Objective To compare the clinical features of cytomegalovirus (CMV) infection and CMV disease after allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA haploidentical related doors vs.HLA-matched sibling donors.Methods A total of 327 patients who received allogeneic HSCT from Jan.2011 to Dec.2011 were enrolled.There were 312 patients who had complete serological data before HSCT including 216 cases of HLA haploidentical related HSCT and 96 cases of HLA-matched sibling HSCT.Monitoring of CMV antigenemia was performed by using real-time quantitative (RQ) PCR after transplantation.Risk factors were compared by univariate and multivariate analysis.Results The cumulative incidence of CMV infection and CMV disease was (80.1 ± 2.7) ％ and (8.7 ± 2.0) ％ in HLA haploiddentical HSCT group,and (21.1 ± 4.9) ％ and 0 in HLA-matched sibling HSCT group respectively,and the difference was statistically significant between the two groups (P＜0.01).Univariate analysis revealed that HLA haploidentical related HSCT,less than 20 years of age,high risk disease,CMV-IgG serum positivity in patients or donors,acute graft-versus-host disease (aGVHD),EB viremia,and hemorrhagic cystitis were the risk factors of CMV infection.HLA haploidentical related SCT and hemorrhagic cystitis were the risk factors for CMV disease.Multivariate analysis showed that patients less than 20 years of age had a significantly high incidence of CMV infection.Patients from HLA-matched sibling HSCT,low risk disease,aGVHD,hemorrhagic cystitis had a significantly low incidence of CMV infection.Conclusion Compared with patients receiving HLA-matched sibling HSCT,those who received HLA haploidentical related HSCT had significantly high incidence of CMV infection and CMV disease,which were correlated with incidence of hemorrhagic cystitis.

Objective: To explore the relation of the serum level of sIL-2R in relapse patients with acute lymphoblastic leukemia(ALL). Methods:With ELISA, we determined the levels of sIL-2R of 48 patients with ALL after their first diagnoses,complete remission 1 and relapse. The levels of sIL-2R of 30 patients from complete remission 1 to relapse were monitored. Results: The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the control. The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the complete remission 1 group. However,the difference between the complete remission 1 and the control had no statistical significance. When we determined the levels of sIL-2R dynamically, we found that after complete remission ,the levels of sIL-2R decreased,however, before one month of hematological relapse, the levels of sIL-2R increased. Conclusion: Monitor of the level of sIL-2R can predict impending relapse of patients with ALL and is helpful to early diagnosis of relapse.

Objective To investigate the incidence and pathogenesis of fever within the first 24　hours following allogeneic peripheral stem cell transfusion and to analyze the associated risk factors.Methods Totally 114 patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT)between October 2009 and August 2010 were enrolled and clinical data of febrile patients within 24 hours　following peripheral stem cell transfusion were retrospectively analyzed.Multivariate logistic regression analysis was performed to identify the risk factors for transfusion related fever.Results Thirty-two (28.1％)out of the 114 patients had a fever within 24 hours after allo-HSCT.All of them were human leukocyte antigen(HLA)mismatch transplantation.The median time of the temperature elevated was 2.5(0-18.0)hours after the infusion with a median time of the peak of 7.8(3.5-23.0)hours after the infusion.Fever was attributed to definite infection in 6 patients and no definite infection in the remaining 26 patients.None of them were hemolytic,which was attributed to transfusion related fever.Multivariate analysis showed that female donor and high count of peripheral leukocyte of donor peripheral blood were significant predictors for transfusion related fever.Conclusions Most of post-infusion fever within 24 hours after HLA mismatch related transplantation has no identifiable infectious focus.The risk factors for transfusion related fever are female donor and high number of peripheral leukocyte of donor blood.

Objective: To investigate the impact of mycophenolate mofetil (MMF) prophylaxis duration on acute graft-versus-host disease (aGVHD) after haploidentical stem cell transplantation (haplo-HSCT) using 'Beijing Protocol’. Methods: Adult patients (≥14 years) received haplo-HSCT in Peking University Institute of Hematology from Sep, 2016 to Mar, 2017 were retrospectively reviewed if they fulfilled the criterias: ①diagnosed with hematological maligancies; ②standard-risk status at haplo-HSCT. A total of 237 patients [including 102 patients with long MMF duration (defined as started on day -9 with 100 mg/d, adjusted to 500 mg/d from day +30 and discontinued on day +45 to +60 or occurrence of CMV/EBV reactivation or late-onset hemorrhagic cytitis), and 135 patients with short MMF duration (defined as started on day -9 with 500 mg/d and discontinued on the day achieved neutrophil engraftment)] were reviewed. The incidence of aGVHD, virus infection and overall survival (OS) were compared between the two groups. Results: The median durations of MMF prophylaxis of long and short duration groups were 27(7-71) and 15(9-24) days, respectively after haplo-HSCT. There were no differences of baseline characteristics (including sex, patient age, disease, mismatched HLA loci, donor-recipient relation, donor-recipient sex and donor age) between the two groups. The incidences of the grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD in long and short duration groups were 31.1% versus 17.6% (P=0.018) and 7.4% verus 7.8% (P=0.900), respectively. The duration of MMF prophylaxis was not found to be associated with gradeⅡ-Ⅳ aGVHD by the multivariate analysis. There were no significant differences in terms of CMV viremia, EBV viremia, hemorrhagic cytitis and OS between the two groups. Conclusion Prophylaxis with short duration MMF in the setting of 'Beijing protocol’ haplo-SCT was not associated with increased acute GVHD with no impact on OS, which indicated that short duration MMF might be a feasible GVHD prophylaxis regimen.

Objective To investigate the safety and efficacy of second allogeneic hematopoietic stem cell transplantation for the relapsed hematologic malignancies. Methods The data of 25 relapsed patients received the second allogeneic transplantation as a salvage therapy in Institute of Hematology Peking University between October 1999 and March 2010 were analyzed retrospectively. Twenty-four patients relapsed at 8. 8 (1-55) months after the first transplantation, except one received the second transplantation as prophylaxis therapy. They received the second transplantation after 3(0. 3-20) months' therapy. The median time between the 2 transplants was 10. 6(0. 6-59. 0) months. Results Most of the patients were given the conditioning regimen including total body irradiation (TBI, 700-779 cGy) or modified busulfan and cyclophosphamide (BUCY, BU 12 mg). All patients survived more than 30 days and achieved sustained white blood cell engraftment. Sinus obstructive syndrome, irradiation dermatitis and acute myocardial infraction were occurred in 3 patients and recoverable. Until January 31 in 2011, with a median observation period of 9. 1 (2. 0-131. 1) months, 8 patients had been living with a overall survival (OS) of 30.9%.Twelve patients relapsed at a median 4. 4 months and 10 died of it. The other 7 patients died of transplant related complications. The non-relapsed mortality was 35. 1 %. The disease status at the 2nd transplantation was the only factor which effected the OS (P = 0. 009). Conclusions The second allogeneic transplantation is a viable option for patients relapsing after the first transplantation. Reduced intensive conditioning regimen ensures the graft engraftment and reduces transplant related toxicity.

Objective To investigate the efficacy and safety of rituximab on Epstein-Barr virus (EBV) disease post allogeneic hematopoietic stem-cell transplantation.Methods A retrospective analysis was performed based on clinical data of 26 patients diagnosed as EBV disease and received rituximab from June 2006 to March 2012 in People's Hospital,Beijing University.Eleven patients were diagnosed as posttransplant lymphoproliferative disorders (PTLD) by histopathology and remaining 15 were diagnosed as probable EBV disease.Patients received a rituximab dose of 375 mg/m2 once a week.Efficacy was evaluated as revised response criteria for non-hodgkin lymphoma (NHL),and side effects during infusion were evaluated by Common Terminology Criteria for Adverse Events.Results Patients received 78 infusions with a median of 3 (1-6) infusions in each.There were no severe side effects during the infusion of rituximab.The 1st,2nd,3rd,4th,8th week cumulative complete remission (CR) were (11.5 ± 6.3)％,(42.2 ±10.2) ％,(64.4 ± 10.0) ％,(74.6 ± 9.4) ％,(87.3 ± 7.9) ％,respectively.The overall response rate was 84.5％,and the CR rate was 73.1％.The CR rate was higher among patients with single organ involved than those with multiple organs involved (10/10 vs 9/16,P =0.023).The CR rate was higher in patients with probable EBV disease than those with PTLD (13/15 vs 6/11,P =0.095),while there was no statistically significant difference.The incidence of one-year and two-year overall survival since onset of rituximab were (55.7 ± 10.2)％ and (39.6 ± 12.4)％,respectively.Survival rate was higher among the patients with single organ involved than those with multiple organ involved (8/10 vs 5/16,P =0.041).Survival rate was higher in patients with probable EBV disease than those with PTLD(11/15 vs 2/11,P =0.015).Conclusions Rituximab appears to be safe and effective for EBV disease.Due to a potential good response in probable EBV disease,we suggest rituxmab should be given based on probable EBV disease;meanwhile the pathological results should get early if possible.Prospective trial is needed to provide evidence so as to define optimal therapy of rituxmab.

Objective: To evaluate the impact of pre-transplant course on transplant outcomes in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis was conducted in 107 patients with AML who received allogeneic hematopoietic stem cells transplantation (allo-HSCT) in the first complete remission stage (CR₁) from January 2012 to June 2014. Results: ①46 cases received allo-HSCT within 6 months upon diagnosis, including 25 males and 21 females, with a median age of 26 (12-60) y. 61 cases received allo-HSCT after 6 months upon diagnosis, including 34 males and 27 females, with a median age of 31 (14-58) years. There is no statistical significance in patients’ age, gender, NCCN risk stratification, courses for induction, minimal residual disease (MRD) status, transplantation type and infection rates prior to transplantation. Total courses of chemotherapy before allo-HSCT were 4 (3-5) and 5 (4-10) for the two groups, respectively. ②Incidences of Grade Ⅱ-Ⅳ aGVHD were 26.09% (12/46) for the <6-month group and 24.59% (15/61) for the ≥6 months group (P=0.860) . Incidences of Grade Ⅲ/Ⅳ aGVHD were 2.17% (1/46) for the <6-month group and 14.75% (9/61) for the ≥6 months group (P=0.027) . ③ Probabilities of 2-year overall survival (OS) were (90.3±4.6) % for the <6 months group and (75.7±5.7) % for the ≥6 months group (P=0.042) . Probabilities of 2-year disease-free survival (DFS) were (90.7±4.4) % for the <6 months group and (76.3±5.5) % for the ≥6 months group (P=0.038) . ④ During the median follow-up of 863 (26-2 026) days, cumulative incidences of non-relapse mortality were (4.4±3.1) % for the <6 months group and (18.2±5.0) % for the ≥6 months group (P=0.047) . ⑤ Univariate analysis showed that age, NCCN risk stratification, MRD status before transplantation and rates of infection was not related to transplantation outcomes. Chemotherapy courses before allo-HSCT (≤4 or >4) was related to OS and DFS (P=0.044, P=0.039) , but not to NRM (P=0.079) . Conclusion AML patients who obtained CR₁ could achieve better long-term survival by receiving allo-HSCT within 6 months after diagnosis.

Objective: To investigate the clinical significance of PCR detection of human herpesvirus 6 (HHV6) in gastro biopsy on the course of diarrhea in patients with severe diarrhea after allogeneic hematopoietic stem cell transplantation (HSCT) . Methods: Data from a cohort of 45 HSCT recipients (including age, sex, transplantation conditions, graft-versus-host disease, treatments, clinical signs, outcome, HHV6, and other infections) performed between 2015 and 2016 were collected. Univariate analysis was used to evaluate influences between the different parameters. Results: Of the 45 enrolled recipients, 21 patients (46.7%) presented HHV6 positive in gastro-biopsy during the analyzed period. The incidence of CMV viremia in the positive HHV6 group was comparable with that in the negative HHV6 group. But the incidence of EBV viremia in the positive HHV6 group was significantly higher than in the negative HHV6 group (P=0.028) . 44 out of 45 patients with severe diarrhea were given antiviral treatment with foscarnet and/or ganciclovir, the latter didn’t influence the course of the diarrhea. Conclusions Positive PCR results in GI tract samples didn’t necessarily reflect reactivation of HHV6. Further studies are needed to define the significance of HHV6 for GI tract symptoms after allo-HSCT.

Objective:Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT.Methods:Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People′s Hospital from March 2013 to March 2020, which was defined as D -/R + group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D +/R + group). Results:Patients in D -/R + group developed CMV DNAemia later than patients in the D +/R + group (+37 days vs. +31 days after allo-HSCT, P=0.011), but the duration of CMV DNAemia in D -/R + group was longer than that of D +/R + group (99 days vs. 34 days, P=0.012). The rate of CMV reactivation 4 times or more in D -/R + group was 4/16, significantly higher than that of D +/R + group (4.7%, 3/64, P=0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, P=0.021) and CMV disease (4/16 vs. 4.7%, P=0.01) in D -/R + group were both higher than those in D +/R + group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D -/R + group was more than that in D +/R + group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Conclusions:Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D -/R + group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.

Objective To investigate the threshold of cytomegalovirus (CMV) DNAemia for preemptive antiviral therapy in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Viral load between 1 × 103 copies/ml and 5× 103 copies/ml was defined as low viral load by real time Q-PCR.Clinical data and outcome were collected.Results A total of 95 allo-HSCT recipients with low viral load from September 2014 to February 2015 were recruited in this study.The control group included 37 patients who received preemptive initial antiviral therapy.The other 58 patients didn't received antiviral treatment after positive viremia was confirmed.During monitoring,CMV viremia was cleared spontaneously in 17 patients of study group.Among 41 patients with continuous positive viremia in study group,26 patients received antiviral therapy after second positivity including 18 with viral load ＞5 × 103 copies/ml,2 with fever but still low viral load,2 with hemorrhagic cystitis and low viral load,4 with continuous low viral load.Eleven patients received antiviral therapy after the third positivity including 5 with viral load ＞5×103 copies/ml,1 low viral load patient with fever and diarrhea,5 with continuous low viral load.Only 4 patients received antiviral therapy after the fourth positivity of ＞5× 103 copies/ml.In the study group,35 cases received ganciclovir and 6 cases received foscarnet.The incidence of neutropenia did not differ significantly between study and control groups [minimum of neutrophil count:(1.63±0.41)× 109/L vs.(1.58 ± 0.36) × 109/L].The proportion of viral load greater than 5 × 103 copies/ml in the first week was comparable in two groups.Successful viral clearance rate was not statistically different (P=0.87).Of all 95 patients,no CMV diseases developed,neither did patient die of CMV infection.Conclusions Spontaneous clearance of viremia occurs in some patients receiving allo-HSCT with low CMV viral load.Delayed antiviral treatment of continuous positive viremia does not prolong the whole treatment duration,neither contributes to the progression of CMV diseases.