[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.

[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.

Unrelated cord blood transplantation for newly diagnosed patients with severe acquired aplastic anemia using a reduced-intensity conditioning: high graft rejection, but good survival.

We report a single-center experience in treating 18 consecutive patients with severe aplastic anemia (SAA) who received unrelated cord blood transplantation (CBT). The median age was 17 years (range 5-61 years). Sixteen cases received a reduced-intensity regimen composed of CY (total dose 1200 mg/m(2)), rabbit antithymocyte globulin (ATG, total dose 30 mg/kg) and fludarabine (FLU, total dose 120 mg/m(2)). CYA and mycophenolate mofetil were used as GVHD prophylaxis. Two patients were not evaluable for engraftment because of early death on day +21 and +22. Only one of the sixteen cases achieved engraftment, but experienced secondary graft failure 3 months post transplantation. Fifteen patients experienced primary graft rejection, but all of them acquired autologous recovery. The 3-month and 6-month cumulative incidence of response was 56% and 81%, respectively. So far, 16 patients have survived for 330-1913 days (median, 750 days) after transplantation. The probability of OS at 2 years was 88.9%. Our data indicate that CBT for newly diagnosed SAA using no irradiation but FLU and ATG-based conditioning still seems to inevitably lead to the high risk of rejection, but may facilitate autologous recovery and improve survival with low risk of transplant-related mortality.