Huan Chen

Peking University People's Hospital, Peping, Beijing, China

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Publications (140)219.86 Total impact

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    ABSTRACT: The clinical significance and prognostic impact of IRFR in pediatric recipients of haploidentical SCT are not clearly understood. Therefore, we attempted to determine how IRFR affects clinical outcomes in children. Clinical data from 100 consecutive pediatric patients (60 boys and 40 girls; median age, 12 yr [range, 2–18 yr] after haploidentical SCT between January 2010 and December 2012 were collected retrospectively. IRFR was described as unexplained fever (>38 °C) within 24 h after the infusion of haploidentical PBSCs. Thirty-eight (38.0%) cases met the criteria for IRFR. ES was found in 24 (63.2%) of the 38 children with IRFR, with the median time of developing ES of +9 (7–16) days, while only 15 (25.4%) of the 59 children without IRFR were found with ES (p < 0.001). Similarly, the cumulative incidence rates of grade II–IV aGVHD were 50.0% in the IRFR group and 29.3% (p = 0.012) in the non-febrile group. Multivariate analysis identified IRFR as the risk factor for ES and aGVHD. In the haploidentical setting, IRFR is associated with the development of ES and aGVHD. We attempted to determine how IRFR affects clinical outcomes in children after haploidentical SCT. Thirty-eight children comprised the IRFR group, and 59 were in the control (non-IRFR) group. High incidence of ES was observed in children with the occurrence of IRFR. Similarly, the incidence of stage I–IV and II–IV aGVHD was significantly higher in the febrile group. Multivariate analysis showed IRFR to be the risk factor for ES and aGVHD.
    No preview · Article · Aug 2015 · Pediatric Transplantation
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    ABSTRACT: The preemptive therapy is an effective approach for CMV control; however, refractory CMV still occurred in a considerable group of recipients post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Until now, hardly any data have been available about the clinical characteristics and risk factors of refractory CMV, nor its' potential harmful impact on the clinical outcome following allo-HSCT. We studied transplant factors affecting refractory CMV in the +100 days post allo-HSCT and the impact of refractory CMV on the risk of CMV disease and non-relapse mortality (NRM). We retrospectively studied 488 consecutive patients with CMV infection post allo-HSCT. Patients with refractory CMV in the +100 days post allo-HSCT had a higher incidence of CMV disease and NRM than did those without refractory CMV (11.9% vs. 0.8% and 17.1% vs. 8.3%, respectively). Multivariate analysis showed that refractory CMV infection in the +100 days post allo-HSCT was an independent risk factor for CMV disease (HR=10.539, 95% CI 2.467-45.015, p=0.001) and that during the +60-+100 days was an independent risk factor of NRM (HR=8.435, 95% CI 1.511-47.099, p=0.015). Clinical factors impacting the risk of refractory CMV included receiving transplantation from HLA-mismatched family donors (HR=2.012, 95% CI 1.603-2.546, p<0.001), as well as acute GVHD (HR=1.905, 95% CI 1.352-2.686, p<0.001). We conclude that patients with refractory CMV during the early stage post allo-HSCT were at a high risk of both CMV disease and NRM. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jun 2015 · Clinical Microbiology and Infection
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    ABSTRACT: This study investigated the prognostic factors and clinical outcomes of preemptive chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion (Chemo-DLI) according to minimal residual disease (MRD) status in acute leukemia and myelodysplastic syndromes patients who received allogeneic hematopoietic stem cell transplantation (HSCT) (n = 101). Patients received immunosuppressive drugs to prevent graft-versus-host disease (GVHD) after Chemo-DLI. The 3-year cumulative incidences of relapse, non-relapse mortality, and disease-free survival (DFS) after HSCT were 39.5%, 9.6%, and 51.7%, respectively. The cumulative incidences of relapse and DFS were significantly poorer in patients who exhibited early-onset MRD. Forty-four patients turned MRD negative 1 month after Chemo-DLI; their cumulative incidences of relapse and DFS were significantly better than those with persistent MRD 1 month after preemptive Chemo-DLI (relapse: 19.8% vs. 46.8%, P = 0.001; DFS: 69.6% vs. 46.4%, P = 0.004). The cumulative incidences of relapse and DFS after HSCT were significantly better in patients with chronic GVHD (cGVHD) than those without cGVHD (relapse: 19.6% vs. 63.7%, P < 0.001; DFS: 74.4% vs. 23.8%, P < 0.001). Early-onset MRD, persistent MRD after Chemo-DLI, and non-cGVHD after Chemo-DLI, which were associated with increased relapse and impaired DFS, suggest unsatisfactory response to preemptive Chemo-DLI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · European Journal Of Haematology
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    ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post-consolidation therapy and curative option for adult patients with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) is one of the most important alternative sources for those without HLA-identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in adult Ph-negative ALL CR1 patients (n=183). We produced an unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor (G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin, and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high-risk versus low-risk groups were 29 versus 23 years. Three-year incidences of relapse mortality and nonrelapse mortality for high-risk versus low-risk groups were 7.1% versus 11.1% (P = 0.498) and 18.0% versus 16.2% (P = 0.717), respectively. Three-year probabilities of disease-free survival and overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% (P = 0.896) and 74.9% versus 72.7% (P = 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high- and low-risk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be considered for adults with Ph-negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Apr 2015 · International Journal of Cancer
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    ABSTRACT: We aimed to analyze the complications and survival associated with myeloablative haploidentical SCT in patients aged ≥50 years, and compare these results with a younger group population. In this case-control study, enrolled patients with leukemia were identified from 1262 patients between May 2002 and May 2013 at a single institution. Thirty-one patients were aged ≥50 years (the older group) and 165 patients were aged 18-49 years (the younger group). Of the older group, 20 out of 31 (64.5%) had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 2. Statistical analysis showed no significant differences in the incidences of grades II to IV acute GVHD, extensive chronic GVHD, and non-relapse mortality (NRM), or probability of relapse between the two groups. Furthermore, the 3-year overall survival (OS) and leukemia-free survival (LFS) were not significantly different between the older and younger groups: 67.0% ± 9.3% vs. 75.3 ± 3.4% (P = 0.406) and 60.5% ± 9.6% vs. 72.5% ± 3.5% (P = 0.183), respectively. Selected older patients aged ≥50 years with low HCT-CI and good performance status could safely undergo haploidentical SCT. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Mar 2015 · Clinical Transplantation
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    ABSTRACT: 86 adult inv(16) acute myeloid leukemia (AML) patients in the first complete remission (CR1) were serially monitored for CBFB-MYH11 transcript levels during the early courses of chemotherapy. 57 and 29 of them received chemotherapy/autologous SCT and allo-SCT after the second consolidation, respectively. For patients receiving chemotherapy/autologous SCT, the sole independent adverse prognostic factor for the cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) was a CBFB-MYH11 level >0.2% after course 2 consolidation (p=0.003, 0.003 and 0.031), which was used to define a poor molecular response (MR). allo-SCT significantly decreased the 3-year CIR and increased the DFS and OS of patients with a poor MR (p<0.0001, 0.0001 and 0.045) but did not improve the outcome of good-MR patients (all p>0.05) compared with chemotherapy/autologous SCT. Therefore, allo-SCT could improve the outcome of adult inv(16) AML patient in CR1 with a poor MR during the early courses of chemotherapy.
    No preview · Article · Mar 2015 · Leukemia & lymphoma
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    ABSTRACT: The role of haploidentical related allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is not clear. We aimed to investigate the long-term survival of Ph+ ALL patients who underwent haploidentical donor (HID)-HSCT and to analyze the factors influencing relapse and survival after allo-HSCT. The study population included Ph+ ALL patients who underwent haploidentical related allo-HSCT. Additionally, Ph+ ALL patients who underwent human leukocyte antigen (HLA)-matched related donor (MRD) transplants during the same period were included to compare outcomes. BCR-ABL transcript levels were analyzed by using real-time quantitative reverse transcription polymerase chain reaction. Clinical data of 139 Ph+ ALL patients received allo-HSCT in our center was analyzed. Of these patients, 101 received HID transplants and 38 received MRD transplants. At a median follow-up of 36 months, the 5-year disease-free survival (DFS) and overall survival (OS) in the HID transplant group were 65.8% and 74.0%, respectively. The 5-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) for the HID transplant group were 20.3% and 15.6%, respectively. In addition, there were no differences in OS, DFS, CIR, and NRM between the HID and MRD groups. Multivariate analysis showed that imatinib resistance was a significant factor influencing DFS and CIR in HID transplant patients. Haploidentical HSCT for the treatment of Ph+ ALL achieves promising long-term survival, which is comparable to that of HLA-matched related HSCT. Imatinib resistance is a negative predictor of relapse and DFS after allo-HSCT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Feb 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation

  • No preview · Article · Feb 2015 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: To explore the efficacy and safety of expanding cytomegalovirus specific cytotoxic T lymphocytes (CMV-CTL) in vitro on refractory cytomegalovirus (CMV) infection. A total of twenty-eight patients with refractory CMV infection following stem cell transplant (SCT) were treated with CMV-specific T cells, of which 19 cases were from hematopoietic stem cell donors and 9 from third-party donors. In the first course, CTL was infused once or twice and the efficacy and adverse effects were evaluated. If CMV infection relapsed after complete remission (CR), the second course would be given. Twenty-one patients with refractory CMV viremia and seven with CMV diseases were eligible for adoptive T-cell transfer. After a median of 76 (39-321) days post-transplant, patients received a median dose of 1.0 (0.5-10.0) × 10(7) CTL infusion in the first course. All twenty-one patients with CMV viremia and four patients with CMV diseases achieved CR after using 9 (3-23) and 7 (4-18) days respecitvely. Six patients with CMV viremia and one with CMV disease received the second course after recurrence. Another four patients with viremia and one with CMV disease had reached CR again. Five patients exhibited graft-versus-host diseases (GVHD), all experiencing mild to moderate skin involvement. Six patients died of CMV infection and 2 of other transplantation-related complications. Our preliminary results have shown that CMV-CTL infusion is effective against refractory cytomegalovirus infection following SCT, but therapeutic schedule still needs to be improved in further study.
    No preview · Article · Feb 2015 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
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    ABSTRACT: Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p < 0.01) or patients without aGVHD (41.40 ng/ml, p < 0.05). Allografts, including granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cell (PBPC) and G-CSF-primed bone marrow (GBM), from 38 patients were analyzed for IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.
    No preview · Article · Dec 2014 · Annals of Hematology
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    ABSTRACT: We examined the incidence, risk factors, treatment, and clinical outcomes of extramedullary relapse (EMR) in 961 acute leukemia patients undergoing human leukocyte antigen-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between 2002 and 2013. Multiple controls were selected at random from the same cohort and matched to EMR cases for diagnosis, disease status at HSCT, age at the time of the HSCT, and year of the HSCT. Forty patients exhibited EMR with a median time to EMR of 207 days. The cumulative incidence of EMR was 4.0% at 3 years, and the incidence was higher in acute lymphoblastic leukemia patients compared to acute myeloid leukemia patients (5.6% vs. 2.4%). In the multivariate analysis, non-complete remission (CR) status at HSCT (hazard ratio [HR]=4.6; P=0.018) and non-chronic graft-versus-host disease after HSCT (HR=3.2; P<0.001) were the independent risk factors for EMR after haplo-HSCT. A total of 27 patients received combination treatments, and the proportion of patients who achieved CR was higher than those who received single treatment. Multifocal involvement at EMR (HR=2.7; P=0.024) and non-CR after EMR treatments (HR=4.6; P<0.001) were the independent risk factors for poor survival rates among EMR patients. We found that graft-versus-leukemia effect may help to prevent EMR after haplo-HSCT.
    No preview · Article · Dec 2014 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: Background: In haploidentical hematopoietic stem cell transplantation (HSCT), the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD. However, the successful application of modified DLI depended not only on the reduction of severe GVHD, but also on the preservation of graft-versus-leukemia (GVL) effect. Therefore, this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT. Methods: A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively. Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks. Results: First, compared with prophylaxis for <6 weeks, prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs. 69.0%, P < 0.001). Besides, prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P = 0.018) and in 49 patients developing MRD-positive status post-transplant (P < 0.001). Second, prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P < 0.05), reduced the therapeutic application of immunosuppressive agents (P = 0.019), but increased the incidence of chronic GVHD (P < 0.05). Third, prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients, as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P < 0.05). Conclusions: In haploidentical HSCT, prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect, but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks. This strategy will probably improve the safety and efficacy of modified DLI further.
    No preview · Article · Oct 2014 · Chinese medical journal
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    ABSTRACT: To investigate the impact of body mass index (BMI) before transplantation on clinical outcomes of haploidentical allogeneic stem cell transplantation (allo-HSCT). We performed a retrospective cohort study of 253 adult patients with acute or chronic leukemia who received haploidentical allo-HSCT from August 2008 to September 2011. All conditioning regimens were myeloablative and bulsufan based. Patients were stratified according to BMI values (low BMI group: <18 kg/m(2); normal BMI group: ≥ 18 and < 25 kg/m(2); overweight BMI group: ≥ 25 kg/m(2)). Other possible risk factors correlated with GVHD, relapse, transplant related mortality (TRM) and overall survival (OS) included age and gender of donor and recipient, HLA disparity, relationship between donor and recipient, diagnosis, status of disease, ATG dose in conditioning regime(10 mg/kg , 6 mg/kg), mononuclear cells (MNC), CD(+)34 and CD(+)3 cell amount from granulocyte colony-stimulating factor (G-CSF) primed bone marrow grafts (G-BM) and G-CSF mobilized peripheral blood grafts(G-PB). Cox regression analysis was used to determine the related risk factors. The median age of all 253 patients was 31 (18-56) years, including 128 cases with acute myeloid leukemia (AML), 95 cases with acute lymphocytic leukemia (ALL), and 30 cases with chronic myeloid leukemia (CML). According to primary diseases, 185 patients were classified in the standard -risk group and 68 cases in the high-risk group. Median follow-up time was 929 days (range: 48-1762 days) post-transplantation. Engraftment has been attainted 252 (99.6%) recipients with the median time of granulocyte and platelet recovery 12 days (ranging from 9 to 45 days) and 16 days (ranging from 7 to 180 days), respectively. Cumulative incidences of acute GVHD was 33.2% with median time of 25 days (range: 13-88 days) after transplant. Multivariate analysis identified that low BMI was associated with an increased risk of grade III-IV acute GVHD (HR = 5.736, 95%CI 1.779-18.491, P = 0.003). There was no significant impact of BMI to other manifestations of GVHD, TRM, relapse or OS in different groups. Our findings demonstrate a correlation between pre transplant BMI and clinical outcome post-transplant. Low BMI was associated with increased risk of severe acute GVHD in leukemia patients receiving haploidentical allo-HSCT. Meticulous supportive care pre-transplantation is required for low BMI patients.
    No preview · Article · Sep 2014 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
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    ABSTRACT: Objective: To improve the understanding of treatment for graft failure by analyzing the efficacy of second transplantation for graft failure after first allogeneic stem cell transplantation (allo-HSCT). Methods: Twenty-two patients encountered graft failure after first allo-HSCT from Peking University Institute of Hematology were retrospectively reviewed. The incidence of re-engratment, graft versus host disease (GVHD) and overall survival (OS) was analyzed. Also the factors associated with re-engraftment and OS were analyzed in multivariate model. Results: Twenty-two patients encountered graft failure, including 12 primary graft failure and 10 secondary graft failure. 13(59.1%) patients acquired engraftment. And 13 patients acquired neutropil engraftment with median time of 15 (7-26) days, while 9 patients acquired platelet engraftment with median time of 12 (7-14) days. None of the factors included in mulivariate analysis showed impact on engraftment. The treatment related mortality at 100 day and 3 years after second transplantation was 40.9% and 72.7%, respectively. The main cause of death was infection (13/17). The 3-year OS was 22.7%, and the main cause of death was infection (13/17). The factors associated with OS included primary graft failure [P=0.001, HR 40.207 (4.828-334.868)] and receiving second transplantation in 60 days after first transplantation [P=0.003, HR 12.340 (2.290-66.498)]. Conclusion: Second transplantation may be an effective salvage choice for graft failure. However, the efficacy was far from satisfactory.
    No preview · Article · Aug 2014 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: Objective: Post-transplant lymphoproliferative disorder (PTLD) occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. Risk factors including pre-HSCT exposure variables, conditioning regimens, transplant-related complications, and post-HSCT immune reconstitution were investigated in the development of PTLD after allo-HSCT. Methods: A nested case-controlled study was designed. Patients diagnosed with PTLD and controls match for time were identified from a cohort of 1 184 patients who underwent haploidentical HSCT between 2006 and 2012 for hematologic malignancies. Results: There were 12 PTLD patients with median time to diagnosis 63.5 d (45-360 d) post-HSCT. The pre-HSCT exposure variables, conditioning regimens and transplant-related complications of the two groups had no statistical difference. Similar rates of graft versus host disease (GVHD) and cytomegalovirus (CMV) infection were seen in both groups. But the absolute count of CD⁺₁₉ cells, CD⁺₃ cells, CD⁺₄ cells and CD⁺₈ cells at day 30 after HSCT, the serum IgG and IgM were much higher in the control group. In multivariate analysis, absolute count of CD⁺₄ cells lower than 0.019 9×10⁹/L (OR = 6.71, 95% CI 1.42-31.25, P = 0.016) at day 30 after HSCT was an independent risk factor for PTLD. Two cases (3.03%) of PTLD occurred in the low risk group (absolute count of CD⁺₄ cells ≥ 0.019 9 ×10⁹/L), the other 10 cases (15.15%) in the high risk group (absolute count of CD⁺₄ cells < 0.019 9 × 10⁹/L). Conclusions: Patients with delayed immune reconstitution are at higher risk of developing PTLD after allo-HSCT. Improving the early immune reconstitution may help to decrease the incidence of PTLD after haploidentical HSCT.
    No preview · Article · Jul 2014 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
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    ABSTRACT: Background: Minimal residual disease (MRD)-directedmodified donor lymphocyte infusion (mDLI) is used to treat relapse after hematopoietic stem cell transplantation (HSCT). For patients who experience an unsatisfactory response tomDLI, relapse is usually inevitable. Therefore, we sought to evaluate the efficacy ofinterferon α therapy in these patients. Methods: Regular MRD monitoring was carried out after the HSCT. The patients who were MRD-positive underwent mDLI. Patients with an unsatisfactory response to mDLI received interferon α therapy (3 million units, twice weekly) with regular monitoring of MRD. To ensure the immunomodulatory effects of interferon α, immunosuppressant treatment would be stopped before interferon α treatment. Results: Five patients with an unsatisfactory response to mDLI treatment received interferon α (3 had t (8;21) chromosomal translocation acute myeloid leukemia, and 2 had common acute leukemia). They had significantly reduced or resolved MRD. Four patients developed chronic graft-versus-host disease. Two of the 5 patients reported transient fevers, and no significant bone marrow suppression was observed. All of them were in continuous complete remission after interferon a treatment. The median survival time was 469 days (range 368-948 days). Conclusions: In patients with an unsatisfactory response to MRD-directed mDLI, interferon a may directly or indirectly induce the graft-versus-leukemia effect to improve mDLI efficacy and clear MRD.
    No preview · Article · Jul 2014 · Chinese medical journal
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    ABSTRACT: The best donor for a related donor for a HLA-haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant recipients treated on a uniform protocol. Younger donors and male donors were associated with less non-relapse-mortality (NRM; hazard ratio [(HR)=0.30; 95% confidence interval [CI] 0.01-0.39; P=0.008 and HR 0.65, 95% CI, 0.49-0.85; P=0.002) and better survival (HR=0.73; 95%CI, 0.54-0.97; P=0.033 and HR=0.73; 95%CI, 0.59-0.91; P=0.005). Father donors were associated with less NRM (HR=0.65; 95%CI, 0.45-0.95; P=0.02), acute graft-versus-host disease (GvHD) (HR=0.69; 95% CI, 0.55-0.86; P=0.001) and better survival (HR=0.66; 95%CI, 0.50-0.87; P=0.003) compared with mother donors. Children donors were associated with less acute GvHD than sibling donors (HR=0.57; 95% CI, 0.31-0.91; P=0.01). Older sister donors were inferior to father donors with regard to NRM (HR=1.87; 95%CI, 1.10-3.20; P=0.02) and survival (HR=1.59; 95%CI, 1.05-2.40; P=0.03). Non-inherited-maternal-antigen (NIMA)-mismatched sibling donors were associated with the lowest incidence of acute GvHD compared with parental donors and non-inherited-paternal-antigen (NIPA)-mismatched sibling donors. Specific HLA-disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA-haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.
    Preview · Article · Jun 2014 · Blood
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    ABSTRACT: We compared total body irradiation (TBI,700 cGy)/cyclophosphamide (Cy,3.6g/m(2))/simustine (250mg/m(2)) plus anti-thymocyte globulin (ATG) (TBI/Cy plus ATG) with cytarabine (8 g/m(2))/intravenous busulfan (Bu,9.6mg/kg)/Cy (3.6g/m(2)) /simustine (250mg/m(2)) plus ATG (modified Bu/Cy plus ATG) as preparative therapy in T-cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia. From August 2009 to August 2013, 38 consecutive patients using TBI/Cy plus ATG regimen for T-cell-replete haplo-HSCT (TBI group) at our center were eligible, which contained 28 high-risk and 10 standard-risk patients. A nested case-control study was designed. Seventy-seven patients using modified Bu/Cy plus ATG regimen (Bu group) were randomly selected in a 1-3:1 ratio with matching for age, the disease and status, the year of HSCT (±2 years) and the length of follow-up. Only one graft failure occurred in TBI group. The incidence and time of neutrophil and platelet engraftment were comparable between the two groups. Severe grade III/IV GVHD was observed in 13.4% of Bu group and only 2.6% of TBI group (P=0.083). More toxicity of the liver (37.7% vs. 10.5%; P=0.002) and more hemorrhagic cystitis occured in Bu group (49.3% vs. 23.7% ,P=0.008). Diarrhea was more common in TBI group (44.7% vs. 22.1%; P= 0.031). There was no significant difference in the 2-year incidences of relapse (26.5 % for TBI group vs. 32.3 % for Bu group, P=0.742), the 1-year transplant-related mortality (12.6% vs. 16.2 %, P=0.862), the 2-year overall survial (60.2% vs. 57.0%, P=0.937) and the 2-year incidence of disease-free survial (57.9 % vs. 56.6 %, P=0.845) between the two groups.We conclude that the TBI/Cy plus ATG regimen seems to be feasible in T-cell-replete haplo-HSCT, with promotes stable engraftment,a lower incidence of liver toxicity and hemorrhagic cystitis.However, longer follow-up is necessary to determine the late relapse rate and late toxicity.
    No preview · Article · Apr 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: To compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with chemotherapy alone in adult standard-risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1). Consecutive 138 adult patients with standard-risk ALL in CR1 were retrospectively investigated. Out of these patients, 59 received chemotherapy alone (Group A), and 79 received unmanipulated haploidentical HSCT (Group B). Cumulative incidence of relapse at 5 years in Group A was significantly higher than Group B (66.3%vs.29.9%,P<0.0001). The OS and DFS in Group A were significantly inferior to Group B (P<0.0001). Moreover, multivariate analyses demonstrated that central nervous system leukemia (P=0.002), T-cell immunophenotype (P=0.044), expression of E2A-PBX1 (P=0.007) and minimal residual disease-positive after the 1(st) cycle of consolidation (P=0.004) were correlated with relapse. Patients with one of four risk factors were assigned to high-risk group. Otherwise, patients without risk factors were assigned to low-risk group. In high-risk group, HSCT had lower relapse rate and superior DFS compared with chemotherapy (P<0.05), but in low-risk group, there were no differences between HSCT and chemotherapy (P>0.05). This study is the first to demonstrate that, compared with chemotherapy alone, haploidentical HSCT is a better post-remission therapy in adult standard-risk ALL in CR1. Moreover, based on the four risk factors, the establishment of risk-stratification could identify the subgroup of patients with higher risk of relapse in adult standard-risk ALL in CR1. Furthermore, risk-stratification directed post-remission therapies using haploidentical HSCT or chemotherapy alone not only reduce relapse rate, but also avoid unnecessary treatment-related mortality and improve survival.
    No preview · Article · Apr 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: To compare the clinical characteristics and prognosis of acute graft-versus-host disease (aGVHD) between patients undergoing human leukocyte antigen (HLA)-identical and HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). Cinical data of 544 patients receiving related allo-HSCT in Institute of Hematology of Peking University from January 2010 to December 2011 were retrospectively analyzed. The clinical features of aGVHD including manifestations and prognosis between HLA-identical and HLA-mismatched transplantation were compared. The cumulative incidence of aGVHD in related HLA-mismatched transplant was 50.2%, which was significantly higher than that of HLA-identical transplant (20.4%, P < 0.001). However, the cumulative incidence of grade III°-IV° aGVHD between the two groups was comparable (4.5% vs 6.8%, P = 0.066). Gut aGVHD accounted for 31.1% in HLA-identical transplant while cutaneous aGVHD was the dominant area in HLA-mismatched transplant (66.5%). The incidence of gut and liver aGVHD in HLA-mismatched patients was also lower than that in HLA-identical patients. The proportion of patients with aGVHD accompanied by fever was higher in HLA-mismatched patients than in HLA-identical patients (47.6% vs 28.9%, P = 0.028). The cure rate of aGVHD in identical transplant was lower than that in mismatched transplant, especially for grade III°-IV° aGVHD. The complete remission rate after second-line anti-GVHD therapies was lower than that of mismatched transplant (88.9% vs 98.8%, P = 0.006). More patients died of aGVHD in identical transplant compared with mismatched transplant (11.1% vs 2.4%, P = 0.024). More patients who received HLA-mismatched allo-HSCT develop into aGVHD compared with HLA-identical transplant. But the incidence of severe aGVHD between HLA-identical and -mismatched is comparable. The overall cure rate of HLA-mismatched transplant is significantly higher than that of HLA-identical transplant.
    No preview · Article · Mar 2014 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]