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.

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.

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.

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.

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.

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.

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.

Comparison of outcomes in mixed phenotype acute leukemia patients treated with chemotherapy and stem cell transplantation versus chemotherapy alone.

The optimal treatment approach for mixed phenotype acute leukemia (MPAL) remains unknown, and prognostic factors for treatment outcomes need to be identified. In this study, 66 patients diagnosed with MPAL according to criteria published by the WHO in 2008 were retrospectively assessed to evaluate the effectiveness of treatment and identify predictive variables. Five patients died of severe infection after the first induction chemotherapy, 29 received alloHSCT after induction (HSCT group), and 32 received only chemotherapy (chemotherapy group). The 3-year OS and DFS estimates for the entire cohort were 45% and 38%, respectively, and the 3-year OS differed significantly between the HSCT and chemotherapy-only groups (77% versus 16%). Using multivariate analyses, we identified disease burden as a prognostic factor for transplantation outcome, with the 3-year OS being 80% among patients who achieved remission and only 45% among patients in cases of nonremission. Our results indicate that alloHSCT after chemotherapy offers a survival advantage compared with chemotherapy only, and patients in remission before transplantation may experience a better outcome.

Haploidentical hematopoietic stem cell transplant in paroxysmal nocturnal hemoglobinuria.

Eighteen patients with paroxysmal nocturnal hemoglobinuria (PNH) receiving allogeneic hematopoietic stem cell transplant (allo-HSCT), either from HLA-haploidentical donors (HRD; n = 10) or HLA-matched donors (n = 5 from siblings and n = 3 from unrelated donors), were retrospectively evaluated. One showed primary graft failure following unrelated-donor HSCT. He was given a second HRD-HSCT, but died from cytomegalovirus pneumonia after achieving hematopoietic recovery. The other 17 patients achieved sustained engraftment and full-donor chimerism. Four in the HRD-HSCT group experienced grade II/III acute graft-versus-host disease (aGVHD), and five in the HLA-matched HSCT group developed grade II aGVHD. Among all 18 patients, 10 developed chronic GVHD (cGVHD), only one patient receiving HRD-HSCT developed extensive cGVHD. Nine in the HRD-HSCT group and all those in the HLA-matched HSCT group were alive and transfusion-independent at last follow-up. Our findings suggest that allo-HSCT is a promising treatment for PNH, and HRD-HSCT is a viable option for patients with PNH who lack HLA-matched donors.

[The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen].

OBJECTIVE: To observe the clinical safety and efficacy of decitabine in patients of acute myeloid leukemia and myelodysplastic syndromes (MDS/AML). METHODS: Totally 79 patients with MDS/AML were divided into three groups: (1)Treated with decitabine alone (20 mg/m² for 5 days). (2) Combination of decitabine with half dose CAG chemotherapy (Acla 20 mg qod×3 d, Ara-C 10 mg/m² q12 h×7 d, G-CSF 300 µg/d, the dose of G-CSF adjust to the amount of blood routine). (3)Combination of decitabine with CAG chemotherapy (Acla 20 mg qod×4 d, Ara-C 10 mg/m² q12 h×14 d, G-CSF 300 µg/d, the dose of G-CSF adjust to the amount of blood routine). We observed complete remission (CR) rate, overall response rate (ORR) and overall survival (OS) of the three groups; meanwhile, we analyzed the factors relevant to decitabine efficacy and the prognosis. RESULTS: ORR in the three groups were 53.3%, 56.5% and 69.2% respectively, with no statistically significant differences (P>0.05). Due to the last follow-up at 2014.04.01, 20 patients still survived, 45 died, 14 were lost to follow-up. The 5-year cumulative survival rate of 79 patients was 25.3%, the 2-year survival were of the three groups were 34.8%, 24.8 and 29.2% respectively with no statistically significant differences (P>0.05). Adverse events of infection and bleeding were mainly caused by decitabine. Grade 3 to 4 hematological toxicities were observed in 72 cases with the average time for the lack of granulocytes as 14.8 days. 59 patients experienced infectious events, including grade 3 or 4 infections in 14 cases, grade 1 or 2 infections in 45 cases. There were no statistically significant differences (P>0.05) among the three groups in terms of infection rates, bleeding rates, duration of neutrophenia, mean MAP transfusion and mean platelet transfusion. 79 patients were safely through bone marrow suppression by anti-infective and supportive treatment without treatment-related deaths. CONCLUSION: Treating MDS/AML with decitabine alone, in combination with half or one course CAG regimen produced high efficacy. ORR of the combination of decitabine with one course CAG regimen was relatively higher. Three groups of patients were all well tolerated.

[Effect of decitabine on immune regulation in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Based on the representative articles in recent years, the different mechanisms of decitabine on immune regulation in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) are summarized. Decitabine improves the expression of WT1 gene to stimulate specific cytotoxic T cells which can enhance graft versus leukemia effect (GVL) and improve the expression of FOXP3 gene to stimulate regulatory T cells so as to inhibit the acute graft versus host disease (GVHD). Through the above-mentimed mechanisms, decitabine can improve both therapeutic effect and quality of life in the patients with AML after allogeneic HSCT.

[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.

[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.

Comparable outcomes of partially matched related and matched related allogeneic hematopoietic cell transplantation following reduced-intensity conditioning in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia.

Reports from multiple centers have shown that reduced-intensity allogeneic hematopoietic cell transplantation (RIC-HCT) is able to benefit some adult patients suffering from Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). However, the relationship between donor cell source and outcome of RIC-HCT in (Ph-)ALL patients has not been elucidated. In this study, we present the outcome of 57 (Ph-)ALL patients treated with reduced-intensity conditioning (RIC) followed by HCT from HLA-matched related (MRD, n = 34) or HLA partially matched related (PMRD, n = 23) donors from a multicenter cohort. Neutrophil recovery at day 100 occurred in 91.3 % of the PMRD group and 97.1 % of the MRD group (P = 0.84). One hundred days after treatment, the cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 30.4 % (95 % confidence interval [CI], 13.0-53.0 %) in patients who received PMRD grafts, and 27.3 % (95 % CI, 15.0-48.0 %) for those who received MRD grafts (P = 0.76). The cumulative risk of developing chronic GVHD was 59.4 % (95 % CI, 31.0-72.0 %) in the MRD group and 23.4 % (95 % CI, 4.0-43.0 %) in the PMRD group (P = 0.03). The cumulative incidence of relapse in patients who received PMRD grafts was 18.8 % (95 % CI, 3.0-34.0 %), while for those who received MRD grafts it was 37.2 % (95 % CI, 15.0-48.0 %) (P = 0.32). Overall treatment-related mortality was 41.6 % (95 % CI, 20.0-62.0 %) in the PMRD group and 19.9 % (95 % CI, 7.0-35.0 %) in the MRD group (P = 0.08). Relapse was the most common cause of mortality in the MRD group, while infection contributed to the majority of deaths in the PMRD group. The 3-year probability of disease-free survival did not differ significantly between the two groups (55.5 % for the PMRD group vs. 48.4 % for the MRD group; P = 0.81). These data strongly suggest that RIC-HCT performed with PMRD may represent an alternative treatment option for adult patients with (Ph-)ALL.

[Efficacy analysis of unrelated donor hematopoietic stem cell transplantation for treatment of high risk acute myeloid leukemia].

This study was purposed to investigate the therapeutic efficacy of unrelated donor hematopoietic stem cell transplantation (URD-HSCT) for patients with high risk and refractory acute myeloid leukemia (AML). Twenty-two patients with high-risk and refractory AML receive URD-HSCT were enrolled in this study. All the patients received myeloablative preconditioning regimen consisting of busulfan/cyclophosphamide (for 20 cases) or total body irradiation/cyclophosphamide (for 2 cases) before URD-HSCT. The cyclosporin A (CsA)/MTX/MMF/ATG were used to prevent the acute graft versus host disease (aGVHD). The results showed that 21 out of 22 patients acquired engraftment with implantation rate 95.5%. The median time of ANC ≥ 0.5×10(9)/L was 12 (10-19) days, and that of Plt ≥ 20×10(9)/L was 14 (5 - 22) days. The median follow-up time post transplantation was 18 (3 to 135.5) months. The 2-year overall survival (OS) and leukemia-free survival (LFS) were (53.9 ± 12.2) % and (49.1 ± 10.7)% respectively. Eight cases developed aGVHD. The cumulative incidence of aGVHD was (39.1 ± 10.6) %. Six patients developed I-II grade of aGVHD and two patients developed III-IV grade of aGVHD. The chronic graft versus host disease (cGVHD) was occurred in 6 patients (4 patients limited, 2 patients extensive) of the 19 evaluable patients. The cumulative incidence was (28.8 ± 9.6)%. Seven cases relapsed, and the cumulative response rate of 2 years was (35.8 ± 11) %. One of 9 patients died from sepsis before hematopoietic reconstruction, one died from lung infection, Six died from relapse and one relapsed patient died from IV grade of aGVHD post chemotherapy and donor lymphocyte infusion (DLI). The univariate analysis revealed that relapse was the major factor for the OS, and the sex, age, preconditioning regimen, aGVHD and infection didn't significantly influence the efficacy of URD-HSCT. The survival of patients with cGVHD was superior to those who didn't have cGVHD (83.3% vs 37%, P = 0.152). It is concluded that URD-HSCT is a safe and effective therapy for high-risk AML patients without related donor. Notably, patients with cGVHD had a better survival. Relapse is an unfavourable factor for the efficacy of URD-HSCT and adoptive immunotherapy such as DLI can prevent it and improve the prognosis to achieve the long-time survival.

[The correlation of cytomegalovirus gB genotype with viral DNA load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation].

OBJECTIVE: To explore the effect of CMV gB genotypes on viral load and treatment time in patients with CMV infection after hematopoietic stem cell transplantation (HSCT). METHODS: Viral load was detected by real-time (RT) quantitative polymerase chain reaction (PCR) (Q-PCR), CMV gB genotypes by PCR restriction fragment length polymorphism (RFLP) (PCR-RFLP) in 115 patients with CMV infection (CMV-DNA positive) after HSCT during July 2004 and May 2010. RESULTS: (1) The distribution of CMV gB genotypes in HSCT recipients were as following: gB1, 42/115 (36.52%); gB2, 3/115 (2.61%); gB3, 43/115 (37.39%); gB4, 2/115 (1.74%). 20 patients (17.39%) had a combination of 2 different CMV genotypes and 5 patients (4.35%) had a CMV variant that lacked an RsaI digestion site, herein named gB5. (2) The median viral load were 2.7×10(3)(1.81×10(3) ∼ 6.03×10(4)) in gB1, 4.0×10(3) (1.32×10(3) ∼ 6.39×10(4)) in gB3 and 1.2×10(4)(2.28×10(3) ∼ 6.50×10(5)) in mixed gB. There was no statistical difference in viral load between gB1 and gB3 (P > 0.050). There was significantly statistical difference in viral load between single-gB (gB1 or gB3) and mixed-gB (P < 0.05). (3) The median treatment time was 17 days in mixed-gB and 14 days in single-gB. There was significantly statistical difference between two groups (P < 0.05). Conclusion gB genotype may have an impact on CMV DNA load and treatment time in HSCT recipients with CMV infection.

[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.