The time-dependent effects of early-onset Epstein-Barr viremia on adult acute leukemia patients following allo-HSCT with ATG-containing MAC regimen.

Epstein-Barr virus (EBV) viremia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the impacts of early-onset EBV viremia in acute leukemia (AL) patients who underwent allo-HSCT with anti-thymocyte globulin (ATG)-containing myeloablative conditioning (MAC) regimen. Two hundred and ninety-six patients were included between January 2013 and December 2015. In 126 patients (42.6%) who developed early-onset EBV viremia, with a median time of 48 (range 18~99) days after allo-HSCT. The cumulative incidence of EBV viremia at 30 and 90 days after allo-HSCT were 4.1 and 39.9%, respectively. Prognostic analysis showed that the adjusted overall survival in early-EBVpos group was significantly lower than early-EBVneg group within the first 26.7 months after allo-HSCT [hazard ratio (HR), 1.63, P = 0.012], but significantly higher than those afterward (after 26.7 months: HR 0.11, P = 0.035); for the adjusted event-free survival, early-EBVpos group was significantly inferior in early-EBVpos group within the first 10.8 months after transplantation (HR: 1.55, P = 0.042), and this adverse effect was not detected any more after 10.8 months (HR: 0.58, P = 0.107). Compared with early-EBVneg group after adjusting by aGVHD and CMV viremia, HR for death from transplant-related mortality was 2.78-fold higher in patients with early-EBV viremia in piecewise constant Cox analysis (P = 0.006), and this adverse effect was not detected any more after the cut-point time (HR: 0.67, P = 0.361). No differences in terms of relapse and relapse mortality were observed between early-EBVpos and early-EBVneg group (P > 0.05). In conclusion, the impacts on transplant outcomes of early-EBV viremia were time-dependent, which may help to optimize management strategies for early-EBV viremia after allo-HSCT, especially in AL patients with ATG-containing MAC regimen.

Outcome of Allogeneic and Autologous Hematopoietic Cell Transplantation for High-Risk Peripheral T Cell Lymphomas: A Retrospective Analysis From a Chinese Center.

Peripheral T cell lymphomas (PTCLs) often carry poor outcomes with conventional chemotherapy, and hematopoietic cell transplantation (HCT) can benefit patients with PTCL. We conducted a retrospective review of 67 patients with PTCL who underwent autologous HCT (autoHCT, n = 43; median age, 40 years) or allogeneic HCT (alloHCT, n = 24; median age, 36.5 years) from 2004 to 2016. With a median follow-up of 27 months, 5-year progression-free survival (PFS) and overall survival (OS) of autoHCT patients were 49% and 57%, respectively. Among alloHCT recipients, the 5-year PFS and OS were 54% and 55%, respectively. When considering incidence of disease relapse or progression (CIR) and nonrelapse mortality (NRM), the 5-year CIR and 1-year NRM of alloHCT recipients were 38% and 18%, respectively, and 58% and 7% for autoHCT patients, respectively. There were no differences between autoHCT and alloHCT in 5-year PFS (P = .499), OS (P = .566), CIR (P = .555), and NRM (P = .202). When specifically examining recipients in primary refractory disease, 3-year PFS rates of autoHCT and alloHCT were 20% and 49% (P = .054); 3-year OS rates were 20% and 53% (P = .042), respectively. Based on these results, we favor proceeding to alloHCT in patients with PTCL in primary refractory disease.

[Efficacies of hematopoietic stem cell transplantation for severe aplastic anemia: a report of 43 patients].

OBJECTIVE: To evaluate the efficacies of hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA). METHODS: A total of 43 SAA patients (SAA-I, n = 29; SAA-II, n = 14) underwent HSCT from 2002 January to 2013 December. There were 22 males and 21 females with a median age of 31 (12-49) years. And 35 patients received HLA-matched sibling HSCT (Sib-HSCT) while another 8 had unrelated donor HSCT (UD-HSCT). The hematopoietic stem cells were collected from bone marrow (n = 10), peripheral blood (n = 23) and bone marrow & peripheral blood (n = 10). Conditioning regimens were mostly composed of Fludarabine, antihuman thymocyte gloBulin and cyclophosphamide. Cyclosporine and methotrexate (including mycophenolate mofetil for UD) were offered for preventing graft-versus-host disease (GVHD). The median counts of mononuclear cell and CD34(+) stem cell were 8.1 (2.4-13.5) ×10(8)/kg and 3.7 (2.3-14.7) ×10(6)/kg respectively. RESULTS: Hematopoiesis reconstitution was achieved in 42 patients. The median periods for neutrophils to 0.5×10(9)/L and platelets to 20×10(9)/L were +10 (+8-+25) days and +14 (+8-+80) days respectively. The median of survival time was not reached. Overall survival (OS) and failure-free survival (FFS) at 5 years had no differences between UD-HSCT and Sib-HSCT groups (OS: 87.6% vs 84.5%, P = 0.87; FFS: 86.2% vs 79.5%, P = 0.64). The same results also were seen between age ≤ 20 group and > 20 group (OS: 92.0% vs 82.5%, P = 0.39; FFS: 91.0% vs 77.3%, P = 0.38). The median follow-up time was 17.0 (0.4-140.0) months. And 8/43 patients died from thrombotic microangiopathy (TMA) (n = 1), TMA associated with capillary leak syndrome (n = 1), pulmonary infection (n = 3), acute GVHD of grade IV (n = 1) and unknown causes (n = 2). CONCLUSIONS: Sib-HSCT is preferred for SAA patients under 40 years. Searching of HLA-matched unrelated donor should be performed soon after diagnosis if HLA-matched sibling is unavailable.

Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis.

The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.

[The association of killer cell immunoglobulin like receptor gene polymorphism with cytomegalovirus infection after hematopoietic stem cell transplantation].

OBJECTIVE: To explore the influence of the killer cell immunoglobulin like receptor (KIR) gene polymorphism on cytomegalovirus (CMV) infection and pathogenesis after hematopoietic stem cell transplantation (HSCT). METHODS: The KIR genotype was determined by sequence-specific primer polymerase chain reaction (PCR-SSP) in 138 pairs of donors and recipients before HSCT during October, 2005 and May, 2011. Posttransplant monitoring for CMVpp65 antigen was performed by indirect immune histochemically assays since week 2 after transplantation. The differences between CMV positive group and negative group, inhibitive and active KIR of donors and recipients, and KIR haplotype frequency of donors and recipients were analyzed. RESULTS: There were no significant differences in frequency of KIR gene and haplotype AA, AB, BB between the donors and recipients. The frequencies of 2DS2 and 2DS4 * 003-007 of donors in CMV positive group were obviously lower than those in CMV negative group with significant differences (8% vs 16% , P = 0.0420; 3% vs 13%, P = 0.0050). There was no significant difference in KIR gene between CMV positive group and CMV negative group. The CMV infection rates of haplotype AA, BB, AB donors were 64.38%, 36.84% and 50.00%, while CMV infection rates of haplotype AA, BB, AB recipients were 53.73%, 46.15% and 51.72%, respectively. The CMV infection rate was higher in the patients received KIR haplotype AA donor than in those received KIR haplotype BB donor (36.84% vs 64.38%, P = 0.0299). 2DS4 x 003-007 and haplotype BB of donor were found associated with CMV infection in multifactor analysis. CONCLUSION: KIR genotypes of donors are associated with CMV infection after HSCT.

[Impact of induced therapy before allogeneic hematopoietic stem-cell transplantation for higher-risk myelodysplastic syndrome: experience of single centre].

OBJECTIVE: To explore the impact of prior-to-transplantation induction therapy (IT) on patient outcome after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) for higher-risk myelodysplastic syndromes (MDS). METHODS: A total of 49 consecutive patients underwent Allo-HSCT for MDS between November 2002 and December 2012. Twenty-six lower-risk MDS cases received supportive therapy (ST). And 17/23 cases of higher-risk MDS received IT prior to transplantation while another 6 only with ST. Their survival, relapse rate and incidence of transplantation-related mortality (TRM) were retrospectively analyzed according to International Prognostic Scoring System (IPSS) scores and marrow blast count. RESULTS: The 5-year cumulative overall survival (OS), disease-free survival (DFS), relapse rate and incidence of transplantation related mortality (TRM) were 59.9%, 59.2%, 10.5% and 31.8% during a median follow-up period of 24.4 (6.2-72.0) months. The OS and DFS of higher-risk group with IT, ST and lower-risk group were different (72.1% vs 16.7% vs 68.1%, P = 0.028; 72.1% vs 16.7% vs 67.9%, P = 0.030). And the OS and DFS of higher-risk group with IT were similar to those of lower-risk group (P = 0.526,0.504) . For the higher-risk group, the patients on IT had improved survival than those on ST in terms of OS and DFS (both P = 0.020). Moreover, the OS and DFS of remission group were higher than non-remission group in patients on IT (both 100% vs 46.7%, P = 0.049). The number of marrow blasts significantly decreased after IT (P = 0.010) without increased TRM (28.9% vs 33.6%, P = 0.612). CONCLUSION: Induction therapy prior to Allo-HSCT for MDS may reduce clone burden and improve the outcomes of higher-risk MDS without increased TRM.

[Lower risk myelodysplastic syndrome patients with transfusion dependent treated by dose-reduced decitabine].

OBJECTIVE: To evaluate the efficacy and safety of dose-reduced decitabine for the lower risk myelodysplastic syndrome (MDS) patients with transfusion dependent. METHODS: Twenty-five cases of lower risk (low or intermediate-1 risk in IPSS risk group) MDS patients with transfusion dependence from November 2009 to September 2012 were treated by dose-reduced decitabine (20 mg/m(2) intravenously once daily for 3 days). And their efficacy, side effects, quality-of-life and survival rate were evaluated. RESULTS: Among them, the responses included complete remission (CR, n = 3, 12%), transfusion independence (n = 4, 16%), hematologic improvement (HI, n = 8, 32%) and stable disease (SD, n = 2, 8%). And the overall response rate (ORR) was 68% (17/25) . Among 11 cases available for cytogenetic evaluation, 1 achieved partial cytogenetic remission (PRc). IV grade hematologic toxicity rate was 48% (12/25) and III-IV grade infection rate 20% (5/25). No severe hematologic toxicity was observed. After treatment, the Karnofsky performance score (KPS) increased from 47 ± 16 to 66 ± 22 (P = 0.001); more patients were reclassified as WPSS ≤ 1 (44%vs 16%, P = 0.031) or MDACC score ≤ 7 (64% vs 8%, P = 0.022). The median follow-up time was 467(14-881) d. The 100 and 600-day expected survive rates of low and intermediate -1 risk in IPSS risk group were 100% versus 95.2% and 100% versus 90.5%. CONCLUSIONS: Dose-reduced decitabine is well-tolerated and effective in transfusion dependent MDS patients in IPSS-lower risk. There is a low rate of severe hematologic toxicity and early mortality. It may prolong their survival time.

Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series.

BACKGROUND: Biphenotypic acute leukemia (BAL) is a rare type of acute leukemia that presents with a high degree of heterogeneity and is not well defined. METHODS: We identified 51 cases (3%) of BAL from 1,693 newly diagnosed acute leukemia patients according to the EGIL scoring system. The immunophenotyping, cytogenetics, treatment, and outcome of 39 BAL patients were retrospectively analyzed. RESULTS: There were 23 (59%) cases of the myeloid and B-lymphoid phenotype, 14 (36%) cases of the myeloid and T-lymphoid phenotype, and 1 case (3%) of the trilineage phenotype or B/T phenotype. Abnormal karyotypes were detected in 76% of the 37 validated patients and displayed a high degree of heterogeneity. Combined regimens for both acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), as well as ALL type regimens, appeared to achieve a better complete remission rate than AML type regimens (71 and 64 vs. 33%, respectively). BAL patients with complex karyotypes or a rearrangement of chromosome 11 had a significantly reduced survival rate in comparison to patients with normal, t(8; 21), or t(9; 22) karyotypes. The probability of overall survival and disease-free survival at 2 years was 26 and 18%, respectively. CONCLUSIONS: Our findings indicate that BAL shows a high incidence of abnormal karyotypes and a poor prognosis. Combined-type regimens or ALL-based protocols are effective for the treatment of BAL.

Cytomegalovirus glycoprotein B genotype in hematopoietic stem cell transplant patients from China.

Cytomegalovirus (CMV) can be classified into 4 subgroups based on genotype variation of the glycoprotein B (gB) encoded by UL55 gene. Little is known about the CMV gB genotype distribution and its clinical implication in patients who receive hematopoietic stem cell transplant (HSCT) in China. In this study, which comprises 101 HSCT patients with CMV infection, we have found that 36 patients (35.64%) were infected with CMV genotype gB1, 3 patients (2.97%) with gB2, 39 patients (38.61%) with gB3, 1 patient (0.99%) with gB4, and 17 patients (16.83%) were infected with mixed CMV genotypes. We also found that CMV gB3 was associated with a high risk of CMV pneumonitis; nevertheless, there were no significant differences among patients with gB genotypes with respect to the other CMV diseases; no significant differences between patients with gB genotypes with respect to type II-IV acute graft-verses-host disease (aGVHD) and chronic GVHD (cGVHD) was found either. Interestingly, 5 patients (4.95%) were infected with a CMV variant that lacked a signature RsaI digestion site determined by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), subsequent cloning and sequencing identified this CMV RsaI minus variant to be novel, herein designated as gB5. Overall, these findings suggest that CMV gB1 and gB3 are prevalent among HSCT recipients with CMV infections, and gB3 CMV infection is a risky indicator for CMV pneumonitis; furthermore, a novel CMV variant in a subset of Chinese HSCT recipients is identified and designated as gB5.

Allogeneic Donor-Derived Anti-CD19 CAR T Cell Is a Promising Therapy for Relapsed/Refractory B-ALL After Allogeneic Hematopoietic Stem-Cell Transplantation.

INTRODUCTION: Currently, effective and safe salvage therapies are limited among patients with relapsed acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Anti-CD19 chimeric antigen receptor T (CAR T) cell is a promising treatment. PATIENTS AND METHODS: We studied 11 patients with B-cell acute lymphoblastic leukemia that relapsed after allo-HSCT between September 2017 and October 2019. Patients were treated with a dose of single-infusion donor-derived anti-CD19 CAR T cells. RESULTS: Eight patients (72.7%) experienced morphologic remissions. Seven (63.6%) experienced minimal residual disease-negative remission. The ongoing complete remission (CR) duration of 2 patients reached 22 months. The median overall survival was 9 months (range, 2-22 months). Only one patient with grade 1 acute graft-versus-host disease was observed. Two patients (18.2%) developed grade 3/4 cytokine release syndrome. CONCLUSION: This prospective study showed allogeneic donor-derived anti-CD19 CAR T-cell therapy is an effective and safe salvage regimen for patients with relapsed/refractory B-cell acute lymphoblastic leukemia after allo-HSCT. Further randomized and multicenter investigations are needed to evaluate their potential role in relapsed acute lymphoblastic leukemia therapies after allo-HSCT.

Anti-CD19 chimeric antigen receptor T-cells induce durable remission in relapsed Philadelphia chromosome-positive ALL with T315I mutation.

Effective treatments for relapsed Ph+ALL with T315I mutation are few; CD19 CAR T-cell therapy are a potential therapy for this condition. We reported 7 patients with relapsed Ph+ALL with T315I mutation, who were treated pre- or post-allo-HSCT with CD19-specific CAR T-cells. Of the 7 cases, 6 were in CR or CRp within 1 month after the first infusion of CAR T-cells. MRD revealed a rapid decline in 6 patients. BCR/ABL fusion transcripts were negative in 4/5 cases (not performed in 2). Three patients maintained remission without evidence of MRD by QPCR until the final follow-up, of which 2 received anti-CD19 CAR T-cells and ponatinib at the same time. Our study confirmed the efficacy of anti-CD19 CAR T-cell therapy in treatment of relapsed Ph+ALL with T315I mutation pre- or post-allo-HSCT and the concurrent applicability of this therapy with ponatinib.

Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation: multifactorial impact on transplant outcomes.

Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic cell transplantation (allo-HCT) is one of the major concerns that may lead to fatal EBV diseases. However, updated data are needed because of the remarkable evolution of the HCT protocol and donor selection. We conducted a retrospective study that enrolled 890 allo-HCT recipients. Independent risk factors for EBV reactivation were use of antithymocyte globulin, haploidentical donor, and the presence of chronic graft-versus-host disease. The cumulative incidence of EBV reactivation was 2.9%, 11.7%, 27.3%, and 41.9% for patients with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). Posttransplant lymphoproliferative disorders (PTLDs) occurred in seven patients. EBV reactivation was associated with inferior survival in recipients who survived more than 2 years post-HCT (P < 0.001) but might time-dependently benefit those patients with malignancies by decreasing relapse incidence (P = 0.046). A decreased relapse incidence was observed 1 year after HCT for recipients at first or second remission (P = 0.042) and in the first year post-HCT for recipients with advanced diseases (P = 0.032). We concluded that with current management, PTLDs were efficiently controlled, but EBV reactivation still had a multifactorial impact on transplant outcomes. Multicenter prospective studies are warranted to validate these findings.

Partially matched related hematopoietic stem cell transplantation without ex vivo T cell depletion compared with matched unrelated transplantation in adult patients with hematologic malignancies.

The optimal alternative donor for adult hematopoietic stem cell transplantation (HSCT) candidates who lack an ideal histocompatible sibling remains controversial. We studied the clinical outcomes of 88 adult patients with hematologic malignancies who received a partially matched related donor (PMRD) transplant (n=36) or a matched unrelated donor (MUD) transplant (n=52) with a uniform myeloablative protocol without ex vivo T cell depletion. Age and other characteristics were comparable in the 2 groups, except that the PMRD group had a higher proportion of bone marrow (BM) grafts. Primary engraftment was achieved in nearly 98% of the whole cohort. The incidences of acute grade III-IV and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 15% and 16% in the PMRD group and 16% and 14% in the MUD group. Although treatment-related mortality (TRM) was 42% in the PMRD group and 31% in the MUD group (P=.29), the relapse rate was<11% for the whole cohort. With a median follow-up of 30 months, no statistically significant difference was observed in 3-year overall survival (OS) and event-free survival (EFS) between the PMRD group (45% and 38%) and the MUD group (54% and 50%). These data demonstrate that HSCT performed with PMRD can be an alternative option for treating adult patients with hematologic malignancies.

Outcomes of CAG regimen for refractory biphenotypic acute leukemia patients.

OBJECTIVE: To evaluated the efficiency of low-dose cytosine arabinoside plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor (CAG) regimen for refractory biphenotypic acute leukemia (BAL). METHODS: We treated 5 refractory BAL patients by CAG regimen (10 mg x m(-2) cytosine arabinoside subcutaneously administrated every 12 hours, day 1-14; 5-7 mg x m(-2) aclarubicin intravenously administrated daily, day 1-8; and concurrently used 200 microg x m(-2) x d(-1) granulocyte colony-stimulating factor subcutaneously) from November 2002 to April 2007. The efficacy of the regimen was evaluated by response rate, and the side effects were also measured. RESULTS: The complete remission rate was 80%, median duration of absolute neutrophil count < 5.0 x 10(8)/L and platelet count < 2.0 x 10(10)/L was day 13 and day 1, respectively; and the infection rate was low (III-IV infection rate, 20.00%). CONCLUSION: CAG regimen as remission induction chemotherapy for BAL patients is effective with a high remission rate and low toxicity.

Whole-body diffusion-weighted MRI for evaluation of response in multiple myeloma patients following bortezomib-based therapy: A large single-center cohort study.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted imaging (WB-DWI) MRI for evaluation of response in patients with multiple myeloma (MM) following bortezomib-based therapy and to explore the direction of apparent diffusion coefficient (ADC) changes upon treatment. METHOD: Seventy-two MM patients who underwent WB-DWI MRI before and after bortezomib-based chemotherapy (21 weeks) were evaluated retrospectively. The estimated tumor volume (eTV) and ADCmean values before and after chemotherapy were calculated and compared between deep and non-deep responders. Predictive value of baseline ADCmean was calculated to predict the trend of ADCmean change following treatment. RESULTS: Fifty-five patients were classified as deep responders, and 17 cases were assigned as non-deep responders. For 327 focal lesions (FLs), the ADCmean value was significantly increased from baseline to post-treatment. However, the ADCmean value was significantly decreased following treatment in 846 representative diffuse lesions. Diffuse lesions showed a significantly decreased ADCmean value in deep responders, whereas no significant variation in ADCmean value in FLs was found between deep and non-deep responders. Baseline ADCmean at a specific value (0.808 × 10-3 mm2/s) yielded a maximum specificity (68.05%) and sensitivity (54.09%) in predicting increase of post-treatment ADCmean. CONCLUSIONS: The ADCmean value was significantly decreased in MM patients with diffuse pattern, while it was significantly increased in those with focal pattern following bortezomib-based treatment. WB-DWI MRI could be used to discriminate deep response to induction treatment in MM patients with diffuse infiltration pattern. Baseline ADCmean value might have a potential to predict the trend of ADCmean change following treatment.

Allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in second chronic phase attained by imatinib after onset of blast crisis.

The prognosis for patients with chronic myeloid leukemia (CML) in blast crisis (BC) remains dismal even with the availability of the BCR-ABL tyrosine kinase inhibitor imatinib, since it only offers short-term benefit in most cases. Allogeneic hematopoietic stem cell transplantation (HSCT) seems to be a viable option for BC-CML patients who attained remission. We treated ten patients with ablative allogeneic HSCT, who achieved second chronic phase (CP) by the use of imatinib after onset of BC. Median patient age was 32 years (range 17-46). Among them, four patients received HSCT from human leukocyte antigen mismatched haplo-identical family donors. After a median follow-up of 24 months (range 8-42), six out of the ten patients were alive in durable complete cytogenetic remission, one patient died in relapse 4 months after transplantation, the others died of severe acute graft-versus-host disease and associated infections. No unusual organ toxicities and engraftment difficulties were observed. Extensive chronic GVHD developed in three of six patients who could be evaluated. Patients transplanted with haplo-identical donors had a high treatment-related modality. Allogeneic HSCT may represent a feasible treatment for patients with CML in second CP attained by imatinib after onset of BC especially when a suitable donor is available.

B-Lymphoid and myeloid lineages biphenotypic acute leukemia with t(8;21)(q22;q22).

By analyzing the characteristics of morphology, immune phenotype, chromosome karyotype and clinical manifestations of six cases of B-lymphoid and myeloid lineages biphenotypic acute leukemia (BAL) with t(8;21)(q22;q22), a new subgroup of BAL was reported. Bone marrow eosinophilia (more than 5%) and pseudo-Chediak abnormalities were not found. Auer rods were also not identified in four of six cases. Immunophenotype revealed B-lymphoid and myeloid lineages positive, together with frequent and high expression of CD34 and CD33, and weak expression of HLA-DR. In addition to t(8;21) chromosomal translocation, deletion of Y chromosome and complex chromosome abnormalities were also found. Chemotherapy for myeloid and lymphoid leukemia simultaneously produced good response in the patients. BAL with t(8; 21)(q22; q22) might be a new subgroup of BAL, and it was suggested that the leukemia clone with t(8;21)(q22;q22) might have originated from an early phase of hematopoiesis, and AML1/ETO fusion gene might be related to differentiation of B lymphocyte.

Consolidation therapy with decitabine and intermediate-dose cytarabine followed by HLA-mismatched peripheral blood stem cells infusion for older patients with acute myeloid leukemia in first remission.

This retrospective study tested the feasibility of decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) infusion as consolidation treatment for older patients with acute myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy (chemo group). The two regimens were well tolerated. The median recovery times for neutrophils and platelets were shorter in D-GPBSCs group than in chemo group (p<.05). No graft-versus-host disease (GVHD) was observed in D-GPBSCs group. The 2-year leukemia-free survival (LFS) and overall survival (OS) were better in D-GPBSCs group (51.6 and 55.4%) than in chemo group (27.1 and 34.2%) (p = .047 and p = .056). These data suggest that DAC and ID-AraC followed by GPBSCs as a consolidation regimen may be a safe and promising option for older patients with AML.

High Tim-3 expression on AML blasts could enhance chemotherapy sensitivity.

T-cell immunoglobulin and mucin domain-containing molecule3 (Tim-3) represents a novel mechanism of T-cell dysfunction and exhaustion. Tim-3 has also been identified in various solid tumors. However, the role of Tim-3 expression on blast cells in acute myeloid leukemia (AML) is not well understood. In this study, we aimed to explore the role of Tim-3 in patients with de novo AML, and the correlation between Tim-3 and clinicopathological prognosis. The study cohort consisted of 76 patients with de novo non-M3 AML. These patients' bone marrow samples were collected and then bone marrow mononuclear cells (BMCs) were isolated for flow cytometry to detect Tim-3 expression on blasts. According to FAB type, 76 diagnosed AML patients included in this study were: M0 (n=2), M1 (n=16), M2 (n=20), M4 (n=20), M5 (n=16), and M6 (n=2). A positive expression (>20%) of Tim-3 was found in 87% (66/76) of patients with AML. The average percentage of Tim-3(+) blasts in these AML patients was 58.26 ± 29.23%. Moreover, the frequency of Tim-3 high expression was higher in M4 patients than that in other AML patients according to FAB type (P=0.004). Tim-3 high expression was also closely associated with inv(16) (P=0.01) and C/EBPA mutation (P=0.03). The mutations of the following six genes, i.e., FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, were independent of the Tim-3 expression. Additionally, it is more likely to find higher levels of Tim-3 in the low-risk group than in the intermediate- and high-risk groups (P=0.02). The expression of Tim-3 was positively correlated with CD13 (r=0.36, P=0.001), CD34 (r=0.41, P=0.000), and CD7 (r=0.27, P=0.02) in AML patients. AML patients with high Tim-3 expression achieved significantly high complete remission (CR) rate (P=0.01), while their Tim-3 expression significantly decreased after CR (P=0.01). Blockade of Tim-3 expression on AML blasts significantly reduced the Idarubicin (IDA)-mediated suppression of cell growth and reduction of cell apoptosis in vitro. Collectively, our study suggests that high Tim-3 expression on AML blasts could enhances chemotherapy sensitivity.

The complete chloroplast genome sequence of Sapindus mukorossi.

The complete chloroplast genome sequence of Sapindus mukorossi, a critical Chinese medicine, was reported here. The total length of the chloroplast genome is 160,481 bp long with 37.7% overall GC content. A pair of IRs (inverted repeats) of 27,979 bp were separated by SSC (18,873 bp) and LSC (85,650 bp). It contains 78 protein-coding genes, 30 tRNA genes and four rRNA genes. Sixteen genes contain one or two introns.