[Single non-blood-related umbilical cord blood transplantation using a reduced-intensity conditioning regimen for the treatment of severe aplastic anemia].

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

[Unrelated cord blood stem cell transplantation for high-risk/refractory childhood acute myeloid leukemia: a clinical analysis of 160 cases].

Objective: To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) . Methods: Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) . Results: The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95%CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95%CI 20.0%-35.0%) and 22.4% (95%CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95%CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95%CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95%CI 62.7%-77.8%) and 72.2% (95%CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95%CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% (P=0.001) , and the 5-year OS rates were 79.9% (95%CI 70.3%-86.7%) , 71.1% (95%CI 50.4%-84.4%) and 52.9% (95%CI 33.0%-69.3%) (χ(2)=7.552, P=0.020) , respectively. Conclusions: For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.

[Efficacy and safety of ruxolitinib in the salvage treatment of chronic graft versus-host disease].

Objective: To investigate the efficacy and safety of low-dose Ruxolitinib in the treatment of patients with chronic graft-versus-host disease (cGVHD) and refractory to the first-line and/or second-line drugs after allogeneic hematopoietic stem cell transplantation. Methods: The clinical data was retrospectively analyzed of patients diagnosed with cGVHD in Anhui Provincial Hospital from July 9, 2018 to May 23, 2019. They were refractory to first-line and second-line drugs and were given a low-dose of Ruxolitinib (a dose of 5 mg twice daily if body weight ≥ 25 kg and 2.5 mg twice daily if body weight<25 kg). There was 2.5 mg reduction per week or every two weeks if the condition improved until withdrawal. The efficacy and safety of Ruxolitinib were retrospectively analyzed weekly or biweekly. If the condition improved, the dosage would be reduced by 2.5 mg weekly or biweekly until discontinuance. Results: A total of 47 patients were included in the study,and the median time of taking Ruxolitinib was 55 (21-154) days. The median time of taking effect was 14(7-28) days. The overall response rate was 87.2% (41/47). The complete response rate was 63.8% (30/47) and the partial response rate was 23.4%(11/47). Among them, 13 cases were mild and the overall response rate was 100%(13/13). Twenty one cases were moderate and the overall response rate was 90.5%(19/21). Thirteen cases were severe and the overall response rate was 69.2%(9/13). The highest overall response rate of all organs the was 100% in the gastrointestinal tract (7/7), and it was 95.8%(23/24) for the skin, 83.3%(5/6) for the liver and 76.9%(10/13) for the lung. The highest rate of complete organ response was 95.8% for skin. Eight patients (17%) developed cytopenia, of which 2(4.2%) were with a decrease of 3-4 degree hemoglobin. Recrudescence of cytomegalovirus occurred in 3 patients (6.4%). After withdrawal of Ruxolitinib, 6 patients (12.7%) had recurrence of cGVHD. The median time to relapse was 35.5(7-90) days. All of their conditions were improved after addition of Ruxolitinib. The median time of response was 7(5-14) days. The median follow-up was 208(33-412) days. Three patients(6.4%) died, and all of them died of severe pulmonary infection. Three patients (6.4%) had relapse of primary disease. The 6-month overall survival rate was 95.7%. Conclusion: Low-dose Ruxolitinib has good efficacy and safety in the treatment of cGVHD.

[Effect of KIR/HLA receptor-ligand mode on prognosis of single unrelated cord blood transplantation in patients with hematological malignancies].

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.

[Comparison of umbilical cord blood transplantation and hematopoietic stem cell transplantation from HLA-matched sibling donors in the treatment of myelodysplastic syndrome-EB or acute myeloid leukemia with myelodysplasia-related changes].

Objective: To compare the clinical efficacy of umbilical cord blood transplantation (UCBT) and hematopoietic stem cell transplantation from HLA-matched sibling donors (MSD-HSCT) in the treatment of myelodysplastic syndrome-EB (MDS-EB) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) . Methods: A cohort of 64 patients (including 38 cases of MDS-EB and 26 cases of AML-MRC) who received UCBT/MSD-HSCT from February 2011 to December 2017 were retrospectively analyzed. Results: ①Compared with MSD-HSCT group, UCBT group had a higher proportion of AML-MRC patients [52.8% (19/36) vs 25.0% (7/28) , P=0.025], and a lower median age [13 (1.5-52) years vs 32 (10-57) years, P=0.001]. ②The engraftment of neutrophils both in UCBT and MSD-HSCT groups on +42 d was 100%, and the median engraftment time was 17.5 (11-31) d and 11.5 (10-20) d, respectively. The engraftment of platelet at +100 d in UCBT group was 91.4%, the median engraftment time was 40 (15-96) d; The engraftment of platelet at +100 d in MSD-HSCT group was 100%, and the median engraftment time was 15 (11-43) d. ③There were no statistically significant differences in terms of the cumulative incidence of Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD of 100 d and transplant related mortality (TRM) of 180 d, relapse rate, overall survival (OS) , disease-free survival (DFS) between UCBT and MSD-HSCT groups (P>0.05) . ④The 3-year cumulative incidence of chronic GVHD (cGVHD) and severe chronic GVHD in UCBT group were lower than of MSD-HSCT group [28.3% (95%CI 13.4%-45.3%) vs 67.9% (95%CI 46.1%-82.4%) , P=0.002; 10.3% (95%CI 2.5%-24.8%) vs 50.0% (95%CI 30.0%-67.1%) , respectively, P<0.001]. The cumulative 3-year incidence of GVHD-free and relapse-free survival (GRFS) of UCBT group was significantly higher than of MSD-HSCT group [55.0% (95%CI 36.0%-70.6%) vs 28.6% (95%CI 13.5%-45.6%) , P=0.038]. Conclusion: UCBT could obtain better quality of life after transplantation than MSD-HSCT in treatment of MDS-EB/AML-MRC.

[Efficacy analysis of unrelated cord blood transplantation in the treatment of refractory and relapsed adult acute leukemia].

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×107/kg (by weight), the median CD34+ cells was 1.60 (0.63-3.04)×105/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.

[Comparison of unrelated cord blood transplantation and HLA-identical sibling peripheral blood stem cell transplantation for the treatment of adult hematological malignancies].

Objective: To compare the efficacy of unrelated cord blood transplantation (UCBT) and HLA-identical sibling peripheral blood stem cell transplantation (PBSCT) for the treatment of adult hematological malignancies. Methods: From April 2011 to December 2015, a total of 81 patients receiving single-unit UCBT and 57 patients receiving HLA-identical sibling PBSCT were enrolled in this study. All of the patients received myelablative conditioning. Cyclosporine combined with mycophenolate mofetil was adopted for GVHD prophylaxis. Results: The cumulative incidence of neutropil engraftment at day-42 was 95.0% and 100% in UCBT and sibling PBSCT groups, respectively (P=0.863) . Platelet engraftment at day 100 was 87.3% (95%CI 76.8%-93.1%) in UCBT group, which was significantly lower than that of sibling PBSCT group[98.2% (95%CI 87.3%-99.7%) ] (P=0.005) . There were no significant differences in terms of Ⅱ-Ⅳ acute GVHD or Ⅲ-Ⅳ acute GVHD in two groups (P=0.142, 0.521) . The 3-year chronic GVHD and extensive chronic GVHD were 14.9% (95%CI 5.2%-23.5%) and 11.2% (95%CI 2.9%-18.7%) , respectively in UCBT group, which was significantly lower than that of sibling PBSCT group[35.2% (95%CI 19.4%-47.8%) , 31.4% (95%CI 16.2%-43.9%) ] (P=0.008, 0.009) . The 3-year transplant-related mortality (TRM) was similar between two groups (30.1% vs 23.2%, P=0.464) . The relapse rate at 3-year in UCBT group[12.9% (95%CI 6.6%-21.5%) ]was significantly lower than that in sibling PBSCT group[24.3% (95%CI 13.5%-36.8%) ] (P=0.039) . There were no significant differences in terms of overall survival (OS) and disease-free survival (DFS) between two groups (58.6% vs 54.8%, P=0.634; 57.0% vs 52.4%, P=0.563) . But GVHD-free and relapse-free survival (GRFS) in UCBT group [55.7% (95%CI 44.1%-65.8%) ]was significantly higher than that of sibling PBSCT group[42.9% (95%CI 29.8%-55.3%) ] (P=0.047) . Conclusions: For adult hematological malignancies, the incidences of acute GVHD and TRM were similar between UCBT and sibling PBSCT recipients, and the incidences of chronic GVHD and relapse were lower in UCBT recipients. UCBT recipients had higher GRFS rate although OS and DFS were similar between two groups, which may reflect the real recovery and better quality of life following UCBT.

Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML.

Few studies have presented a comparison of myeloablative cord blood transplantation (CBT) and HLA-identical sibling hematopoietic cell transplantation (HCT) for AML in a disease-specific analysis, and the evaluation of GvHD-free and relapse-free survival (GRFS) in AML patients after unrelated CBT has not been reported. A total of 162 consecutive AML patients receiving intensified myeloablative unrelated CBT (n=107) or allogeneic PBSC transplantation (allo-PBSCT) or bone marrow transplantation (BMT) from an HLA-identical sibling donor (n=55) were investigated. Neutrophil or platelet engraftment was slower in the CBT cohort compared with that in the allo-PBSCT/BMT cohort. The incidence of grade II-IV or grade III-IV acute GvHD (aGvHD) and transplant-related mortality (TRM) were not significantly different in the two cohorts. Compared with the allo-PBSCT/BMT cohort, the CBT cohort had a significantly lower rate of chronic GvHD (cGvHD) (13.7% vs 28.3%; P=0.047) or extensive cGvHD (9.9% vs 24.1%; hazard ratio (HR)=2.06, P=0.039). The incidence of relapse at 5 years in the CBT cohort was significantly lower than that in the allo-PBSCT/BMT cohort (15.3% vs 36.1%; HR=4.62, P=0.009). The probabilities of overall survival and leukemia-free survival were similar between the two cohorts. The adjusted 5-year probability of GRFS was higher after CBT than that after allo-PBSCT/BMT (55.4% vs 39.2%; HR=1.63, P=0.042). The present study suggests that, for AML patients, intensified myeloablative unrelated CBT is associated with less cGvHD and a lower risk of relapse. In addition, these patients do not experience excessive TRM or severe aGvHD that translates into better GRFS compared with those patients who undergo HLA-identical sibling allo-PBSCT/BMT; this observation may reflect the clinical separation between cGvHD and GvL within our CBT protocol.

[Comparison of intensified myeloablative conditioning regime without antithymocytic globulin (ATG) with myeloablative conditioning regime for single-unit unrelated umbilical cord blood transplantation in hematological malignancies].

OBJECTIVE: To campare the effect and tolerance beween intensified myeloablative conditioning regime (IMCR) without antithymocyte globulin (ATG) and myeloablative conditioning regime (MCR) for single-unit unrelated umbilical cord blood transplantation (sUCBT) in hematological malignancies. METHODS: The clinical data of 190 patients with hematological malignancies undergoing sUCBT between April 2000 and December 2013 at Department of Hematology, Anhui Provincial Hospital were retrospectively analyzed, of whom 156 received IMCR without ATG (IMCR group), including 79 patient receiving total body irradiation (TBI)/cytosine arabinoside (Ara-C)/cyclophosphamide (CY) regime, 47 receiving fludarabine (Flu)/busulfan (Bu)/CY regime, and 30 receiving Ara-C/Bu/CY regime, and all of the 156 received a combination of cyclosporine A (CsA) and mycophelonate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD); the remaining 34 patients received MCR (MCR group), 30 patients receiving Bu/CY regime, and 4 receiving TBI/CY regime, all using CsA/MMF±ATG or methotrexate (MTX) for the prophylaxis of GVHD. The two groups were compared in disease status at the time of transplantation, characteristics of graft, transplantation effect, and transplantation-related complications. RESULTS: There were no statistically significant differences between the two groups in gender, disease type, human leukocyte antigen match, ABO blood type match, and disease status at the time of transplantation (all P>0.05). The median age and body weight at transplantation in the IMCR group were significantly higher than those in the MCR group (13 years vs 9 years, P=0.003; 44 kg vs 26 kg, P=0.000). The median doses of infused total nucleated cells (×10(7)/kg) and CD34(+) cells (×10(5)/kg) in the IMCR group were significantly lower than in the MCR group (3.87 vs 4.99, P=0.002; 2.00 vs 3.17, P=0.000). The cumulative incidence of myeloid engraftment on the 42th day and platelet engraftment on the 120th day in the IMCR group were remarkably higher than in the MCR group [96.33%(95%CI: 96.27%-96.39%)vs 82.30%(95%CI: 80.67%-83.93%), P=0.000; 86.44%(95%CI: 86.28%-86.60%)vs 51.17%(95%CI: 49.02%-53.32%), P=0.002]. There were no statistically significant differences in the incidences of grade Ⅱ to Ⅳ acute GVHD, grade Ⅲ to Ⅳ acute GVHD, and 2-year chronic GVHD(P=0.482, 0.928, 0.579). The incidence of pre-engraftment syndrome in the IMCR group was higher than in the MCR group(82.70% vs 47.06%, P=0.000). And 180-day transplantation-related mortality (TRM) in the IMCR group was lower than that in the MCR group [20.50%(95%CI: 20.28%-20.71%)vs 42.20% (95%CI: 41.32%-45.09%), P=0.004]. Up to October 2015, with a median follow-up of 44.2(22.7-188.9)months, the estimated 3-year overall survival and disease-free survival in the IMCR group were both significantly higher than those in the MCR group (62.90% vs 34.10%, P=0.000; 58.60% vs 34.10%, P=0.001). CONCLUSION: IMCR without ATG may improve the engraftment without increasing complications, reduce early transplantation-related mortality, and improve survival.

[Pathogens and clinical characteristics of bacterial infection in hematology department between 2010 and 2014].

OBJECTIVE: To analyze the characteristics of distribution and drug resistance of bacterial infection in several different parts of hematology department inpatients of Anhui Provincial Hospital from January 2010 to December 2014, including patients who had received hematopoietic stem cell transplantation (HSCT). METHODS: Anti-microbial susceptibility test was done by Kirby-Bauer method and automated systems and the data were analysed by WHONET 5.6 software. RESULTS: A total of 3 312 copies of inspection samples were analyzed, including 2 716 (82%) blood samples and other 596 specimens (18%). 634 bacterial strains were isolated from 3 312 samples (19.14%) including 488 samples (76.97%) from blood culture. 427 (67.35%) bacterial strains were gram-negative, and the other 207 (32.65%) were gram-positive. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were most common gram-negative bacterial and the resistant rates to imipenem were 0.8%, 11.8% and 3.3%, respectively. Detection rates of Extended-spectrum beta-lactamases in Escherichia coli and Klebsiella pneumoniae were 83.9% and 75.0%, respectively. At the same time, Coagulase negative Staphylococcus, Streptococcus and Enterococcus were most common kinds of gram-positive bacteria. Methicillin-resistant coagulase negative staphylococcus accounted for 65.9% antibiotic resistance. No vancomycin and/or linezolid and/or tigecycline resistant strains of Staphylococcus spp. and Enterococcus spp. were found in those patients. CONCLUSION: Patients with hematology diseases had a higher risk of bacterial infections, mainly caused by Gram-negative bacteria. There are different distributions of bacterial in different wards.

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission.

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤ 2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02) × 107/kg and that of CD34⁺ stem cells was 2.08 (range 0.99-8.65) × 105/kg. All patients were engrafted with neutrophils that exceeded 0.5 × 109/L on median day +17 (range 14-37 days) and had platelet counts of >20 × 109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients.

Primary graft failure (pGF) is a frequent complication following cord blood transplantation (CBT). For those patients who will not experience autologous recovery, salvage transplantation should be performed as early as possible. However, standardized treatment protocols for pGF, such as the optimal stem cell source, preparative regimen and the ideal time for salvage transplantation, have yet to be determined. Therefore, we analyzed 17 hematologic malignancy patients who received unmanipulated haploidentical peripheral blood (PB) and BM transplantation with reduced-intensity conditioning (RIC) as a salvage therapy for pGF after CBT. The median interval between the two transplantations was 38 days. The RIC regimen for salvage transplantation consisted of fludarabine, antithymocyte globulin, CY and low-dose TBI. The neutrophil and plt engraftments were achieved in 14 (82.4%) and 13 (76.4%) patients, respectively. The cumulative incidences of grades II-IV and grades III-IV aGVHD were 35.3% and 17.6%, respectively. The cumulative incidence of chronic GVHD was 29.4%. After a median follow-up of 43 months, 10 of 17 patients remained alive in CR. The cumulative incidence of TRM at 180 days was 29.4%. The probability of 3-year OS and leukemia-free survival was 57.5%. Our results show that unmanipulated haploidentical PB and BM transplantation under a RIC regimen is an effective treatment for pGF after CBT.

Similar survival, but better quality of life after myeloablative transplantation using unrelated cord blood vs matched sibling donors in adults with hematologic malignancies.

This study included data from 185 consecutively treated patients, 16 years of age or older, who underwent myeloablative transplantation using unrelated umbilical cord blood (UCB) (UCB transplantation (UCBT), n=70) or HLA-identical sibling donor peripheral blood stem cells alone or combined with bone marrow (BMT/PBSCT, n=115) from October 2001 to December 2012. All patients received myeloablative regimens, cyclosporin A plus mycophenolate mofetil as prophylaxis for GVHD, and similar supportive care. Although hematopoietic recovery was significantly delayed after UCBT, the rate of neutrophil engraftment was comparable. The median follow-up was 53 months (range, 15-136 months) for BMT/peripheral blood SCT (PBSCT) recipients and 35 months (range, 10-123 months) for UCBT recipients. There were no significant differences in the cumulative incidence of grades III to IV acute GVHD, relapse rate, or 3-year probabilities of disease-free survival between patients receiving UCBT and those receiving BMT/PBSCT. However, the cumulative incidence of chronic and extensive chronic GVHD was lower in UCBT recipients. The rates of long-term survivors returning to school or work and off immunosuppressive therapy were significantly higher after UCBT, which indicated that long-term survivors who underwent UCBT had a higher quality of life.

The effect on maternal temperature of delaying initiation of the epidural component of combined spinal-epidural analgesia for labor: a pilot study.

BACKGROUND: Labor epidural analgesia is associated with maternal hyperthermia. This pilot study compared the effects on maternal temperature during labor of different timing of initiation of the epidural component of combined spinal-epidural analgesia. METHODS: After induction of analgesia with intrathecal bupivacaine 2 mg and fentanyl 20 µg, healthy term nulliparas in spontaneous labor were randomized to receive immediate epidural analgesia (n=26) or delayed epidural analgesia after the return of pain (n=28), by patient-controlled epidural analgesia with 0.125% bupivacaine and fentanyl 1 µg/mL. Maternal tympanic temperature, visual analog scale pain score and dermatome block level were measured hourly during labor. RESULTS: The duration of labor for most parturients (83.3%) was <5 h. Mean maternal temperature gradually increased over time but did not significantly differ from either from baseline or between the two groups. There was no significant difference in the incidence of maternal fever (≥38°C) between the two groups. At 2 h post spinal analgesia the visual analog scale score was higher (P=0.03) and the dermatome block level was lower (P=0.005) in the delayed epidural analgesia group compared to the immediate epidural analgesia group. CONCLUSIONS: Delaying the epidural component of combined spinal-epidural analgesia did not significantly affect maternal temperature in the study population of whom 83.3% had a labor of <5 h. However, this study was underpowered to detect a difference in the incidence of fever and a larger prospective study is required.

Effects of intrathecal and i.v. small-dose sufentanil on the median effective dose of intrathecal bupivacaine for Caesarean section.

BACKGROUND: Spinal anaesthesia with bupivacaine combined with sufentanil has been widely used for Caesarean section. However, the main site of action (spinal vs central) of intrathecal (IT) sufentanil is controversial. The aim of this study was to examine the predominant mechanism of action of IT, small-dose sufentanil when added to bupivacaine for Caesarean section, by comparing the effects of IT and i.v. sufentanil 2.5 microg on the median effective dose (ED50) of bupivacaine. METHODS: Ninety parturients undergoing elective Caesarean section with a combined spinal-epidural technique were enrolled into this prospective, double-blind, up-down sequential allocation study. According to the up-down sequential allocation, parturients received varying doses of bupivacaine alone (C group) or co-administered with i.v. sufentanil 2.5 microg group (IVS group; n = 30) or IT sufentanil 2.5 microg group (ITS group; n = 30). The possible maternal or neonatal adverse effects were also recorded. RESULTS: The ED(50) of bupivacaine was 6.3 mg (95% CI 6.2-6.5) in the C group, 5.2 mg (95% CI 5.1-5.4) in the IVS group, and 3.0 mg (95% CI 2.9-3.1) in the ITS group. The ED50 in the ITS group was significantly lower as compared with the other two groups (P < 0.0005). With the exception of pruritus that exclusively occurred in the ITS group (P = 0.011, compared with the other two groups), no significant differences among groups were observed regarding the frequencies of the maternal or neonatal adverse effects. CONCLUSIONS: Compared with an equal dose of sufentanil i.v., intrathecally administered sufentanil 2.5 microg has a significant local anaesthetic-sparing effect via a predominantly spinal mechanism for Caesarean section.

Coaxing bone marrow stromal mesenchymal stem cells towards neuronal differentiation: progress and uncertainties.

Multipotent adult stem cells capable of developing into particular neuronal cell types have great potential for autologous cell replacement therapy for central nervous system neurodegenerative disorders and traumatic injury. Bone marrow-derived stromal mesenchymal stem cells (BMSCs) appear to be attractive starting materials. One question is whether BMSCs could be coaxed to differentiate in vitro along neuronal or glial lineages that would aid their functional integration post-transplantation, while reducing the risk of malignant transformation. Recent works suggest that BMSCs could indeed be differentiated in vitro to exhibit some cellular and physiological characteristics of neural cell lineages, but it is not likely to be achievable with simple chemical treatments. We discussed recent findings pertaining to efforts in neuronal differentiation of BMSCs in vitro, and results obtained when these were transplanted in vivo.

APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin-alpha connection.

Protein ubiquitination has critical roles in neuronal physiology and defects in protein ubiquitination have been implicated in neurodegenerative pathology. The anaphase-promoting complex/cyclosome (APC/C) is one of two key E3 ubiquitin ligase complexes that functions in regulating cell cycle transitions in proliferating cells by acting on cyclins and components of the mitotic/meiotic apparatus. Documentation of APC/C's action beyond cell division is sparse. In the past year, however, novel and surprising roles for APC/C in postmitotic neurons, particularly in the modulation of axonal growth and synaptic functions, have been revealed. APC/C and its activator Cdh-1 are found in good abundance in neurons, and these seem to function at different cellular locations, modulating apparently diverse processes such as axonal growth and synaptic function. Interestingly, there also appears to be a single link to these apparently divergent actions of APC/C in neurons--the multi-domain, multi-functional scaffolding protein Liprin-alpha which is an APC/C substrate.