Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Objective:To look into the security of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) using rabbit anti-human thymocyte immunoglobulin (rATG) .Methods:Twenty-seven patients who used rATG in the first and second allo-HSCT at the Institute of Hematology, Peking University were enrolled in the study. Experienced toxicities associated with the conditioning protocol within 10 days (-5 d to +3 d) following the beginning of the rATG application, including fever, diarrhea, arrhythmia, reduced blood pressure, liver damage, seizures, and other problems.Results:The overall incidence of conditioning regimen early adverse reactions during the first transplantation and the second allo-HSCT conditioning regimen was 96.3% and 77.8% ( P=0.043) . Fever rates were 81.5% and 63.0% ( P=0.129) , diarrhea rates were 59.3% and 25.9% ( P=0.013) , liver damage rates were 22.2% and 25.9% ( P=0.75) , and the rates of other events (cardiac arrhythmia, low blood pressure, and epilepsy) were 3.7% and 18.5% ( P=0.083) . Adverse reactions that occurred during both the first and second course of rATG applications have been improved with symptomatic treatment, and no treatment interruptions occurred. Conclusion:Reusing rATG in a second transplant was risk-free and did not result in higher early toxicities.

Objective:To explore the relationship between anti-human leukocyte antigen (HLA) antibodies and transplant outcomes in patients with hematological diseases who underwent matched sibling donor transplantation (MSDT).Methods:A retrospective analysis was conducted in 168 patients with hematological diseases who received MSDT in Peking University People's Hospital from March 2015 to November 2017. All patients received detection of anti-HLA antibodies before transplantation, and the correlation between anti-HLA antibodies and transplant outcomes such as hematopoietic cells implantation, blood product transfusion and prognosis after transplantation were analyzed.Results:Among the 168 patients, 28 (16.7%) were positive for anti-HLA class Ⅰ or class Ⅱ antibodies, and 14 (8.3%) were positive for both anti-HLA class Ⅰ and class Ⅱ antibodies. All patients received neutrophil engraftment, 164 patients (97.9%) received platelet engraftment. Univariate analysis showed that there were no effects of anti-HLA antibodies on neutrophil engraftment and engraftment time, platelet engraftment and engraftment time, the volume of red cell transfusion, the volume of platelet transfusion, overall survival (OS) rate, disease free survival (DFS) rate and transplant-related mortality (TRM) in patients with hematological diseases underwent MSDT (all P > 0.05). Multivariate analysis showed that platelet engraftment was associated with better OS ( HR=0.065, 95% CI 0.017-0.252, P < 0.01), better DFS ( HR=0.083, 95% CI 0.024-0.289, P < 0.01) and lower TRM ( HR=0.094, 95% CI 0.014-0.626, P=0.015). Conclusion:Anti-HLA antibodies have no effect on transplant outcomes of patients with hematological diseases who have received MSDT.

Objective: To investigate the association of hematological complete remssion (HCR) status on the outcomes of the patients with B-cell acute lymphoblastic leukemia (B-ALL) who were undergoing haploidentical stem cell transplantation (Haplo-SCT). Methods: Retrospective analysis was performed on 317 patients with B-ALL who received Haplo-SCT with HCR before transplantation in the Institute of Hematology, Peking University from September 2012 to June 2016. A Cox proportional hazards model was used to analyze the effects of HCR status before transplantation on the outcomes of Haplo-SCT. Results: The 3-year cumulative incidences of non-relapse mortality (NRM) and cumulative incidence of relapse (CIR) were 15% and 15%, respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 71% and 74%, respectively. There was no statistical difference for 3-year NRM, CIR and LFS among the HCR patients with recovery of absolute neutrophil count (ANC) and platelet (CR) group, without recovery of ANC and with or without recovery of platelet (CRi) group and those in HCR with recovery of ANC but without recovery of platelet (CRp) group (P value ＞0.05 for all). The probability of OS in cases of CR group was significantly higher than that of CRi group (76% vs 59%，P=0.049). Multivariate analysis showed that factors associated with CIR included pre-transplantation minimal residual disease (P=0.006) and chronic GVHD (P=0.020). Platelet engraftment was associated with NRM, LFS, and OS (P＜0.001 for all). Grades Ⅲ-Ⅳ GVHD was associated with NRM (P＜0.001) and OS (P=0.035). Chronic GVHD was correlated with LFS (P＜0.001). Conclusion Our results indicate that no effect of HCR status before transplant on the outcomes was observed in patients with B-ALL who underwent Haplo-SCT.

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)%, χ²=0.274, P=0.600], non-relapse mortality[NRM, (14.0±4.3)% vs (9.0±6.3)%, χ²=0.913, P=0.339], leukemia-free survival[LFS, (75.0±5.1)% vs (75.0±8.3)%, χ²=0.256, P=0.613], and overall survial [OS, (77.0±5.2)% vs (80.0±8.1)%, χ²=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) %, χ²=32.687, P<0.001], better 4-year LFS [(76.2±4.7)% vs (32.8±8.7)%, χ²=26.234, P<0.001] and OS[(79.0±4.7)% vs (39.0±9.1)%, χ²=25.253, P<0.001], and comparable NRM[(12.5±4.1)% vs (12.0±7.1)%, χ²=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.

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1⁺/FLT3-ITD^- increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

Objective To evaluate the levels of total serum bilirubin(TSB),amplitude integrated electroencephalogram(aEEG) monitoring and brainstem auditory evoked potential(BAEP) individually and in combination for the early diagnosis of neonatal acute bilirubin encephalopathy by receiver operating charac-teristic( ROC) curve. Methods Clinical data was retrospectively analyzed. A total of 152 infants were diag-nosed with hyperbilirubinemia,including 119 cases of non-bilirubin encephalopathy group and 33 cases of bil-irubin encephalopathy group. The detection results of peak serum bilirubin,aEEG,BAEP combined with the three methods were determined with ROC curve analysis. Results The areas under ROC curve of TSB lev-el,aEEG,BAEP and in combination were 0. 900,0. 738,0. 767,0. 925,respectively,the corresponding sensi-tivity(specificity) in the cut-off point were 90. 91%(78. 15%),87. 88%(59. 66%),65. 52%(87. 91%), 93. 10%(82. 42%),respectively. It showed that the area under ROC curve of the maximum,the comprehen-sive assessment in diagnostic sensitivity and specificity of the combination of three methods were better than any single detection method by ROC curve. Conclusion The methods of TSB level,aEEG and BAEP play an important role in the diagnosis of neonatal bilirubin encephalopathy,and combination with the three meth-ods can improve the accuracy of diagnosis.

Objective To study the risk factors and prognosis of very/extremely low birth weight preterm (VLBW/ELBW) infants with bronchopulmonary dysplasia (BPD) during the first three years of life.Method From January 1st to December 31st,2012,a retrospective study was conducted on the VLBW/ELBW preterm infants with ＞ 28 days of hospitalization in the NICU of our hospital.The infants were assigned into BPD group (FiO2 ＞ 21％) and non-BPD group depending on the oxygen requirement on the 28th day after birth.The incidences of bronchitis,pneumonia,wheezing and re-hospitalization during the first three years of life were analyzed.The pulmonary function tests were performed at one-year-age.Independent-sapmles t test,Kruskal-wallis test and x2 test were used to compare the results between the two groups.Result A total of 72 patients were enrolled into this study.34 patients in the BPD group and 38 in the non-BPD group.The gestational age,birth weight and the use of INSURE technique of BPD group were significantly lower than non-BPD group,while the duration of hospital stays were longer than non-BPD group (P ＜0.05).The ratio of male,neonatal respiratory distress syndrome (RDS),patent ductus arteriosus (PDA),intrauterine infection,mechanical ventilation,nosocomial infection and the inhalation of high concentrations of oxygen were significantly higher in BPD group than non-BPD group (P ＜ 0.05).Incidences of bronchitis and wheezing during 0 ～ 1,1 ～ 2 and 2 ～ 3 years of age in the BPD were significantly higher than non-BPD group,separately.No significant differences existed in the incidences of pneumonia and re-hospitalization between the two groups.Pulmonary function test showed that the respiratory rate (RR) and peak tidal expiratory flow in the BPD group were significantly higher than non-BPD group,while the tidal volume,peak expiratory time and peak expiratory volume were significantly lower in BPD group than non-BPD group (P ＜ 0.05).Conclusion BPD often occurs in preterm infants with gestational age less than 32 weeks.It may cause impaired pulmonary function,characterized by obstruction in small airway,and increases the risk of bronchitis and wheezing during the first three year of life.

Objective: To analyze the clinical value of real-time PCR for virus detection in the diagnosis and treatment of patients after allo-HSCT who had no infection evidence of pneumonia using routine pathogen detection panel. Methods: The clinical data of 71 episodes with acute lung injury from May 2015 to March 2017 after allo-HSCT in hematology department of Peking University People’s Hospital (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF) samples. Results: Among 71 episodes with acute lung injury, a total of 15 patients were diagnosed as lower respiratory tract disease merely associated with virus (detection rate of 21.13%) , 19 episodes were absent of lower respiratory tract infection. The median time from allo-HSCT to the occurrence of lung injury were 176 (49-1 376) d and 196 (57-457) d respectively (z=-0.191, P=0.864) . There were no statistical differences for baseline characteristics and clinical features between two groups. The 100-day attributable mortalities were 13.3% (2/15) and 26.3% (5/19) (χ²=0.864, P=0.426) . Patients with low-dose steroids treatment had favorable outcome than those with high-dose steroids treatment (the dose of methylprednisolone ≥250 mg/d as standard) [4.2% (1/24) vs 60.0% (6/10) ]. In patients with detectable virus in BALF, 2 patients died with early high-dose steroids treatment, while 11 patients survived with no steroids treatment or late application. Conclusions Virus infection should be considered in post-HSCT pneumonia patient with negative result using routine pathogen detection panel. Expanding virus detection panel by PCR in BALF could increase diagnostic precision and might be instructive to treatment.

Objective: To compare incidence and clinical features of hemorrhage cystitis (HC) after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (HSCT) and matched sibling donor (MSD) HSCT. Methods: Medical records of 609 (including 406 HID-HSCT and 203 MSD-HSCT cases) hematologic malignancies patients treated with HSCT undergoing myeloablative conditioning regimen from January 2011 to December 2012 were analyzed retrospectively. Results: HC occurred 183 in HID and 17 ones in MSD respectively. The cumulative incidence of HC in HID group was higher than in MSD group[ (45.6±2.5) % vs (8.5±2.0) %, χ²=77.331, P<0.001], and the cumulative incidence of severe HC (grade 3-4) in HID cases was also higher than in MSD ones[ (11.2±1.9) % vs (2.1±1.1) %, χ²=12.883, P<0.001]. All HCs were occurred within 180 days in both groups. The median time to onset in two groups were 27 days after HSCT (range 0-177 days) and 29 days after HSCT (range 6-72 days) respectively (P=0.766) . The median duration of HC in two groups were 21 days (range 3-157 days) and 13 days (range 5-67 days) , respectively (P=0.182) . The total efficiency of treatment in two groups were 69.9% and 70.6% respectively (χ²=0.003, P=1.000) . Conclusion The cumulative incidences of HC and severe HC were higher in HID cases than in MSD ones. The median time to onset and median duration of HC and therapeutic outcome between HID and MSD were comparable.