Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Incidence and clinical characteristics of engraftment syndrome after syngeneic hematopoietic stem cell transplantation in patients with hematological diseases / 中华血液学杂志

Objective: To explore the incidence and clinical characteristics of engraftment syndrome (ES) after syngeneic hematopoietic stem cell transplantation (syn-HSCT) in patients with hematological diseases. Methods: The clinical data of 21 patients who received syn-HSCT at People's Hospital of Peking University from January 1994 to May 2018 were retrospectively analyzed. Results: Seven (33.3% ) of 21 patients developed ES. The onset of ES symptoms occurred at a median of 8 (range: 5-13) days after HSCT, and the diagnosis of ES occurred at a median of 10 (range: 7-14) days after HSCT. Steroids were administered immediately after the diagnosis of ES, the median time of symptom continuance was 2 (range: 1-5) days, and all patients showed complete resolution of ES symptoms. In the multivariate analysis, patients with acute myeloid leukemia and faster neutrophil reconstitution were the risk factors for ES (HR=15.298, 95% CI 1.486-157.501, P=0.022, and HR=17.459, 95% CI 1.776-171.687, P=0.014) . Meanwhile, there was no significant difference in the overall survival and disease-free survival between patients with ES and those without ES. Conclusion: A high incidence of ES was observed in syn-HSCT recipients. Moreover, the prognosis of ES was excellent.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Treatment responses, outcomes, and prognostic factors associated with them in patients with secondary acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate treatment responses, outcomes, and prognostic factors in adults with secondary acute myeloid leukemia (sAML) . Methods: Between January 2008 and February 2021, date of consecutive cases of younger than 65 years of adults with sAML were assessed retrospectively. Clinical characteristics at diagnosis, treatment responses, recurrence, and survival were evaluated. Logistic regression and Cox proportional hazards model were employed to determine significant prognostic indicators for treatment response and survival. Results: 155 patients were recruited, including 38, 46, 57, 14 patients belonging to t-AML, and AML with unexplained cytopenia, post-MDS-AML, and post-MPN-AML, respectively. In the 152 evaluable patients, the rate of MLFS after the initial induction regimen was 47.4%, 57.9%, 54.3%, 40.0%, and 23.1% in the four groups (P=0.076) . The total rate of MLFS after the induction regimen was 63.8%, 73.3%, 69.6%, 58.2%, and 38.5% (P=0.084) , respectively. Multivariate analysis demonstrated that male gender (OR=0.4, 95% CI 0.2-0.9, P=0.038 and OR=0.3, 95% CI 0.1-0.8, P=0.015) , SWOG cytogenetic classification into unfavorable or intermediate (OR=0.1, 95% CI 0.1-0.6, P=0.014 and OR=0.1, 95% CI 0.1-0.3, P=0.004) and receiving low-intensity regimen as induction regimen (OR=0.1, 95% CI 0.1-0.3, P=0.003 and OR=0.1, 95%CI 0.1-0.2, P=0.001) were typical adverse factors impacting the first CR and the final CR; PLT<45 × 10(9)/L (OR=0.4, 95%CI 0.2-0.9, P=0.038) and LDH ≥258 U/L (OR=0.3, 95%CI 0.1-0.7, P=0.005) were independent factors for CR. Among the 94 patients with achieving MLFS, 46 cases had allogeneic hematopoietic stem cell transplantation. With a median follow-up period of 18.6 months, the probabilities of relapse-free survival (RFS) and overall survival (OS) at 3 years were 25.4% and 37.3% in patients with transplantation, and in patients with chemotherapy, the probabilities of RFS and OS at 3-year were 58.2% and 64.3%, respectively. At the time of achieving MLFS, multivariate analysis revealed that age ≥46 years (HR=3.4, 95%CI 1.6-7.2, P=0.002 and HR=2.5, 95%CI 1.1-6.0, P=0.037) , peripheral blasts ≥17.5% at diagnosis (HR=2.5, 95%CI 1.2-4.9, P=0.010 and HR=4.1, 95%CI 1.7-9.7, P=0.002) , monosomal karyotypes (HR=4.9, 95%CI 1.2-19.9, P=0.027 and HR=28.3, 95%CI 4.2-189.5, P=0.001) were typical adverse factors influencing RFS and OS. Furthermore, CR after induction chemotherapy (HR=0.4, 95%CI 0.2-0.8, P=0.015) and transplantation (HR=0.4, 95%CI 0.2-0.9, P=0.028) were substantially linked to longer RFS. Conclusion: Post-MDS-AML and post-MPN-AML had lower response rates and poorer prognoses than t-AML and AML with unexplained cytopenia. In adults with male gender, low platelet count, high LDH, and SWOG cytogenetic classification into unfavorable or intermediate at diagnosis, and receiving low-intensity regimen as the induction regimen predicted a low response rate. Age ≥46 years, a higher proportion of peripheral blasts and monosomal karyotype had a negative effect on the overall outcome. Transplantation and CR after induction chemotherapy were greatly linked to longer RFS.

Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation / 中华医学杂志(英文版)

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Risk factors analysis for steroid-resistant acute graft versus host disease after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the risk factors of steroid resistant acute graft- versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of adult patients with acute myeloid leukemia (AML) /Myelodysplastic syndrome (MDS) who developed aGVHD after haplo-HSCT in Peking University Institute of Hematology from January 1st, 2010 to December 31st, 2012 were retrospectively reviewed. Results: A total of 85 patients were enrolled in the study, including 55 males and 30 females, with a median age of 30 (19-67) years. After steroid therapy, there were 53 (62.4%) , 6 (7.1%) and 26 (30.6%) patients achieved complete remission (CR) , partial remission (PR) and non-remission (NR) , respectively. The CR rates of the grade Ⅰ/Ⅱ and Ⅲ/Ⅳ aGVHD by steroid therapy were 66.2% (51/77) vs 25.0% (2/8) (χ(2)=3.639, P=0.048) , respectively. The CR rates of the patients with aGVHD involving 1 target organ and 2 target organs were 77.4% (48/62) vs 21.7% (5/23) (χ(2)=22.157, P<0.001) . The CR rates of patients with standard risk (SR) and high risk (HR) Minnesota risk score was 67.5% (52/77) vs 12.5% (1/8) (χ(2)=7.153, P=0.004) . The mononuclear cells≥8.33×10(8)/kg and the HR Minnesota risk score were independent risk factors for steroid-resistant aGVHD in multivariate analysis. Between Minnesota risk score SR (77 cases) and HR (8 cases) groups, the OS rates at 22 months after transplantation were (90.3±3.8) %vs (75.0±15.3) % (χ(2)=2.831, P=0.092) . After steroid treatment for aGVHD, the OS rates at 22 months in the CR group (53 cases) and non-CR group (32 cases) were (95.2±3.4) %vs (78.6±7.9) % (χ(2)=5.287, P=0.021) respectively. Conclusion: The Minnesota risk score and mononuclear cells count are effective tool for predicting steroid-resistant aGVHD after haplo-HSCT.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation / 中华医学杂志(英文版)

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.

Clinical analysis of hemorrhagic cystitis in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.

The comparison of predicting clinical outcomes between immunolophenotype and hematological complete remission before human leukocyte antigen-matched sibling donor transplantation in acute myeloid leukemia / 中华血液学杂志

Objective: To assess the prognostic significance of immunophenotype complete remission (ICR) and hematological complete remission (HCR) before human-leukocyte antigen (HLA)-matched sibling donor transplantation (MSDT) in acute myeloid leukemia (AML) patients. Methods: A cohort of 182 AML (non-APL) patients undergoing MSDT in HCR was retrospectively studied [including complete remission with ANC and PLT recovery (CR), CR with incomplete PLT recovery (CRp), CR with inconplete ANC and PLT recovery (CRi)]; ICR was determined as undetective minimal resudial disease (MRD) by multi-parameter flow cytometer. Results: ①Of the 182 patients, 97 were male, 85 female, and the median age was 41(4-62) years. ②The CR and CRi+CRp rates were 80.8% (147/182) and 19.2%(35/182), respectively; The 4-year cumulative incidence of relapse[CIR, (11.0±4.3)% vs (16.0±7.1)%, χ(2)=0.274, P=0.600], non-relapse mortality[NRM, (14.0±4.3)% vs (9.0±6.3)%, χ(2)=0.913, P=0.339], leukemia-free survival[LFS, (75.0±5.1)% vs (75.0±8.3)%, χ(2)=0.256, P=0.613], and overall survial [OS, (77.0±5.2)% vs (80.0±8.1)%, χ(2)=0.140, P=0.708] were comparable between the CRp+CRi and CR groups. ③Compared with the non-ICR group (n=35), the ICR group (n=147) showed lower 4-year CIR [(11.3±3.4) % vs (55.2±8.8) %, χ(2)=32.687, P<0.001], better 4-year LFS [(76.2±4.7)% vs (32.8±8.7)%, χ(2)=26.234, P<0.001] and OS[(79.0±4.7)% vs (39.0±9.1)%, χ(2)=25.253, P<0.001], and comparable NRM[(12.5±4.1)% vs (12.0±7.1)%, χ(2)=1.002, P=0.656]. ④Mulitvariate analysis confirmed the independent prognostic value of ICR in lower CIR [HR=11.026(95%CI 4.685-25.949), P<0.001], higher LFS [HR=5.785 (95% CI 2.974-11.254), P<0.001] and OS[HR=5.578 (95% CI 2.575-27.565), P<0.001]. Conclusion: The results indicated that ICR instead of HCR pre-transplantation had a significant prognostic value in AML patients undergoing MSDT.

Impact of mycophenolate mofetil prophylaxis duration on acute graft-versus-host disease after haploidentical stem cell transplantation / 中华血液学杂志

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.

Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia: a report of 12 patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse and survival of 12 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.</p><p><b>RESULTS</b>Twelve (7 males and 5 females) CMML patients with a median age of 39 years old received allo-HSCT including 7 from HLA-matched sibling and 5 from haploidentical related donors. All 12 patients achieved engraftment. The median time of neutrophil engraftment and platelet engraftment were 15 (11 - 20) days and 13 (11 - 18) days, respectively. 4 patients occurred acute GVHD, and 3 occurred chronic GVHD. After the median follow-up of 17.5 months (12 - 32 months), the overall survival, disease free survival and relapse rate were 66.7%, 66.7%, and 16.7%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT can improve the survival of patients with CMML, and is a effective therapy for CMML.</p>

The kinetics and prognosis of platelet reconstitution after unmanipulated haploidentical stem cell transplantation without in vitro T cell depletion / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the kinetics of platelet reconstitution and its prognostic significance in patients received unmanipulated haploidentical stem cell transplantation (Haplo-HSCT) without in vitro T cell depletion.</p><p><b>METHODS</b>A total of 291 patients received Haplo-HSCT without in vitro T cell depletion between January 2007 to December 2008 were retrospectively reviewed. They were categorized into 3 groups according to the platelet count on day 30, day 60 and day 90: (1) persistent thrombocytopenia (Group A) was defined as the platelet count never reached 50×10⁹/L on the three time points; (2) unstable thrombocytopenia (Group B): the platelet count recovered to a level of 50×10⁹/L by day 30 or 60 or 90, yet did not reach a level of more than 100×10⁹/L; (3) non-thrombocytopenia (Group C): the platelet count was higher than 100×10⁹/L on day 90. The kinetics of platelet reconstitution, overall survival (OS) and treatment related mortality (TRM) were compared between 3 groups.</p><p><b>RESULTS</b>Of the 291 consecutive patients, 288 cases engrafted successfully and 262 cases were platelet transfusion independent. The median intervals of neutrophil and platelet engraftment were 13 (9-29) days and 17 (7-180) days, respectively. The cumulative incidence of grade III-IV acute graft versus host disease (GVHD) on day 100 and chronic GVHD at 3 years were 14.7% and 56.4% respectively. OS and TRM at 3 years were 64.6% and 22.3% respectively. At the end of the follow-up, 266 cases were platelet transfusion independent: including 71 (24.4%) cases in Group A, 147 (50.5%) in Group B and 73 (25.1%) in Group C. OS in group A, B and C was 38.0%, 69.4% and 80.8% (P<0.05) respectively. TRM in Group A, B and C was 53.5%, 17.7% and 1.4% (P<0.05) respectively. Persistent thrombocytopenia was related with lower OS and higher TRM in multivariate analysis.</p><p><b>CONCLUSION</b>Persistent thrombocytopenia was common after Haplo-HSCT without in vitro T cell depletion, and patients with persistent thrombocytopenia have poor OS and higher TRM.</p>

The relationship between serum resistin level and blood sugar, blood lipids and thyroid hormone in patients with hyperthyroidism / 中国地方病学杂志

ObjectiveTo undertake a controlled, prospective study to investigate the relationship between serum resistin level and blood sugar, blood lipids and thyroid hormone in patients with hyperthyroidism. Methods Clinical data of 50 patients with hyperthyriodism were collected from 2008 to 2009 in department of endocrinology the Second Hospital of Harbin Medical University. All patients were newly diagnosed cases that received no medication. At the same time, 40 healthy persons underwent physical examination in the hospital were taken as control group. Diabetes, obesity, hypertension, and high cholesterol were excluded from the two groups. Serum resistin level was determined using ELISA method. Chemiluminescence was used to check the levels of fasting insulin, free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH). Glucose oxidase method determination-peroxidase-anti-peroxidase(GOD-PAP) was used to check the levels of fasting blood-glucose.Cholesterol oxidase method was used to check the levels of total cholesterol(T-CH). Glycerol-phosphate oxidase was used to check the levels of triglyceride(TG). Enzymes colorimetric method was used to check high density level of lipoprotein cholesterol(HDL-C) and low density level of lipoprotein cholesterol (LDL-C), and the height, weight,waist circumference, and hip circumference were measured. Body mass index (BMI) and insulin resistance index (HOMA-IR) were calculated. Groups were compared using t test and correlation analysis using Pearson correlation test, and the relationship between serum resistin level and blood sugar, blood lipids and thyroid hormone were analyzed using multiple linear stepwise regression analysis method. Results Serum glucose[(5.2 ± 0.7)mmol/L],resistin concentrations[(132.1 ± 41.3)μg/L], FT3[(19.8 ± 8.7) pmol/L], FT4[(54.1± 29.6)pmol/L], fasting insulin levels[(7.9 ± 2.8)mU/L] and HOMA-IR(2.3 ± 1.0) were significantly higher compared with controls group [(4.7 ± 0.5)mmol/L, (65.1 ± 5.9)μg/L, (4.1 ± 0.6)pmol/L, (14.3 ± 2.2)pmol/L, (6.4 ± 2.7)mU/L, (1.5 ±1.2); t =4.64, 10.17, 11.42, 8.49, 4.48, 9.42, P＜ 0.01 or ＜ 0.05)]. T-CH[(3.7 ± 0.8) mol/L], LDL-C[(1.8 ±0.6)mol/L], TSH[(0.01 ± 0.01 )mU/L] were significantly lower compared with controls group[(4.6 ± 0.7)mol/L,(2.3 ± 0.7)mol/L, (1.80 ± 0.90)mU/L; t =5.30, 3.33, 14.48; all P＜ 0.01)]. Pearson correlation analysis showed that resistin and FT3, FT4 and HOMA-IR was positively correlated, respectively (r =0.719, 0.790, 0.396, P ＜ 0.01or＜ 0.05), resistin and T-CH and LDL was negatively correlated, respectively(r =- 0.364, - 0.519, P ＜ 0.05or ＜ 0.01). Multiple linear regression analysisshowed that resistin and FT3, FT4, and HOMA-IR was positively correlated, respeetively(r =0.756, P ＜ 0.01 ). Conclusion Resistin and FT3 and FT4 are related. Resistin might play important roles in insulin resistance and glucose and lipid metabolism disorders in patients with hyperthyriodism.

Significance of Galectin-3 and HBME-1 expression in differential diagnosis of thyroid nodules / 中国地方病学杂志

Objective To study the difference of galectin-3 and HBME-1 expression between benign and malignant thvreid nodules and to evaluate their clinical value.Methods Using immunohistochemical SP method,the paraffin-embedded tissues of 30 ewes papillary thyroid carcinoma(PTC)and 30 cases nodular goiter(NG) were examined to deteet the expression of Galectin-3 and HBME-1.Results The rates of positive staining of Galectin-3.HBME-1.Galectin-3 combined with HBME-1 in PTC were 93.3%(28/30),83.3%(25/30)and 100.0%(30/30),respectivdy,were higher than that of NG[20.0%(6/30),6.7%(2/30)and 26.7%(8/30)].There were significant differences between PTC and NG(X2＝32.85,35.65,34.74,all P＜0.01).The sensitivity,specificity,positive predietive value.negative predictive value and accuracy rate of using Galectin-3,HBME-1,Galectin-3 combined with HBME-1 in differentiation NG from FrIE were 93.3%,83.3%,100.0%;80.0%,93.3%,73.3%;82.3%,92.6%,78.9%:92.3%,84.8%,1 00%;86.7%,88.3%,86.7%,respectively.Conclusion Immunohistochemical stains of Galectin-3 and HBME-1 may be used as two lnarkel's for differentiating PTC and NG,it is especially sensitive when the two markers are jointly used.

Association of E23K polymorphism of inwardly rectifying K~+channel 6.2 gene with the phenotype of type 2 diabetes and glucose-lowering effect of gliclazide / 中华内分泌代谢杂志

The influences of E23K polymorphism of inwardly rectifying K~+channel 6.2 (Kir6.2) gene on the clinical phenotype of type 2 diabetes and glucose-lowering effect of gliclazide were investigated.The result showed that E23K polymorphism did not influence glucose-lowering effect of gliclazide,but serum creatinine level of patients with K/K genotype was higher than those of E/E and E/K genotypes (P