Donglin Yang

Risk factors and prognosis of invasive fungal infections in allogeneic stem cell transplantation recipients: a single-institution experience

P. Zhang, E.‐L. Jiang, D.‐L. Yang, Z.‐S. Yan, Y. Huang, J.‐L. Wei, M. Wang, Q.‐L. Ma, Q.‐G. Liu, D.‐H. Zou, Y. He, L.‐G. Qiu, S.‐Z. Feng, M.‐Z. Han. Risk factors and prognosis of invasive fungal infections in allogeneic stem cell transplantation recipients: a single‐institution experience. Transpl Infect Dis 2010: 12: 316–321. All rights reserved

Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission

Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRDneg after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario.

Treatment of hematologic malignancies with alternate hemibody irradiation combined with high-dose chemotherapy: A single-center experience

The objective of this study was to evaluate the clinical outcome of the treatment of hematologic malignancies with alternate hemibody irradiation (AHBI) combined with high-dose chemotherapy. Seventeen patients with hematologic malignancies were treated with AHBI combined with high-dose chemotherapy. Following high-dose chemotherapy, upper hemibody irradiation (UHBI) and lower hemibody irradiation (LHBI) were given sequentially in a dose of 6 to 9 Gy. UHBI was given 14 days (range, 12-22 days) after high-dose chemotherapy, and LHBI was performed 23 days (range, 7-34 days) after UHBI. Meanwhile, we treated a control group of 14 patients with acute lymphoblastic leukemia (ALL) with autologous hematopoietic stem cell transplantation (AHSCT). Hematopoietic reconstitution was observed in all of the patients. The median follow-up period was 927 days (range, 428-1446 days). The 3-year probabilities of disease-free survival (DFS) were 52.38% ± 13.47% for the patients in complete remission who underwent AHBI. No patient died of AHBI-related toxicity. The 3-year DFS rates for the 2 groups of patients with ALL were not significantly different (47.73% ± 17.55% in the AHBI group and 53.88% ± 14.08% in the AHSCT group; P >.05). AHBI combined with high-dose chemotherapy is a feasible approach for patients with hematologic malignancies and has the advantages of a desirable effectiveness, low costs, simple operation, and acceptable side effects.

Pre-transplantation thymic function is associated with the risk of acute graft versus host disease and cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

ABSTRACT Objectives: To analyze the kinetics of T-cell subsets and thymic function reconstitution after allogeneic hematopoietic stem cell transplantation (AHSCT); to determine whether sjTREC (signal joint TCR rearrangement excision circle) and CD31-positive recent thymic emigrant (CD31 + RTE) are correlated with acute graft versus host disease (aGVHD) or CMV (cytomegalovirus) viremia after AHSCT. Methods: Forty-nine patients who underwent AHSCT in our institution were prospectively enrolled. Periphery blood samples were collected before conditioning and at 1, 2, 3 months after AHSCT. T-cell subsets were analyzed with flow cytometry. Genomic DNA was purified from peripheral blood mononuclear cells (PBMCs), and sjTREC was quantified by real-time PCR. Impact of sjTREC and CD31 + RTE on aGVHD and CMV viremia was evaluated by univariate and multivariate Cox regression analyses. Results: The analyzed T-cell subsets and sjTREC of patients before AHSCT were all significantly lower than those of healthy donors (p < 0.05). sjTREC and CD31 + RTE were remarkably decreased in 3 months after AHSCT (p < 0.05). Patients with lower pre-transplantation sjTREC and CD31 + RTE level had higher incidence of CMV viremia after AHSCT (p < 0.05). sjTREC/106 PBMCs was negatively correlated with aGVHD (p = 0.024). Conclusion: Thymic function was impaired before transplantation, and was consistently decreased in 3 months after AHSCT. Patients who had lower pre-transplantation sjTREC level were at high risk of aGVHD and CMV viremia after AHSCT, low pre-transplantation CD31 + RTE was correlated with CMV viremia after AHSCT.

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia

ABSTRACT Objectives: Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients. Material and methods: We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories. Results: Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044). Discussion and conclusions: Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.

BCR-ABL enhances the prolyl isomerase activity of Pin 1 by interacting with DAPK1 in ph+ALL

Philadelphia chromosome (Ph)/BCR‐ABL‐positive (ph+) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR‐ABL. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph+ ALL. We further demonstrated that BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin 1 at Ser 71 and interacting with DAPK1. The inhibition of BCR‐ABL activity by imatinib in human ph+ ALL cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified BCR‐ABL‐Pin 1 axis in ph+ ALL progression. Thus, the combined suppression of Pin 1 and BCR‐ABL proteins may be exploited as an additional target therapy for ph+ ALL.

Effect of Antithymocyte Globulin Source on Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Severe Aplastic Anemia

We wanted to evaluate efficacy of porcine antithymocyte globulin (ATG) in HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation (MSD-HSCT) for patients with severe aplastic anemia (SAA). The clinical data of 113 SAA patients who received MSD-HSCT from January 2005 to November 2016 were analyzed retrospectively. Of these, 58 patients received rabbit ATG as a part of conditioning regimen (R-ATG group), whereas the other 55 patients received porcine ATG (P-ATG group). Patient baseline characteristics and donor conditions of the 2 groups were similar, except patients were older and more received peripheral blood stem cell transplantation in the P-ATG group. All patients engrafted in 2 groups. There were significant differences in the incidence of acute (20.7% ± 5.3% versus 43.4% ± 7.0%, P = .015) and chronic graft-versus- host disease (GVHD; 20.1% ± 5.8% versus 46.0% ± 7.9%, P = .003) between the R-ATG and P-ATG groups. However, there were no significant differences in terms of 3-year overall survival (93.1% ± 3.3% versus 84.4% ± 5.7%, P = .235), grades III to IV acute GVHD (3.4% ± 2.4% versus 12.3% ± 4.7%, P = .098), moderate to severe chronic GVHD (12.6% ± 4.9% versus 11.5% ± 4.9%, P = .905), or graft rejection (7.4% ± 3.6% versus 5.5% ± 3.1%, P = .852). There was also no significant difference with regard to the incidence of severe bacterial infection (P = .075), invasive fungal disease (P = .701), or cytomeglovirus viremia (P = .770). P-ATG showed satisfactory efficacy and safety compared with R-ATG in the setting of MSD-HSCT for SAA patients. P-ATG could be a potential alternative preparation for R-ATG, further offering the advantage of lower costs.

Efficacy and safety of posaconazole in hematopoietic stem cell transplantation patients with invasive fungal disease

AIM Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. This study reports real-world efficacy and safety of posaconazole (POS) in HSCT recipients with IFD. PATIENTS & METHODS We performed a retrospective study to investigate the efficacy and safety of POS oral suspension in 45 HSCT patients with IFD from December 2013 to December 2016. RESULTS The success rate at 12 weeks after POS treatment was 57.8%. Multivariate logistic regression analysis showed that persistent neutropenia, severe graft-versus-host disease, high-dose steroid and cytomegalovirus infection were independently associated with inferior responses to POS. POS caused some adverse effects of mild or moderate severity that were of short duration. CONCLUSION This study provides encouraging data regarding the efficacy and safety of POS in HSCT recipients. Neutropenia, graft-versus-host disease, steroid use and cytomegalovirus infection are possibly associated with inferior responses to POS therapy.