G-CSF-Mobilized Blood and Bone Marrow Grafts as the Source of Stem Cells for HLA-Identical Sibling Transplantation in Patients with Thalassemia Major.

As an inherited anemia, thalassemia major (TM) is currently only curable with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here we report an allo-HSCT protocol for patients with TM who received a combination of granulocyte colony-stimulating factor-primed bone marrow and peripheral blood stem cells (G-BM & PBSCs) from a matched sibling donor (MSD). The conditioning regimen consisted of i.v. busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin. Chimerism analysis was performed for all patients. Immunosuppressive treatment was terminated if rejection was suspected, and donor lymphocyte infusion was administered once no response was observed. A total of 184 patients with TM were enrolled in the study between July 2007 and July 2018. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 13.1%, and that of moderate or severe chronic GVHD was 5.7%. The cumulative incidence of graft rejection was .6%. In the total cohort, the 3-year overall survival, thalassemia-free survival, and GVHD-free, relapse-free survival were 97.8%, 97.3%, and 89.5%, respectively. Collectively, our results indicate that G-BM & PBSCs from an MSD is be a good stem cell source for patients with TM undergoing allo-HSCT.

Immune recovery after in vivo T-cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta-thalassemia children.

BACKGROUND: The clinical outcome of hematopoietic stem cell transplantation (HSCT) in those with severe beta-thalassemia (ß-TM) is closely related to post-transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce. METHODS: A prospective analysis of the clinical outcome and IR in 47 children with severe ß-TM who underwent in vivo T-cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. Immune reconstitution, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measured. RESULTS: In the first year after HSCT, bacterial infections and cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4+ T-cell recovery was observed. The B cells recovered within 6 months. Natural killer (NK) cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB + BM) group had slower T-cell recovery, and higher B cells and NK cells in comparison with peripheral blood and bone marrow (PB + BM) group. CONCLUSIONS: The high incidence of infection within 1 year after in vivo T-cell depletion myeloablative conditioning HSCT in severe ß-TM was consistent with poor IR.

Predicting the risk of acute kidney injury after hematopoietic stem cell transplantation: development of a new predictive nomogram.

The purpose was to predict the risk of acute kidney injury (AKI) within 100 days after hematopoietic stem cell transplantation (HSCT) in patients with hematologic disease by using a new predictive nomogram. Collect clinical data of patients with hematologic disease undergoing HSCT in our hospital from August 2012 to March 2018. Parameters with non-zero coefficients were selected by the Least Absolute Selection Operator (LASSO). Then these parameters were selected to build a new predictive nomogram model. Receiver operating characteristic (ROC) curve, calibration curve, C-index, and decision curve analysis (DCA) were used for the validation of the evaluation model. Finally, the nomogram was further evaluated by internal verification. According to 2012 Kidney Disease Improving Global Guidelines (KDIGO) diagnostic criteria, among 144 patients, the occurrence of AKI within 100 days after HSCT The rate was 29.2% (42/144). The C-index of the nomogram was 0.842. The C-value calculated by the internal verification was 0.809. The AUC was 0.842, and The DCA range of the predicted nomogram was from 0.01 to 0.71. This article established a high-precision nomogram for the first time for predicting the risk of AKI within 100 days after HSCT in patients with hematologic diseases. The nomogram had good clinical validity and reliability. For clinicians, it was very important to prevent AKI after HSCT.

[Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION: The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome after hematopoietic stem cell transplantation for thalassemia major: incidence, management, and outcome.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present prospective study, we aimed to investigate the incidence, management, and outcome of VOD/SOS in patients with thalassemia major (TM) who received allo-HSCT. VOD/SOS was diagnosed and classified based on the modified Seattle criteria. The prophylactic regimen for VOD/SOS was a combination treatment of dalteparin and lipo-PGE1. VOD/SOS was managed through an approach consisting of adequate supportive measures, short-term withdrawal of calcineurin inhibitors (CNIs), and the use of methylprednisolone and basiliximab for graft-versus-host disease prophylaxis. VOD/SOS was found in 54 of 521 patients (10.4%) at a median time of 12 days after allo-HSCT. The cumulative incidence of all-grade and moderate VOD/SOS was 10.4% and 4.2%, respectively. Among the 54 VOD/SOS patients, no patient developed severe grade and died from VOD/SOS. Besides, the cumulative incidence of transplant-related mortality on day 100 for patients with or without VOD/SOS was 0% vs. 4.0% (P = 0.187), respectively, and the 3-year overall survival rates were 94.3% vs. 93.2% (P = 0.707), respectively. Collectively, we concluded that appropriate symptomatic therapy and short-term withdrawal of CNIs safely mitigated the mortality of VOD/SOS in TM patients who underwent allo-HSCT.

[Clinical and Bacteriological Analysis of Bacterial Bloodstream Infections in Patients with Acute Leukemial].

OBJECTIVE: To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients. METHODS: Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed. RESULTS: A total of 376 strains were isolated, 76.9% was Gram-negative bacterial and 23.1% was Gram-positive bacteria. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were listed as the top three of Gram-negative bacteria. The susceptibility of Escherichia coli to the tigacycline, imipenem and meropenem was 100.0%, 98.2% and 98.1%, respectively. The susceptibility of Klebsiella pneumoniae to the tigacycline, imipenem and meropenem were 100.0%, 98.3% and 94.4%, respectively. The adjustment rate for initial use of carbopenems was 3.8%, while the adjustment rate for initial use of noncarbopenems was 74.3% in patients with main Gram-negative bacterial blood stream infection. The susceptibility of Gram-positive bacteria to glycopeptide antibiotics, linezolid and tigacycline was 100.0%. CONCLUSION: Gram-negative bacteria is the majority type of bacteria in AL patients with bacteria blood stream infections. The susceptibility of Gram-negative bacteria to the carbapenems is high, and the treatment adjustment rate is obviously low. The glycopeptide, linezolid and tigacycline are effective for Gram-positive bacteria infections..

Synthesis of Chiral Piperazines via Hydrogenation of Pyrazines Activated by Alkyl Halides.

A facile method has been developed for the synthesis of chiral piperazines through Ir-catalyzed hydrogenation of pyrazines activated by alkyl halides, giving a wide range of chiral piperazines including 3-substituted as well as 2,3- and 3,5-disubstituted ones with up to 96% ee. The high enantioselectivity, easy scalability, and concise drug synthesis demonstrate the practical utility.