Purpose To evaluate the efficacy and safety of second allogeneic hematopoietic cell transplant (allo-HCT) in patients with myeloid hematologic malignancies who relapsed or encountered graft failure after the first allo-HCT. Patients and Methods This retrospective analysis included 12 cases with acute myeloid leukemia or myelodysplastic syndrome who underwent a second allo-HCT at Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital between January 2020 and May 2024. There were 8 male and 4 female, the median age at was 40.5 (18-56), 9 patients with acute myeloid leukemia and 3 cases with myelodysplastic syndrome. Donor at first allo-HCT: 10 from related haploidentical donor, and 2 from matched sibling donor. 7 cases used a different donor for second allo-HCT: 2 matched unrelated donor, 1 matched sibling donor, 4 related haploidentical donor. The performance status assessment by ECOG score were：1 case scored 0, 1 case scored 1, 6 cases scored 2, 3 cases scored 3, 1 case scored 4. As for Hematopoietic Cell Transplantation-Comorbidity Index(HCT-CI) score：10 cases scored 1，1 case scored 2 and 1 case scored 3. The time interval between two allo-HCT: 4 cases within 180 days，8 cases beyond 180 days. Strongly positive DSA were detected in 2 cases. The disease status assessment before second allo-HCT: only 4 cases were in complete remission. Conditioning regimen: 3 patients encountering graft failure received reduced intensity conditioning, while 9 relapsing patients received total body irradiation (8Gy) and thiotepa (5mg/kg for 2 days) based myeloablative conditioning. GVHD prophylaxis included porcine anti human lymphocyte immunoglobulins, tacrolimus, methotrexate and/or anti-CD25 antibody. Our primary endpoint was OS, defined as time from transplantation to 1 year and last follow-up post-HCT or date of death. Statistical analyses were performed using the statistical package SPSS version 17. Results Engraftment was achieved in 10 patients (including those 2 cases with strongly positive DSA), the median time of neutrophil engraftment was 10(9-16) days. 2 patients died on +4 and +8 day after second allo-HCT, were excluded from further analysis. 10 patients were in complete remission by day 30 post second allo-HCT, no relapse were detected during the follow up. The median follow up was 364 (72-1007) days. 5 patients died and the other 5 survived by 2024.9.30, causes of death including severe pneumonia, multiorgan failure, and severe GVHD. The median overall survival was 535(95%CI:339-730)days, the 1 year cumulative survival rate was 78%，and the 2 year cumulative survival rate was 35%. Univariate analyses suggested ECOG (＞2) and HCT-CI(＞1) score were correlated with patient survival after second allo-HCT. Conclusion The findings of our current study indicate that a second allo-HCT is a reasonable treatment choice for AML and MDS patients relapsing or encountering graft failure after a first allo-HCT, complete response and survival benefit may be anticipated particularly in those with better performance status and fewer comorbidities.

PTCL are a heterogeneous group of lymphoproliferative disorders generally associated with dismal clinical outcomes, especially in the R/R context. Allo-SCT as the potentially curative therapeutic option for R/R PTCL patients, fails to provide lasting tumor control. Our previous research has confirmed that an ATG-based conditioning regimen is a feasible and effective alternative for patients with aggressive TCLs. A retrospective analysis was conducted on patients with advanced R/R PTCL who underwent allo-SCT at our center. All the patients treated with the TBI-ATG-based myeloablative conditioning regimen. Thirty-seven R/R PTCL patients, with a median age of 51 years at transplantation, were analyzed. All patients had experienced relapse or primary progression of T-cell lymphoma prior to allo-SCT. Specifically, 5 patients had achieved PR in response to their last salvage treatment and 32 patients had PD at the start of conditioning for allo-SCT. All patients successfully engrafted and achieved full donor chimerism. At a median follow-up of 25.8 months, the 2-year OS and PFS were 61.69% and 58.73%, respectively. Thirty-one cases underwent haplo-allo-HSCT. The 2-year OS and PFS for this subgroup were 68.09% and 58.34%, respectively. Five cases who achieved PR prior to allo-SCT, with a median follow-up of 38.5 months, all are alive and disease-free. Additionally, in the subgroup of 32 cases who were in PD status prior to allo-SCT, the 2-year OS and PFS were 54.89% and 50.77%, respectively. The 2-year relapse rate (RR) was 31.59% and 2-year relapse-related mortality (RRM) was 16.95%. The 2-year NRM was 25.53%.

Objective:To investigate the efficacy and safety of a treatment regimen combining Daratumumab(Dara)with Venetoclax(Ven)in patients suffering from relapsed/refractory T-lymphoblastic leukemia/lymphoma(T-ALL/LBL).Methods:From January 2023 and January 2024,twelve patients with relapsed/refractory T-ALL/LBL received a combined treatment regimen based on Dara and Ven.The cohort consisted of 9 males and 3 females,with a median age of 25(range:15-57)years.Within each 28-day treatment cycle,Dara was scheduled to administer at a dosage of 16 mg/kg once weekly for 4 weeks,while Ven was given at 400 mg daily for 21 days,within each 28-day cycle.Additionally,some patients received liposomal mitoxantrone and pegaspargase as part of their treatment.Results:The combined regimen of Dara and Ven achieved an overall response rate(ORR)of 75.0％,with a complete remission(CR)rate of 58.8％.Among the 12 patients,seven had not previously undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT).Of these,four achieved CR,one a-chieved partial remission(PR),and two did not respond.Of the four CR patients who subsequently underwent allo-HSCT as consolidation therapy,three remained disease-free,while one relapsed.The PR patient and one non-remission(NR)patient died due to disease progression after different chemotherapy regimens.Another NR patient died early after salvage transplantation due to infection.Five patients were enrolled post-allo-HSCT.Four of them relapsed after the first transplantation,and one developed a secondary neoplasm.Among these,three pa-tients(60.0％)achieved CR,with two remaining disease-free;one relapsed and underwent a second allo-HSCT.Of the other two patients,one achieved PR,and one failed to respond.Both of them died due to disease progres-sion.For all 12 patients,the one-year overall survival(OS)was 58.3％(95％CI 27.0％-80.1％),and the median survival was not reached.The one-year progression-free survival(PFS)of 9 patients who achieved response was 53.3％(95％CI 17.7％-79.6％),The one-year OS for the 5 patients after transplantation was 60.0％(95％CI 12.6％-88.2％),and the PFS of 4 responded patients was 50.0％(95％CI 5.8％-84.5％).Only 2 patients expe-rienced infusion reactions related to Dara with no serious treatment-related adverse events.Conclusion:The Dara and Ven regimen demonstrate a high response rate and well-tolerated treatmnet option for patients with relapsed/refractory T-ALL/LBL.It can serve as a bridging treatment for patients who have not undergone allo-HSCT.For patients who experience relapse after allo-HSCT,it can also be used as a maintenance therapy to extend disease-free survival.

Our study includes 103 patients aged between 51 and 60 years who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling donors (MSDs) (n = 36), haploidentical donors (HIDs) (n = 56), and unrelated donors (URDs) (n = 11). Multivariate analysis exploring the relationship between risk factors and survival confirmed that survival outcomes were only independently impacted by Eastern Cooperative Oncology Group (ECOG) score (ECOG scores ≥2 vs. ECOG scores of 0-1, overall survival [OS] HR: 2.91 [95% CI 1.35-6.27], p = 0.006; failure free survival [FFS] HR: 2.93 [95% CI 1.33-5.88], p = 0.006; graft-versus-host disease-free/relapse-free survival [GRFS] HR: 2.80 [95% CI 1.33-5.88], p = 0.006), while age, specific donor source and hematopoietic cell transplantation-comorbidity index (HCT-CI) score did not significantly influence prognosis in this age group. After applying propensity score-matching (PSM) to balance the pretransplant clinical factors between patients with ECOG scores 0-1 cohort and those with ECOG scores ≥2 cohort, poor performance status remains a negative factor for survival outcomes (OS p = 0.04; FFS p = 0.03; GRFS p = 0.03). Further analysis in subgroup patients with HCT-CI scores 0-1 found the retained significance of ECOG score in predicting inferior survival. In conclusion, our results indicate good long-term results of allo-HSCT in elderly SAA adults regardless of donor type. Higher ECOG score is associated with poor post-transplant outcomes and has to be taken into account for patients, even at a low-risk comorbidly burden.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient’s complete remission has persisted for 20 months after HSCT.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) serves as a critical therapeutic approach for various malignant and non-malignant hematopoietic disorders. Notwithstanding successful hematopoietic recovery in most patients following allo-HSCT, a subset may encounter delayed platelet engraftment (DPE), a prevalent and potentially serious complication that stems from myeloablative conditioning. Occurring in approximately 5%-37% of allo-HSCT recipients, DPE is a known harbinger of increased transplant-related mortality and diminished quality of survival. Despite its clinical significance, a well-established standard treatment protocol for post-allo-HSCT DPE remains elusive. Multiple platelet transfusions, often administered in such cases, not only exacerbate the economic burden but also induce toxicities, thereby undermining the patient's quality of life. An alternative to platelet transfusion lies in the utilization of thrombopoietin-receptor agonists (TPO-RAs), advocated for enhancing platelet engraftment. These agents interact with the thrombopoietin receptor, stimulating intracellular signaling pathways inclusive of JAK/STAT, PI3K/AKT, and ERK1/2, which in turn, promote megakaryocyte proliferation and differentiation, thereby augmenting platelet production. Hetrombopag, a novel, orally administered, non-peptide, small-molecule TPO-RA, has been validated to effectively boost platelet engraftment and reduce the necessity for platelet transfusions post-allo-HSCT in a pilot study. Our study sought to investigate the effectiveness and safety of hetrombopag in treating DPE following allo-HSCT within a real-world setting. Methods: In this retrospective study, we evaluated adult patients with hematopoietic disorders who underwent allo-HSCT and subsequently experienced DPE in our center, treated with hetrombopag between March 2022 and April 2023. Given the lack of a consensus definition, we deemed DPE as a platelet count (PLT) < 20 × 10 9/L or a significant and rapid decreasing trend past day 28 post-allo-HSCT. Hetrombopag dosages of 2.5 mg, 5 mg, or 7.5 mg/day were prescribed based on individual patient conditions. Response criteria post-treatment were as follows: complete response: PLT > 50 × 10 9/L without platelet transfusion; partial response: PLT between 20 and 50 × 10 9/L without platelet transfusion; no response: PLT < 20 × 10 9/L. Results: A total of 20 patients were included in the analysis, with a median age of 52, and 60% of them were male. Hetrombopag administration commenced at a median of 58 days following allo-HSCT at a median dose of 5 mg/day, with a median treatment duration of 44 days. The initial platelet count was 24.5 × 10 9/L and serum ferritin levels stood at 3351.1 ng/mL. Post-hetrombopag treatment, platelet counts escalated to 67.5 × 10 9/L while serum ferritin levels decreased to 2726.0 ng/mL. Of the 20 patients, 13 patients (65%) exhibited a complete response, 6 patients (30%) achieved a partial response, and 1 patient (5%) displayed no response. Hetrombopag was well tolerated with only 5 patients reporting increased alanine aminotransferase/aspartate aminotransferase or total bilirubin levels (all grade 1 or 2), and the association with hetrombopag was undetermined. Conclusion: Our findings suggest that hetrombopag yields a sustained response with acceptable tolerability in patients who experienced DPE following allo-HSCT, and could potentially offer a novel approach for managing such patients. Future large-scale, prospective studies are warranted to further assess the potential benefits of hetrombopag for improving patient outcomes following allo-HSCT.

Objective: Immunosuppression intensified conditioning regimen has been applied for 10 patients with strong positive pre-transplantation Donor specific Anti-HLA Antibodies (DSAs) undergoing Haploidentical Hematopoietic Stem Cell Transplantation (HSCT), its effects on engraftment of hematopoietic stem cell were examined. Methods: Characteristics of 10 consecutive patients with strong positive pre-transplantation DSAs were retrospectively analyzed, including gender, age, diagnosis, disease status pre-transplantation, presence of DSA, conditioning regimens, engraftment, graft versus host disease (GVHD) incidence and survival. Results: Ten patients [3 males vs 7 females, median age 53.5(36-64)] received immunosuppression intensified conditioning regimen: Fludarabine plus busulfan (FluBu) combining total body irradiation and cyclophosphamide (TBI-Cy). DSA levels gradually decreased in all patients after preparative conditioning, and the mean fluorescence intensity (MFI) values dropped significantly (P＜0.003). The average MFI values dropped 40% at day 7 post-HSCT, 8 cases acquired hematopoietic reconstitution, the median time of neutrophil engraftment was 15.6(10-16) days, and 19(13-22) days for platelet engraftment. One case had primary graft failure and another one had poor graft function. After a median follow-up of 12.5(1.5-27) months, 7 cases remained in disease remission state with negative DSA assay, including 2 cases with MFI values higher than 20000 pre-transplantation. Conclusions：Immunosuppression intensified conditioning regimen can efficiently decrease the Donor specific Anti-HLA Antibodies (DSA) level, which leads to lowered chances of primary graft failure.

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Objectives: To investigate the efficacy of short-term substitution of Recombinant humanized anti-CD25 monoclonal antibody (anti-CD25 rhMAb) as aGVHD prophylaxis in CNIs intolerant patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Methods: From August 2021 to August 2022, seventeen patients with refractory hematologic malignancies after salvage Allo-HSCT were enrolled in our study. All were treated with anti-CD25 rhMAb as GVHD prophylaxis due to severe CNIs intolerance such as acute renal dysfunction, central nervous system complications (CNSC) or endothelial injury syndromes. There were seven males and ten females, with a median age of 43 years (18-67). After the withdrawal of CNIs, anti-CD25 rhMAb was applied at 1mg/Kg once a week until the reinstitution of CNIs or mTOR inhibitors. Results: Anti-CD25 rhMAb was initiated at a median of 5 days (range: 1-32) after HSCT. The median duration of substitution was 20(7-120) days. All achieved neutrophil engraftment after a median of 12 days (range: 10-17). Thirteen patients had platelet engraftment after a median of 13 days (range: 11-20). Four patients did not achieve stable platelet engraftment. Eight patients (47.1%) developed Grade II-IV aGVHD, and four (23.6%) developed Grade III-IV aGVHD. Only one patient died of aGVHD. Until December 31, 2022, Seven of 17 patients died. The longest follow-up time of the survivors was 347 days, and the median survival was not reached. Overall survival (OS) at six months was 62.6%. OS at six months was 80.0% in the subgroup with CNSC. Conclusions: When CNIs intolerance occurs during Allo-HSCT, Short-term replacement of CNIs with anti-CD25 rhMAb is an optional approach, which may provide a promising aGVHD prophylaxis for patients with CNIs intolerance.

Objectives: To evaluate the clinical outcomes and safety of haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT)with total body irradiation (TBI)/rabbit Anti-thymocyte globulin (rATG) based conditioning regimen in chemotherapy-resistant advanced-stage peripheral T-cell lymphoma (PTCL). Methods: From September 2019 to December 2022, eleven chemotherapy-resistant advanced-stage PTCL patients who underwent haplo-HSCT were enrolled in our study. All of them received TBI/rATG-based conditioning regimen in our centers. Results: ①Among 11 patients, there were 6 males and 5 females with a median age of 40(range：22~58) years old. Six cases of them are peripheral T-cell lymphoma not otherwise specified (PTCL NOS), 3 cases are angioimmunoblastic T-cell lymphoma (AITL), 1 case is large-cell transformation of mycosis fungoides (MF-LCT), and 1 case is T-cell large granular lymphocytic leukemia(T-LGLL). The Lugano stage was III or IV in all cases, and 8 patients had B symptoms. The median number of previous chemotherapy exposure before transplantation was 4 (range: 2~10) lines and the disease status before transplantation was progressive diseases (PD) in all cases. The median time from diagnosis to transplantation was 17(range：6~36) months.②The conditioning regimen consisted of TBI 2Gy d-8, 4Gy from day-7 to -6, rATG 2.5 mg/kg/d day-5 to -2, etoposide 15mg/kg/d day-5 to -4, cyclophosphamide (CTX) 50mg/kg/d, day-3 to -2. The patients with central nervous system involvement received a regimen of thiotepa 5 mg/kg/d， from day -5 to -4 instead of CTX and etoposide, and add 2.0 g/m2 of cytarabine twice a day, from day -3 to day -2 into the conditioning.③All patients were successfully engrafted. Only one patient developed Grade III-IV acute graft-vs-host disease (aGvHD). Among the 8 survivors, 4 cases developed chronic graft-vs-host disease (cGvHD).④After transplantation, CR was obtained in 9 patients. ⑤Regimen related toxicities: all were non-fatal. Hematopoietic suppression occurred in all patients after conditioning. Three patients had diarrhea and four had mucositis and three had elevated transaminase/bilirubin levels. Seven patients had infections.⑥The 1-year cumulative non-relapse mortality (NRM) and 1-year cumulative incidence of relapse (CIR) was 22.5±14.0% and 20.2±12.7%, respectively. The 1-year overall survival (OS) and 1-year disease-free survival (DFS) was 72.7±13.4% and 63.6±14.5%, respectively Conclusions: TBIand rATG based conditioning regimen is effective and safe for haplo-HSCT in chemotherapy-resistant advanced-stage PTCL.

目的:评估难治性弥漫大B细胞淋巴瘤(DLBCL)患者接受自体移植和靶向CD19的嵌合抗原受体T细胞(抗CD19 CAR-T)治疗后的疗效和安全性.方法:纳入7例疾病进展的难治性ⅣB期DLBCL患者进行自体移植,自体干细胞回输后第4天回输自体共刺激因子为4-1BB的抗CD19 CAR-T细胞2.0×106/kg(1.0×106/kg～2.6×106/kg).结果:中位随访时间186(112～326)d,最佳疗效为3例达完全缓解,4例达部分缓解,总体反应率达100％.其中巨块型的最佳疗效均为部分缓解.随访终点总生存率71.4％,其中巨块型者总生存率66％,非巨块型者总生存率75％.中性粒细胞植入时间17(14～26)d.CAR-T开始扩增的时间与中位粒细胞植入时间呈正相关(r=0.884,P=0.008).巨块型患者中CAR-T峰值出现的时间较非巨块型者晚(r=0.864,P=0.012).细胞因子释放综合征发生率28.6％(2/7),无严重细胞因子释放综合征发生.结论:自体移植联合抗CD19 CAR-T方案可作为难治性DLBCL拯救性治疗的方法.

目的:探讨去除第11天甲氨蝶呤(methotrexate,MTX)急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)预防方案在同胞相合供体异基因外周血造血干细胞移植(allogeneic peripheral blood stem cell transplantation,allo-PBSCT)中的疗效和安全性.方法:回顾性分析2015年1月至2017年8月接受同胞相合allo-PBSCT治疗的32例患者临床资料,GVHD预防方案为环孢素(CsA)联合MTX 15 mg/m2第1天,10 mg/m2第3、第6天.结果:中位随访时间14(7,30)个月,32例患者移植后全部造血重建.可评估患者中性粒细胞和血小板中位植入时间分别为13(11,18)d和16.5(14,36)d.aGVHD总体发生率为40.6％,Ⅱ～Ⅳ度aGVHD为25.0％.慢性GVHD(cGVHD)总体发生率为48.3％,其中轻度13.8％,中度20.7％,重度17.2％.移植后30 d内口腔黏膜炎的发生率为40.6％,Ⅲ～Ⅳ度口腔黏膜炎的发生率为18.8％.相比采用标准MTX预防方案的研究结果,重度口腔黏膜炎发生率显著降低(P＜0.05),而aGVHD发生率差异无统计学意义.结论:去除第11天MTX预防方案相比标准4次方案,不增加Ⅱ～Ⅳ度aGVHD发生率,口腔黏膜炎发生率明显下降.

Background:Bacterial infections are very common among patients with hematological diseases. Scant data are available regarding differences in the epidemiology and biological features of bacterial infections in neutropenic and non-neutropenic patients. Methods:The aim of this survey was to compare the bacterial pathogens in neutropenic and non-neutropenic patients in the same ward during an 8-year period. Results:A total of 1139 bacterial strains were isolated from 1071 patients with hematological diseases. The percentage of Gram-negative bacteria was significantly higher in neutropenic patients than in non-neutropenic patients (70.4% vs. 55.0%, respectively, P < .01). In neutropenic patients, the most commonly-isolated bacterium was Pseudomonas aeruginosa, followed by Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Stenotrophomonas maltophilia. In respiratory exudates, Gram-negative bacteria were also more frequently isolated from neutropenic patients than from non-neutropenic patients (79.1% vs. 56.1%, respectively, P < .01). The proportion of non-fermentative Gram-negative bacilli was significantly higher in neutropenic patients than in non-neutropenic patients (52.9% vs. 30.5%, respectively, P < .01). In blood culture samples from neutropenic patients, the most frequently identified pathogens, apart from coagulase negative staphylococcus, were Gram-negative bacilli (58.2%). In addition, the proportion of Escherichia coli in neutropenic patients was significantly higher than that in non-neutropenic patients (P < .01). Escherichia coli and Klebsiella pneumoniae strains from neutropenic patients also produced extended-spectrum β-lactamases at a higher rate of than those strains from non-neutropenic patients (Escherichia coli, 57.6% vs. 30.3%, respectively, P < .01; Klebsiella pneumonia, 31.9% vs. 13.0%, respectively, P < .01). Conclusions:This study showed that there are significant differences in the epidemiology and biological features of bacteria isolated from neutropenic and non-neutropenic patients.

Nowadays, the most wildly used regimens for graft-versus-host disease (GvHD) prophylaxis in haplo-hematopoietic stem cell transplantation (Haplo-HSCT) are based on in vivo T-cell depletion (TCD) with anti-thymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCy). To improve the efficiency of GvHD prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood (Haplo-PBSCT-Cord), a novel regimen, which is composed of low dose of ATG (5 mg/kg) and low-dose PTCy (50 mg/kg) for GvHD prophylaxis, was evaluated in a prospective phase II clinical trial (Clinicaltrials.org NCT03395860). Thirty-two patients diagnosed with hematological malignancies were enrolled in this trial. All patients received myeloablative conditioning regimens except for three patients. The cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD were 19.4% (95% CI, 5.5−33.3%) and 6.9% (95% CI, 0−16.3%) by day 100, respectively. The 1-year probability of relapse, disease free survival (DFS) and overall survival (OS) was 25.1% (95% CI, 7.3−42.9%), 59% (95% CI, 33.3−84.7%) and 78.4% (95% CI, 63−93.8%), respectively. The CIs of CMV and EBV reactivation by day 180 were 37.5% (95% CI, 19.8−55.2%) and 40.6% (95% CI, 22.6−58.6%), respectively. The results suggested that low-dose ATG with low-dose PTCy as GvHD prophylaxis in Haplo-PBSCT-Cord had promising activity.

The present study aimed to investigate the anti-tumor effect of citrate on acute monocytic leukemia (AML) and its mechanisms. The apoptosis of the AML cell line, U937, was assessed by MTT and Hoechst staining, the expression of Bcl-2, caspases-3 and -9, hypoxia-inducible factor 1α (HIF‑1α) and its target gene GLUT-1, were assayed by western blotting and the role of HIF‑1α was evaluated through siRNA. The results showed that citrate inhibits the expression of Bcl-2, while it induces the activation of caspases-3 and -9. In addition, citrate induces U937 apoptosis in a dose- and time-dependent manner by regulating the expression of HIF‑1α and its downstream target GLUT-1. The results suggest that citrate performs an anti-acute monocytic leukemia action by targeting HIF‑1α signaling and may be a promising clinical approach.

The possibility of antileukemic activity of antithymocyte globulin (ATG) was investigated in 8 human leukemic cell lines and primary leukemic cells from 15 leukemia patients. The study demonstrated that ATG induced apoptosis and reduced proliferation in both cell lines and primary leukemic cells, particularly in lymphatic origin cells, indicating that ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin.Background: Polyclonal ATGs are currently used to prevent graft-versus-host disease in allogeneic stem cell transplantation patients and to treat patients with severe aplastic anemia. It contains antibodies against antigens expressed on various hematopoietic cells, we hypothesized that it induces cell death not only in healthy cells but also in malignant hematopoietic cells. Materials and Methods: In this study, several human leukemic cell lines and primary leukemic cells from 15 patients with leukemia were used to investigate the ability of polyclonal ATGs to induce apoptosis and proliferation. Results: Polyclonal ATGs induced cell apoptosis in primary leukemic cells and in cell lines in a dose-dependent manner, and induced apoptosis in different populations through a variety of targets. Cell proliferation was significantly reduced in the presence of polyclonal ATGs; it arrested cells in the G0-G1 phase by cell cycle analysis. Treatment with polyclonal ATGs plus complement increased cytolysis of the leukemic cells; complement augments polyclonal ATG-induced leukemic cell death. Conclusion: These data show that polyclonal ATG has broad-spectrum antileukemic activity, especially for cells of lymphatic origin, as it induced cell death through a variety of targets. This study provides an experimental basis for the application of polyclonal ATGs in allogeneic hematopoietic stem cell transplantation and in patients with lymphatic leukemia.

Complement dependent cytotoxicity (CDC) significantly contributes to Rituximab (RTX) and Ofatumumab (OFA) efficacies in the treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Human CD59 (hCD59) is a key complement regulatory protein that restricts the formation of the membrane attack complex and thereby inhibits CDC. hCD59 is an important determinant of the sensitivity of NHL and CLL to RTX and OFA treatment. Recently, we developed a specific and potent hCD59 inhibitor, His-tagged ILYd4, which consists of 30 amino acid sequences extending from the N-terminus of ILYd4. Our previously published results indicate that His-tagged ILYd4 can be used as a lead candidate to further develop a potential therapeutic adjuvant for RTX and OFA treatment of RTX-resistant NHL and CLL. However, these studies were conducted using ILYd4 tagged on the N-terminus with 30 additional amino acids (AA) containing 6 X His used for immobilized metal affinity chromatograph. As a further step towards the development of ILYd4-based therapeutics, we investigated the impact of the removal of this extraneous sequence on the anti-hCD59 activity. In this paper, we report the generation and characterization of tag-free ILYd4. We demonstrate that tag-free ILYd4 has over threefold higher anti-hCD59 activities than the His-tagged ILYd4. The enhanced RTX-mediated CDC effect on B-cell malignant cells comes from tag-free ILYd4's improved functionality and physical properties including better solubility, reduced tendency to aggregation, and greater thermal stability. Therefore, tag-free ILYd4 is a better candidate for the further development for the clinical application.