[The 507th case: hemolytic anemia, parvovirus B19, and multiple organ dysfunction].

A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.

[Effect of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients underwent haploidentical stem cell transplantation].

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

[Erythrocytosis after hematopoietic stem cell transplantation: report of 3 cases and literature review].

This is a report of three cases of three male patients. One of the patients had myelodysplastic syndrome, and two had aplastic anemia; their ages were 28, 32, and 21 years old, respectively. Two patients underwent sibling allogeneic hematopoietic stem cell transplantation, and one underwent haploidentical hematopoietic stem cell transplantation. All the patients showed elevated hemoglobin and hematocrit at 6, 16, and 9 months after transplantation, with normal white blood cells and platelets and no splenomegaly. All causes of secondary polycythemia were ruled out. Bone marrow morphology showed no erythroid hyperplasia. The PCR result for BCR-ABL (P210, P230, P190, and variants) was negative, and there were no mutations at the amino acid site 617 of JAK2, exon 12 of JAK2, exon 9 of CALR, and amino acid site 515 of MPL. All three patients had hypertension. One patient was treated with amlodipine, and the other two patients were treated with angiotensin receptor blockers. The durations of erythrocytosis for these three patients were 6 years and 3 months, 4 years and 7 months, and 5 years and 3 months, respectively through December 2022. There was no tendency for spontaneous remission. Erythrocytosis after hematopoietic stem cell transplantation is a rare complication. Previous reports in the literature suggest that the mechanism of post-transplant erythrocytosis in recipients of allogeneic hematopoietic stem cell transplantation may be different from that of recipients of other transplants.

[Clinical analysis of the efficacies of ganciclovir plus foscarnet and a single antiviral drug for the treatment of cytomegalovirus infection after haploidentical stem cell transplantation].

Objective: To evaluate and compare the efficacies of ganciclovir plus foscarnet and a single agent for the treatment of cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation. Methods: This study was a non-randomized clinical controlled trial. The data of patients who underwent haploidentical transplantation and developed CMV infection between January 1, 2021, and June 30, 2021, were retrospectively analyzed. Follow-up was conducted through telephone, inpatient consultations, and the review of outpatient medical records. The observed indicators included the incidence of CMV infection (including CMV disease), rate of recurrence of CMV infection, overall survival (OS), and disease-free survival (DFS). Results: A total of 242 patients were diagnosed with post-transplantation CMV infection; 116 patients tested positive for CMV DNA for more than 14 days (P=0.011). Of the 242 patients with CMV infection, 65 were treated with ganciclovir plus foscarnet, and 156 patients were treated with a single antiviral drug; the median durations of CMV seroconversion were 21 (3-60) and 14 (3-32) days for the combination and single-drug groups, respectively. There were no significant differences between their incidence of CMV infections and 1-year OS and DFS. Of the patients with refractory CMV infections, 53 (45.7%) were treated with ganciclovir plus foscarnet, and 63 (54.3%) were treated with a single antiviral agent. The median durations of CMV seroconversion for the combination and single-drug groups were 21 (15-60) days and 20 (15-45) days, respectively (P=0.472). Two patients in each group progressed to CMV disease (P=0.860). During follow-up, 12 patients (22.6%) in the combination group and 8 patients (12.7%) in the single-drug group experienced recurrent episode(s) of CMV infection (P=0.158). The 1-year OS of the combination and single-drug groups were 92.0% and 87.1%, respectively (P=0.543); the 1-year DFS were 90.3% and 85.7%, respectively (P=0.665). Univariate analysis revealed no associations between the antiviral agents used and OS and DFS (OS: HR=0.644, P=0.547; DFS: HR=0.757, P=0.666). Conclusions: There were no significant differences in the duration of CMV infection, incidence of CMV disease, rate of recurrence of CMV infection, and survival of the patients treated with the combination of antiviral drugs and a single antiviral drug.

[Safety and efficacy analysis of endovascular thrombectomy in patients with large vascular occlusion with low Alberta Stroke Program Early Computed Tomography Score].

Objective: To evaluate the safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT). Methods: Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT. Results: A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation (OR=4.478, 95%CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95%CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions: Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

[Clinical characteristics of patients with human adenovirus infection undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the clinical characteristics and prognosis of human adenovirus (HAdV) infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This is a retrospective case series study. Patients who received allo-HSCT and had symptoms of HAdV infection were tested in the Hematology Department at Perking University People's Hospital from August 2015 to October 2019. Real-time quantitative PCR was used to detect HAdV DNA from 2 728 patients with potential infection. HAdV DNA-positive patients were defined as having HAdV infection. The clinical features of these patients were analyzed, and a case-pair method was used to select patients without HAdV infection as the control group in a 1∶3 ratio. The clinical results of the two groups were compared using Kaplan-Meier and Log-rank testing. Results: A total of 7 119 samples were tested for HAdV, of which 99 samples from 36 patients were positive. Of these patients, 22 developed HAdV viremia, and 24 patients had concurrent infection with another virus. Nineteen patients had fever (53%), 25 had gastrointestinal symptoms (69%), 11 had respiratory symptoms (31%), nine had reduced liver function (25%), and six had nervous system symptoms (17%). Twenty-three patients developed acute graft-versus-host disease of grade 2 or higher. Of all the patients with HAdV infection, nine were treated with cidofovir, seven of whom became HAdV negative and two had invalid treatment. The median follow-up time was 496 (216, 940) d post-HSCT. The overall survival at 5 years post HSCT was 48.4%±9.2% vs. 91.3%±3.5% (χ2=65.03, P<0.001) in patients with and without HADV, respectively. The non-relapse mortality at 5 years post-HSCT was 40.8%±8.8% vs. 4.0%±2.0% (χ2=34.17, P<0.001) in patients with and without HADV, respectively. Conclusions: After allo-HSCT, HAdV-infected patients are dominated by gastrointestinal and respiratory symptoms and have an increased risk of combined acute graft-versus-host disease of >2 degrees. Patients with HAdV infection have poor overall survival and high non-relapse mortality.

[Prognostic analysis of patients with acute leukemia and central nervous system involvement undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mitigating the adverse prognosis associated with central nervous system leukemia (CNSL) and to assess the significance of prophylactic intrathecal injection. Methods: A retrospective cohort analysis was conducted involving 30 patients with acute leukemia who had a history of CNSL who underwent allo-HSCT at Peking University People's Hospital between September 2012 and March 2018 (referred to as the CNSL-positive group). In addition, 90 patients with acute leukemia were selected from the same period who underwent allo-HSCT without a history of CNSL (referred to as the CNSL-negative group) and a rigorous 1∶3 matching was performed based on disease type, disease status, and transplantation type to form the control group. The prognosis between the two groups was compared using Kaplan-Meier analysis and the high-risk factors for CNSL relapse post-transplant were identified through Cox proportional-hazards model. Results: The median age of patients in the CNSL-negative group was significantly higher than that of patients in the CNSL-positive group (32 years vs. 24 years, P=0.014). No significant differences were observed in baseline data, including sex, disease type, disease status at transplantation, donor-recipient relationship, and human leukocyte antigen consistency between the two groups. The median follow-up time was 568 days (range: 21-1 852 days). The 4-year cumulative incidence of relapse (71.4%±20.9% vs. 29.3%±11.5%, P=0.005) and the cumulative incidence of CNSL post-transplant (33.6%±9.2% vs. 1.2%±1.2%, P<0.001) were significantly higher in the CNSL-positive group than in the CNSL-negative group. Furthermore, the 4-year leukemia-free survival rate in the CNSL-positive group was significantly lower than that in the CNSL-negative group (23.1%±17.0% vs. 71.5%±11.6%, P<0.001). However, no significant differences were observed in the 4-year cumulative transplant-related mortality and overall survival rates between the two groups (both P>0.05). Multivariate analysis revealed that a history of CNSL before transplantation (HR=25.050, 95%CI 3.072-204.300, P=0.003) was identified as high-risk factors for CNSL relapse post-transplant. Conversely, haploidentical transplantation was associated with a reduced risk of CNSL relapse post-transplant (HR=0.260, 95%CI 0.073-0.900, P=0.034). Within the CNSL-positive group, seven patients received prophylactic intrathecal therapy after transplantation, and their CNSL relapse rate was significantly lower than that of the 23 patients who did not receive intrathecal therapy after transplantation (0/7 vs. 9/23, P=0.048). Conclusions: Patients with a history of CNSL have a higher risk of relapse and experience poorer leukemia-free survival following transplantation. The use of prophylactic intrathecal injection shows promise in mitigating CNSL relapse rates, although further validation through prospective studies is necessary to substantiate these observations.

[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation].

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.

[Clinical analysis of sirolimus as an alternative GVHD prophylaxis for patients with kidney injury undergoing allo-HSCT].

Objective: To explore the feasibility of sirolimus as an alternative graft versus host disease (GVHD) prophylaxis in patients with kidney injury after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective case series study. Medical records of 11 patients in Peking University People's Hospital from 1 August 2008 to 31 October 2022, who received sirolimus instead of cyclosporine to prevent GVHD, due to renal insufficiency after allo-HSCT, were analyzed retrospectively. Incidence of GVHD, infection, and transplant-associated thrombotic microangiopathy (TA-TMA), as well as renal function, were evaluated. Results: Among the 11 patients who received sirolimus, 6 were treated with haploidentical donor HSCT, and 5 were treated using matched sibling donor HSCT. The median (range) time of sirolimus administration was 30 (7-167) days after allo-HSCT, and the median (range) sirolimus course duration was 52 (9-120) days. During sirolimus treatment, 1 case did not undergo combined treatment with other prophylactic drugs, 3 cases received combined mycophenolate mofetil (MMF), and 1 case underwent combined CD25 monoclonal antibody treatment, while 6 cases had combined therapy with both MMF and CD25 monoclonal antibody. Of the 11 patients, 2 developed Grade Ⅲ acute GVHD, 1 developed severe pneumonia and died, and 1 developed TA-TMA, while nine patients had normal or improved renal function. Median (range) follow-up time was 130 (54-819) days. Non-relapse mortality was observed in 1 patient. Relapse mortality was also observed in 1 patient. Conclusion: Sirolimus-based alternative GVHD prophylaxis is a potentially viable option for patients undergoing allo-HSCT who cannot tolerate cyclosporine, but its efficacy and safety require further optimization and verification in prospective studies.

[Safety and survival analysis of haplo-identical hematopoietic stem cell transplantation in patients with severe aplastic anemia who had previous failure to antithymoglobulin treatment].

Objective: To investigate the safety and efficacy of haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) conditioning with the same dosage form of antithymoglobulin (ATG) in patients with severe aplastic anemia (SAA) failure to ATG. Methods: This was a retrospective cohort study. A total of 65 patients with SAA who failed ATG treatment and received haplo-HSCT conditioning with the same dosage of ATG at the Institute of Hematology, Peking University People's Hospital between July 2008 and October 2020 were included as the ATG treatment failure group. An additional 65 SAA patients who applied ATG for the first time during haplo-HSCT were randomly selected by stratified sampling as the first-line haplo-HSCT group. Baseline clinical data and follow-up data of the two groups were collected. Conditioning-related toxicity within 10 days after ATG application and long-term prognosis were analyzed. The Kaplan-Meier was used to calculate the overall survival rate, and the Log-rank test was applied to compare the rates of the two groups. Results: In the ATG treatment failure group, there were 36 males and 29 females, and the age at the time of transplantation [M (Q1, Q3)] was 16 (8, 25) years. In the first-line haplo-HSCT group, there were 35 males and 30 females, with a median age of 17 (7, 26) years. Within 10 days of ATG application, the incidence of noninfectious fever, noninfectious diarrhea, and liver injury in the ATG treatment failure group was 78% (51 cases), 45% (29 cases), and 28% (18 cases), respectively, and in the first-line haplo-HSCT group was 74% (48 cases), 54% (35 cases), and 25% (16 cases), respectively; the difference between the two groups was not statistically significant for any of these three parameters (all P>0.05). For graft-versus-host disease (GVHD), there was no significant difference between the ATG treatment failure group and the first-line haplo-HSCT group in the development of 100 day Ⅱ to Ⅳ acute GVHD (29.51%±0.35% vs. 25.42%±0.33%), Ⅲ to Ⅳ acute GVHD (6.56%±0.10% vs. 6.78%±0.11%), and 3-year chronic GVHD (26.73%±0.36% vs. 21.15%±0.30%) (all P>0.05). Three-year overall survival (79.6%±5.1% vs. 84.6%±4.5%) and 3-year failure-free survival (79.6%±5.1% vs. 81.5%±4.8%) were also comparable between these two groups (both P>0.05). Conclusions: Compared with no exposure to ATG before HSCT, similar early adverse effects and comparable survival outcomes were achieved in patients with SAA who failed previous ATG treatment and received haplo-HSCT conditioning with the same dosage form of ATG. This might indicate that previous failure of ATG treatment does not significantly impact the efficacy and safety of salvaging haplo-HSCT in patients with SAA.

[Application value of metagenomic next-generation sequencing for infectious pathogens in patients receiving allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the application value of Metagenomic Next-Generation sequencing (mNGS) in infectious patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: Patients suspected with local or systemic infections were retrospectively included after allo-HSCT in our department from April 2019 to November 2020. Pathogenic microorganisms were tested by mNGS in samples from peripheral blood, cerebrospinal fluid, alveolar lavage Liquid, abscess, etc. Other diagnostic methods such as bacterial/fungal culture, viral PCR detection were simultaneously explored comparing with mNGS results. Results: A total of 112 samples in 83 patients were detected by mNGS, and 34 pathogenic microorganisms were determined. Among these positive samples, 11 strains of bacteria (17 times) with the most common Escherichia coli (4/17) were reported. There were 7 strains of fungi (10 times) detected with primary Candida albicans (7/29). Although arvovirus 30.2% (39/129) were predominantly detected, its diagnostic relevance with infections was not definite. Other pathogenic viruses including cytomegalovirus (CMV) 25.6% (33/129) and Epstein Barr virus (EBV) 14.0% (18/129)were of significance. Comparing with golden diagnostic criteria, the sensitivity of mNGS was 86.5%, and specificity was 45.0%. Regarding single pathogen infection, the consistency of mNGS and conventional methods was 82.9% (29/35), while it was 16/17 in combination infections. Conclusion: mNGS could be a potential method to determine pathogens in patients suspected with infections after allo-HSCT.

[Relationship between treatment and prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ2 test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ2 test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.

[Analysis of clinical features of multiple myeloma with t(8;14)(q24;q32)].

Objective: To investigate the clinical manifestations and prognosis of multiple myeloma (MM) patients with t(8;14)(q24;q32). Methods: The clinical data of MM patients with G-banding results from 2004 to 2009 in Hematology Department of People's Hospital of Peking University were retrospectively analyzed. The general data, M protein related examination, cytogenetics data, therapeutic regimen and response evaluation of MM patients with t(8;14)(q24;q32) were collected. Results: Of all newly diagnosed multiple myeloma patients, the number of patients who had G-banding results was 940, among which 265 had abnormal karyotype in G-banding, accounting for 28.19%. The incidence of t(8;14)(q24;q32) detected by G-banding in MM patients was 0.85%(8/940), t(8;14)(q24;q32) accounted for 3.02%(8/265) of all choromosome abnormalities detected by G-banding. Seven of eight patients were male with a median age of 63.5(56-76) and the immunoglobulin sub-types seven in eight patients were lambda. All eight patients had DS stage Ⅲ at the time of initial diagnosis. FISH detection of these eight patients showed six patients(75%) with 1q21 amplification, and five patients(62.5%) with G-banding results showed abnormal chromosome 1. Among the eight patients, the number of patients reached complete response ,very good response and partial response were separately four, one and two, and the overall response rate(ORR) was 87.5%. After the median follow-up 35 months(23-65months), 2 patients died, and the OS of the dead patients exceeded 5 years. Conclusions: Patients with t(8;14)(q24;q32) accounted for 0.85% of the total who have the results of G banding in our hospital. Of our 8 patients, the light chain sub-type Lambda was more than Kappa, the patients were more common in males, accompanied by 1q21 amplification and chromosome 1 abnormality. The tumor load was high at the time of diagnosis, but the overall response to treatment was fair.

[Safety and efficacy evaluation of laparoscopic and open hepatectomy for hepatolithiasis: a propensity score matched analysis].

Objective: To compare the safety and efficacy of laparoscopic and open hepatectomy for hepatolithiasis. Methods: Between January 2014 and May 2020, the clinicopathological data of 254 patients with hepatolithiasis who underwent laparoscopic or open hepatectomy at the First Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College were collected retrospectively. There were 74 males and 180 females with age of (56±8) years (range: 38 to 77 years). Of the 254 patients, 162 underwent laparoscopic surgery (laparoscopic group) and 92 underwent open surgery (open group). Propensity score matching(PSM) was performed to match baseline characteristics of the two groups,and then the perioperative results and follow-up efficacy were compared between the two groups. The t-test, Mann-Whitney U test, χ2 test or Fisher's exact probability method was used to compare the perioperative data and follow-up results of the two groups after matching, respectively. Results: Each group had 63 patients after PSM with well-balanced baseline characteristics. There was no statistic difference in the type of hepatectomy,combined common bile duct exploration rate,T tube drainage placement rate,operation time,intraoperative transfusion rate,intraoperative accidental injury rate,initial and final stone clearance rate,and stone recurrence rate between the two groups. However,compared with the open hepatectomy group, the laparoscopic group had significantly lower intraoperative blood loss (M(IQR))(300(175)ml vs. 350(145)ml, Z=3.227,P=0.001),shorter postoperative hospital stay((10.6±4.1)days vs. (14.0±4.0)days,t=4.634,P<0.01),shorter time to postoperative oral intake ((1.8±1.1)days vs. (2.9±1.6)days, t=4.556, P<0.01), and lower postoperative complication rate (25.4%(16/63) vs. 49.2%(31/63), χ²=7.635, P=0.006). Conclusion: Laparoscopic hepatectomy is safe and effective for hepatolithiasis with the advantages of less intraoperative blood loss,lower postoperative complications and faster postoperative recovery.

Different subsets of haematopoietic cells and immune cells in bone marrow between young and older donors.

Young donors are reported to be associated with better transplant outcomes than older donors in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the mechanism is still unclear. The current study compared the different subsets of haematopoietic stem cells (HSCs) and their progenitors as well as immune cells in bone marrow (BM) between young and older donors. The frequencies of HSCs, multipotent progenitors (MPPs) and myeloid progenitors, including common myeloid progenitors (CMPs) and megakaryocyte-erythroid progenitors (MEPs), were decreased, whereas those of lymphoid progenitors, including multi-potent lymphoid progenitors (MLPs) and common lymphoid progenitors (CLPs), were increased in the BM of young donors compared with in that of older donors. Lower reactive oxygen species (ROS) levels were observed in BM HSCs and six progenitor lines in young donors. Furthermore, young donors demonstrated higher frequencies of naive T cells and immune suppressor cells, such as alternative macrophages (M2) and lower frequencies of memory T cells and immune effectors, including T helper-1 and T cytotoxic-1 cells, in BM than older donors. Multivariate analysis demonstrated that donor age was independently correlated with BM HSC frequency. Although further validation is required, our results suggest that the differences in the frequency and immune differentiation potential of HSCs in BM between young donors and older donors may partly explain the different outcomes of allo-HSCT.

[Comparison of EB virus infection between short term and long term use of mycophenolate mofetil for prophylaxis of graft versus host disease after haploidentical hematopoietic stem cell transplantation].

Objective: To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Method: Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF (n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF (n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result: Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P＞0.05). According to once, the incidence of EBV viremia, defined as EBV＞103 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively (P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [HR=1.022(95%CI 1.006-1.038),1.600(95%CI 1.059-2.418);P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)(P=0.005) and 10.1% (20/199) versus 8.0% (24/299) (P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [HR=1.908(95%CI 1.079-3.373),1.752(95%CI 1.161-2.643);P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P＞0.05) between the two groups. Conclusion: Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.

[Daratumumab for the treatment of primary systemic amyloidosis: a multicenter retrospective analysis].

Objective: To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis. Methods: Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed. Results: All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients. Conclusion: Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

[Prognostic significance of DEK-NUP214 fusion gene in patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People's Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test. Results: The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome. Conclusion: Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.

[Negative effects of donor specific anti-HLA antibody on poor hematopoietic recovery in patients with hematological diseases receiving haploidentical stem cell transplantation and rituximab for desensitization].

Objective: To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization. Methods: Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results: There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR (HR=6.101, P=0.021). PHR was associated with higher NRM (HR=4.110, P=0.026), lower DFS (HR=3.656, P=0.019) and OS (HR=3.656, P=0.019). Conclusion: Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.

[The effect of donor cytomegalovirus serological status on the outcome of allogeneic stem cell transplantation].

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.