 28.8 ± 9.9 %, respectively, in the standard and the intensified group (P = 0.380, P = 0.029, P = 0.005, and P < 0.001). Both univariate and multivariate analysis indicated that the intensified conditioning regimen and acute graft-versus-host disease were favorable factors to reduce the relapse. The younger patients, patients with CR at the time of transplantation, and the intensified conditioning regimen were favorable factors to elevate the survival. In conclusion, intensified conditioning regimens followed by allo-HSCT might improve long-term survival and decrease relapse of leukemia in adult ALAL compared to the standard conditioning regimens.

Exploring users' content creation and information dissemination behavior in social media: The moderating effect of social presence.

Users' personality traits reveal different social media behavior characteristics. In order to explore the intrinsic relationships between personality traits and social media behavior, this study analyzes the influence of users' personality traits on social media content creation and information dissemination behavior, as well as the moderating effect of social presence. We collect users' personality data via questionnaires, crawl social media behavior data of samples from social media sites, and then establish regression models to test the research hypotheses. The results show that extraversion has a positive impact on content creation and information dissemination behavior, conscientiousness has a negative impact on content creation behavior, openness and agreeableness have no significant impact on social media behavior, and social presence has significant moderating effects on the relationships between personality traits and social media behavior.

The novel HLA-B*40:01:78 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:01:78 differs from HLA-B*40:01:02:01 by one nucleotide in exon 3.

Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study.

A total of 123 consecutive patients with advanced-stage, acute leukemia undergoing HSCT from HLA-identical sibling donors were analyzed. A G-CSF-primed DLI was planned within day 60 post-transplantation before hematologic relapse was diagnosed. Fifty of the 123 individuals received prophylactic DLI, and 73 individuals received no prophylactic treatment. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was 17% for patients receiving DLI and 23% for patients not receiving DLI (p = 0.35). The incidence of chronic GVHD was 38% for patients receiving DLI and 17% for patients not receiving DLI (p = 0.021). The two-yr cumulative incidence of relapse was significantly lower in patients who received prophylactic DLI (46%) compared with patients who did not receive prophylactic DLI (66%) (p = 0.02). The three-yr probability of overall survival was higher in patients who received prophylactic DLI (36%) than in patients who did not receive prophylactic DLI (11%) (p = 0.001). The leukemia-free survival was also higher in patients who received prophylactic DLI (29%) than in patients who did not receive prophylactic DLI (9%) (p = 0.001). Our comparisons suggest that the prophylactic use of DLI can significantly increase survival of patients with advanced-stage, acute leukemia who receive HLA-identical sibling HSCT.

[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia].

OBJECTIVE: To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1). METHODS: Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg×kg(-1)×d(-1), 7 - 4 days before transplantation; Cy 60 mg×kg(-1)×d(-1), 3 - 2 days before transplantation) and Bu/Flu (Bu 3.2 mg×kg(-1)×d(-1), 5 - 2 days before transplantation; Flu 30 mg×m(-2)×d(-1), 6 - 2 days before transplantation) groups. The regimen-related toxicity (RRT), incidence and severity of graft-versus-host disease (GVHD), 3-year cumulative relapse rate, non-relapse mortality (NRM), 3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups. RESULTS: The median follow-up duration was 617.5 (6 - 1261) days. All patients achieved successful engraftment on 30 day after transplantation. There were no significant differences in the median time to neutrophil engraftment (P = 0.121) and platelet engraftment (P = 0.171) between the two groups. The median duration of neutrophil count under 0.1×10(9)/L and platelet count under 20×10(9)/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P = 0.000 and P = 0.047). The incidence of grades II-IV RRT were 68.8% and 25.0% (P = 0.032) in the Bu/Cy and the Bu/Flu groups, respectively. There were no significant differences in the incidence of acute GVHD (P = 0.149), chronic GVHD (P = 0.149), incidence of NRM (P = 0.333), 3-year cumulative relapse rates (P = 0.834), 3-year EFS rate (P = 0.362) and OS rate (P = 0.111) between the two groups. CONCLUSION: Compared with Bu/Cy, Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.

E-commerce platform financing versus trade credit financing: Financing mode selection for online retailer considering live-stream selling in China.

Introduction: The rise of live-stream selling has made the e-commerce platform attractive to many small and medium-sized retailers that are often faced with capital constraints. The choice between the e-commerce platform financing (EPF) and trade credit financing (TCF) for the capital-constrained e-retailers engaging in live-stream selling is particularly important problem. Methods: This paper considers a supply chain made up of a manufacturer, an e-commerce platform that offers live-stream selling service to consumers and an online retailer with capital constraint. We, respectively, investigate the optimal decisions of the supply chain enterprises under EPF and TCF modes based on Stackelberg game models and optimization theories. Results: We compare the profits of supply chain firms under different cases and obtain some important conclusions through theoretical and numerical analysis. Discussion: First, when the e-commerce platform's commission rate is low enough, the retailer's ordering quantity is, under EPF mode, greater than that evidenced without capital constraint. In addition, when the retailer's marginal profit is high and the e-commerce platform's commission rate is low, the online retailer should choose EPF mode; in other instances, TCF is its optimal choice. Second, the e-commerce platform can obtain the highest profit under EPF mode, while TCF mode will bring the highest profit to the manufacturer. Third, when the platform's commission rate is below a certain threshold, the profit of the entire supply chain under EPF mode is larger than that of well-funded supply chain, but TCF mode cannot. Finally, we also find there exists the access threshold about the live-stream selling. Only when the commission rate is relatively high, the e-commerce platform should offers live-stream service to consumers and the live-stream investment is the highest under EPF mode.

Remanufacturing Strategy Choice of a Closed-Loop Supply Chain Network Considering Carbon Emission Trading, Green Innovation, and Green Consumers.

Due to increasingly serious environmental pollution problems and governments' strengthening of environmental impact supervision, manufacturing companies are seeking green production methods, implementing carbon trading systems, and promoting the trend towards green remanufacturing. Thus, this paper introduces green factors to the existing closed-loop supply chain network models and studies the impact of carbon trading, green innovation efforts, and green consumers on the choice between two remanufacturing strategies: an in-house remanufacturing strategy and an authorized remanufacturing strategy. The results concerning the choice of the remanufacturing strategy are as follows: from the perspective of obtaining more profits, when the carbon trading price is low, the companies choose the authorized remanufacturing strategy; when the carbon trading price is high, the companies choose to remanufacture by themselves. For all the green innovation efforts and the proportions of green consumers, when the recovery rate of the used product is low, the companies choose to remanufacture by themselves; when the recovery rate of the used product is high, the companies choose the authorized remanufacturing strategy.

Effect of pediatric- versus adult-type chemotherapy regimens on outcomes of allogeneic hematopoietic stem cell transplants for adult T-cell acute lymphoblastic leukemia in first complete remission.

The optimal chemotherapy regimen pre-transplantation for adult T-cell acute lymphoblastic leukemia (T-ALL) patients remains unknown. Here, we compared the transplant outcomes in 127 subjects receiving pediatric- (N = 57) or adult-type (N = 70) regimens pre-transplant. The corresponding 3-year cumulative incidences of relapse (CIR) was 7% (95% CI: 3-11%) and 29% (95% CI: 23-35%; P = 0.02), leukemia-free survivals (LFS) was 86% (95% CI: 81-91%) and 57% (95% CI: 51-63%; P = 0.003), overall survivals (OS) was 88% (95% CI: 84-92%) and 58% (95% CI: 52-64%; P = 0.002), the 1-year NRM was 4% (95% CI: 1-7%) and 9% (95% CI: 4-14%; P = 0.40). Multivariate analysis showed that pediatric-type regimen was associated with lower CIR (Hazard Ratio [HR] = 0.31 [95% CI: 0.09-1.00]; P = 0.05), better LFS (HR = 0.34 [95% CI: 0.15-0.78]; P = 0.01) and OS (HR = 0.30 [95% CI: 0.13-0.72]; P = 0.01). Our results suggested that adult T-ALL patients undergoing allo-HSCT might benefit from pediatric-type chemotherapy.

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

Long-term outcomes of HLA-matched sibling compared with mismatched related and unrelated donor hematopoietic stem cell transplantation for chronic phase chronic myelogenous leukemia: a single institution experience in China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy for chronic myelogenous leukemia (CML). In this study, the long-term outcomes of HLA-matched sibling donor (MSD) with mismatched related donor (MRD) and unrelated donor (URD) transplantation for CML in the first chronic phase (CML-CP1) using different graft vs. host disease (GVHD) prophylaxis regimens according to donor source and the degree of HLA matching were compared. The data of 91 patients with CML-CP1 were analyzed with respect to GVHD, overall survival (OS), and transplant-related mortality (TRM). The incidence of grade II-IV acute GVHD was 25.5% in the MSD and 40.5% in the MRD/URD group (P = 0.133). The 1-year cumulative incidence of chronic GVHD was not different between the MSD and the MRD/URD groups, while extensive chronic GVHD was different between the two groups (31.9% vs. 10.8%, P = 0.023). The 5-year cumulative relapse rate was not different between the MSD and the MRD/URD groups, while TRM was different between the two groups (6.6% vs. 26.3%, P = 0.010). The 5-year cumulative OS was 90.9%, 71.5%, and 85.4% in the MSD, the MRD/URD, and the HLA allele-matched URD transplantation, respectively (MSD vs. MRD/URD, P = 0.013; MSD vs. HLA allele-matched URD, P = 0.437). In conclusion, survival in HLA allele-matched URD is equivalent to MSD, but in MRD and mismatched URD is inferior to MSD in patients with CML-CP1 undergoing allo-HSCT using different GVHD prophylaxis regimens according to donor source and degree of HLA matching. Patients undergoing MRD/URD transplantation have an equal quality of life as patients undergoing MSD transplantation.

[Allogeneic hematopoietic stem cell transplantation for acute leukemias of ambiguous lineage in adults: a comparison between the conditioning of different intensities].

OBJECTIVE: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the conditioning of different intensities for acute leukemias of ambiguous lineage (ALAL). METHODS: A total of 38 ALAL patients were treated with two conditioning of different intensities in our hospital from March 2002 to August 2010. The standard conditioning included TBI + Cy or Bu + Cy, intensified conditioning included Fludarabine + Ara-C + TBI + Cy. Cyclosporine A (CsA) and methotrexate (MTX) were administered in patients with human leukocyte antigen-matched sibling donor. And CsA, MTX plus antihuman thymocyte globulin and/or mycophenolate were used in all patients with HLA-mismatched related donor and unrelated donors transplants for graft-versus-host disease (GVHD) prophylaxis. COX regression was used to evaluate the prognostic factors of ALAL. RESULTS: Among 38 ALAL patients, 19 received the standard conditioning while another 19 the intensified conditioning. All patients achieved hematopoietic reconstitution. The 5-year overall survival (OS) and the disease-free survival (DFS) were 35.5% and 25.7% respectively. The 5-year OS rates were 20.2% and 48.1% (P = 0.233) and DFS 6.5% and 43.1% (P = 0.031) in the standard and intensified conditioning groups respectively. The 5-year cumulative relapsing incidence was 58.9% in all patients and 87.6% vs 30.4% in the standard and intensified conditioning groups respectively (P = 0.003). Through a COX regression model for univariate analysis, the intensified conditioning and chronic GVHD were protective factors for DFS (P = 0.001, 0.031). CONCLUSION: The intensified conditioning in ALAL patients undergoing allo-HSCT may improve the long-term patient survival and decrease the relapse of leukemia. The graft versus leukemic effect has some efficacy in ALAL patients undergoing allo-HSCT.

[Clinical Characteristics and Prognosis of Elderly Patients with Medium and High risk Myelodysplastic Syndrome].

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with medium and high risk myelodysplastic syndrome (MDS). METHODS: 97 MDS patients above the age of 60 treated in Nanfang Hospital, Southern Medical University from February 2011 to August 2020 were enrolled. The clinical characteristics and prognosis of the MDS patients with medium risk, high risk or very high risk based on IPSS-R category were retrospectively analyzed. According to the difference of treatment regimes, the patients were divided into the transplantation group, chemotherapy group and other treatment group, and the efficacy among the patients in the 3 groups were analyzed. RESULTS: MDS with excess blast (MDS-EB) in the elderly patients with medium and high risk MDS were the most common, 47.4% of the patients with abnormal chromosome karyotypes, and 23.7% with complex karyotypes (≥3). 97.3% of the patients showed at least one gene mutation, and TP53 mutations were detected in nearly 20% of the patients with medium and high risk. Multivariate analysis showed that IPSS-R category and treatment regimes were the factors affecting the prognosis of elderly patients with medium and high risk MDS. The median overall survival (OS) time of the patients in the 3 groups showed significant difference (P=0.012), and the median OS of the patients in the transplantation group was significantly longer than that in the chemotherapy group and other group (P=0.003,P=0.014,respectively), while there was no significant difference in median OS between chemotherapy group and other treatment group (P=0.685). CONCLUSION: Elderly MDS patients with medium and high risk can benefit from allogeneic hematopoietic stem cell transplantation, which will prolong their OS.

Haploidentical donor transplant is associated with secondary poor graft function after allogeneic stem cell transplantation: A single-center retrospective study.

BACKGROUND: Secondary poor graft function (sPGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) related to poor outcome. We aimed to retrospectively evaluate the morbidity and hazard elements of sPGF after allo-HSCT. METHODS: Eight hundred and sixty-three patients who achieved initial engraftment of both neutrophils and platelets were retrospectively reviewed in this study. RESULTS: Fifty-two patients developed sPGF within 180 days post-transplants, with the median onset time was 62 days (range, 34-121 days) post-transplants. The overall cumulative incidence of sPGF within 180 days post-transplantation was 6.0%, with 3.4%, 3.4%, and 10.1%, respectively, in matched sibling donor (MSD), matched unrelated donor (MUD), and haploidentical donor (HID) transplant (p < 0.0001). Multivariable analysis showed that HID (HID vs. MSD: hazard ratio [HR] 2.525, p = 0.004; HID vs. MUD: [HR] 3.531, p = 0.017), acute graft versus host disease (aGVHD) within +30 days ([HR] 2.323, p = 0.003), and cytomegalovirus (CMV) reactivation ([HR] 8.915, p < 0.0001) within +30 days post-transplants were hazard elements of sPGF. The patients with sPGF had poorer survival than good graft function (51.7±8.1% vs. 62.9±1.9%, p < 0.0001). Our results also showed that only CMV reactivation was the hazard element for the development of PGF in HID transplant ([HR] 12.521 p < 0.0001). CONCLUSION: HID transplant is also an independent hazard element of sPGF except for aGVHD and CMV reactivation.

Wnt/ß-catenin signaling mediates the abnormal osteogenic and adipogenic capabilities of bone marrow mesenchymal stem cells from chronic graft-versus-host disease patients.

Chronic graft-versus-host disease (cGVHD) is the main cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mesenchymal stem cells (MSCs) in bone marrow (BM) remain unclear in the pathophysiology of cGVHD. In this study, we analyzed BM-MSCs from 66 patients after allo-HSCT, including 33 with active cGVHD and 33 without cGVHD. BM-MSCs showed similar morphology, frequency, phenotype, and proliferation in patients with or without cGVHD. MSCs from the active cGVHD group showed a decreased apoptosis rate (P < 0.01). Osteogenic capacity was increased while adipogenic capacity was decreased in the active cGVHD MSCs compared with no-cGVHD MSCs. The expressions of osteogenic gene RUNX2 and COL1A1 were higher (P < 0.001) while adipogenic gene PPAR-γ and FABP4 were lower (P < 0.001) in the active cGVHD MSCs than no-cGVHD MSCs. These changes were associated with the severity of cGVHD (P < 0.0001; r = 0.534, r = 0.476, r = -0.796, and r = -0.747, respectively in RUNX2, COL1A1, PPAR-γ, and FABP4). The expression of Wnt/ß-catenin pathway ligand Wnt3a was increased in cGVHD-MSCs. The dysfunction of cGVHD-MSCs could be reversed by Dickkopf related protein 1(DKK1) to inhibit the binding of Wnt3a. In summary, the differentiation of BM-MSCs was abnormal in active cGVHD, and its underlying mechanism is the upregulated of Wnt3a through Wnt/ß-catenin signaling pathway of MSCs.