Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.

Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.

Objective:To compare the efficacy of haplotype hematopoietic stem cell transplantation (HIDT) and sibling matched hematopoietic stem cell transplantation (MSDT) in the treatment of complete remission (CR) acute T-lymphoblastic leukemia (T-ALL) .Methods:We retrospectively analyzed the clinical characteristics and outcomes of 98 patients who underwent HSCT in Hebei Yanda Ludaopei hospital with HID ( n=81) or ISD ( n=17) between May 2012 and May 2016. Results:The incidence of grades 2-4 and 3-4 acute-versus-host disease 100 days after HSCT were 51.9% (95% Confidence interval [ CI] 42.0%-64.0%) vs 29.4% (95% CI 14.1%-61.4%) ( P=0.072) and 9.8% (95% CI 5.1%-19.1%) vs 11.8% (95% CI 3.2%-43.3%) ( P=1.000) for HIDT and MSDT. The 100-day cumulative incidences of CMV and EBV viremia were 53.1% (95% CI 43.3%-65.2%) vs 29.4% (95% CI 14.1%-61.4%) ( P=0.115) and 35.8% (95% CI 26.8%-47.9%) vs11.8% (95% CI 3.2%-43.3%) ( P=0.048) . The 5-year overall survival, leukemia-free survival, cumulative incidences of relapse, and no-relapse mortality were 60.5% (95% CI 5.4%-49.0%) vs 68.8% (95% CI 11.8%-40.0%) ( P=0.315) , 58.0% (95% CI 5.5%-46.5%) vs 68.8% (95% CI 11.8%-40.0%) ( P=0.258) , 16.1% (95% CI 9.8%-26.4%) vs 11.8% (95% CI 3.2%-43.3%) ( P=0.643) , 25.9% (95% CI 17.9%-37.5%) vs 19.4% (95% CI 6.9%-54.4%) ( P=0.386) for HIDT and MSDT, respectively. Conclusion:HID could be a valid alternative donor for patients with T-ALL in CR lacking an identical donor.

Objective:To study the clinical efficacy of chimeric antigen receptor T-cell (CART) treatment followed by a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with B-cell acute lymphoblastic leukemia (ALL) who relapsed following the first HSCT.Methods:Retrospective analysis of the clinical characteristics and prognosis of 41 patients with B-cell ALL who received a second allo-HSCT from October 2015 to June 2020 in Hebei Yanda Lu Daopei Hospital. After the first HSCT, all patients received CD19-CART, or CD22-CART treatment following a relapse of bone marrow morphology or extramedullary leukemia.Results:A total of 41 patients (male, 21; female, 20) were included in this study. The median age at the second HSCT was 16 (3-46) years. There were 31 cases of bone marrow recurrence (75.6%) , 5 cases of extramedullary recurrence (12.2%) , and 5 cases of bone marrow and extramedullary recurrences (12.2%) . After relapse, 35 patients (85.4%) received CD19-CART treatment, 2 patients received CD22-CART treatment (4.9%) , and 4 patients received CD19-CART and CD22-CART treatments (9.8%) . The expected 3-year overall survival (OS) , leukemia-free survival, cumulative relapse incidence, and non-relapse mortality (NRM) of patients after the second HSCT were 48.9% (95% CI 23.0%-70.6%) , 41.8% (95% CI 17.3%-64.9%) , 8.8% (95% CI 2.9%-26.4%) , and 51.1% (95% CI 31.2%-83.6%) , respectively. The 1-year OS of patients who relapsed ≤6 months and >6 months after the first HSCT were 45.0% (95% CI 12.7%-73.5%) and 75.0% (95% CI 51.4% -88.8%) ( P=0.017) , respectively. Conclusion:CART bridging in the second HSCT enables some B-cell ALL patients who relapsed after the first HSCT to achieve long-term survival. However, because of the high NRM, further modifications could help improve the outcome.

Objective:To study the clinical results and prognostic factors for allo-HSCT of Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL) in complete remission (CR) in the era of tyrosine kinase inhibitors (TKI) . Methods:We performed a retrospective analysis of the clinical characteristics of 116 patients with Ph +ALL who underwent allo-HSCT while in CR. Results:The study population included 72 men and 44 women. The median patient age was 20 years (4-64 years) . The patients received sibling-identical donor ( n=21) , haplo ( n=77) , and unrelated donor ( n=18) HSCT. The overall survival (OS) rate at 5 years was 73.2% (95% CI 63.8% -80.5% ) . In particular, the 5-year OS can reach 87.5% when the time from diagnosis to transplant is <180 days. The 5-years DFS was 61.4% (95% CI 51.8% -69.7% ) , the 5-year molecular and morphology cumulative relapse incidence was 18.5% (95% CI 12.6% -27.3% ) , and the 5-year TRM was 19.9% (95% CI 13.8% -28.7% ) . A multivariate analysis showed that an age range of 15-39 years ( HR=2.730, P=0.044) , time from diagnosis to HSCT ≥ 180 days ( HR=4.534, P=0.010) , and Ⅲ-Ⅳgrade aGVHD ( HR=7.558, P=0.000) were significantly associated with an inferior overall survival. Limited cGVHD subgroup had better OS ( HR=0.300, P=0.034) . Sex, WBC count at diagnosis, type of BCR-ABL fusion genes, somatic gene mutations, CR 1 or >CR 1, MRD negative or positive, conditioning regimen based on TBI or Bu, conditioning intensity, donor source, GVHD prophylactic proposal using cyclosporine or tacrolimus, presence/absence of CMV viremia, and presence/absence of EBV viremia were not significantly different in terms of the OS and DFS. Conclusion:Factors influencing the overall survival of Ph + ALL patients who underwent allo-HSCT in CR in the TKI era include age, time form diagnosis to HSCT, and aGVHD severity.

Objective:To evaluate the association of TP53 mutations with the clinical outcomes of Ph-negative B-ALL following allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Total 300 patients with Ph-negative B-ALL who underwent allo-HSCT at the Hebei Yanda Ludaopei Hospital from May 2012 to May 2017 were retrospectively analyzed; their clinical characteristics, TP53 gene mutation type, and association between TP53 mutations and transplantation outcomes, including leukemia-free survival (LFS) , overall survival (OS) , non-relapse mortality (NRM) , relapse, and GVHD, were evaluated.Results:Total 23 patients had TP53 mutations; all the TP53 mutations affected P53’DNA-binding domain. The 5-year-LFS, OS, and RI were 34.8% and 62.3% ( P=0.001) , 41.9% and 65.1% ( P=0.020) , and 47.8% and 14.8% ( P=0.000) , respectively, for TP53 mutations and wild-type TP53 patients. However, there were no significant differences in NRM and GVHD. Multivariate analysis showed that TP53 mutations remained adverse prognostic factors for LFS, OS, and RI after allo-HSCT. Conclusion:Some patients with TP53 mutations can achieve long-term survival with allo-HSCT. TP53 mutations are adverse prognostic factors for Ph-negative B-ALL patients who undergo allo-HSCT.

Objective To analyze the correlation between vitamin D levels and vascular endothelial function and plasma renin activity (PRA) in hypertensive patients.Methods 415 patients with essential hypertension admitted to our hospital from January 1 to December 2017 were selected as the experimental group.142 healthy subjects who received physical examination and met the included indicators were selected as the control group.The blood biochemical indexes and the 25 (OH) D contents in the blood of two groups were detected and analyzed.The experimental group was divided into vitamin D mild deficiency group (15-30 mmol/L),severe deficiency group [25 (OH) D ＜ 15 mmol/L] and normal group [25 (OH)D ＞ 30 mmol/L] according to vitamin D content.The endothelial function (RHI value) and renin were compared in the three groups,and multiple linear regression analysis was performed on endothelial function and orthotopic renin activity and related factors.Results The diastolic blood pressure,vitamin D content and blood lipid biochemical indexes of the experimental group and the control group were significantly different (P ＞ 0.05).The higher the vitamin D content,the lower the plasma renin activity PRA;the RHI value of the vitamin D severe deficiency group was lower than the vitamin D normal group [(1.4 ±0.15)mmol/L vs (1.6 ± 0.20) mmol/L] (P ＜ 0.05).Vitamin D was negatively correlated with 24 hours systolic blood pressure (24 h SSD),the standard deviation of 24 hours diastolic blood pressure (24 h DSD),the Standard deviation of daytime systolic blood pressure (dSSD),the Standard deviation of daytime diastolic blood pressure (dDSD),the Standard deviation of nighttime systolic blood pressure (nSSD),the Standard deviation of nighttime diastolic blood pressure (nDSD) (P ＜ 0.05),and positively correlated with the decrease of night systolic blood pressure and night diastolic blood pressure.Vitamin D and total cholesterol were independent influencing factors of endothelial function (P ＜ 0.01).Vitamin D and 24 h mean heart rate were independent influencing factors of orthostatic renin activity (P ＜ 0.01).Conclusions The low vitamin D content in patients with essential hypertension affects endothelial function and plasma renin activity,which should be paid more attention in clinical practice.

Objective: To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis of 258 patients with AML in CR (186 cases in CR₁, 72 cases in CR₂) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk. Results: ①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34⁺ cell number and transfused CD3⁺ cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR₂ compared to that in CR₁ (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM. Conclusion Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR₁ and CR₂ patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR₁-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR₁-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR₁-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: ①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR₁-AML. Conclusion MRD positive pre-conditioning was the only negative impact factor for patients with CR₁-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR₁-AML after allo-HSCT.