[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.

[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.

[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.

[Comparison of air filled anterior approach of sternocleidomastoid muscle and space of sternocleidomastoid muscle for treatment of thyroid papillary carcinoma under axillary endoscope].

Objective: To evaluate the application of the anterior sternocleidomastoid muscle approach in transaxillary endoscopic thyroidectomy. Methods: The clinical data of 180 patients undergoing transaxillary endoscopic thyroidectomy for thyroid cancer in the Department of General Surgery of the Affiliated Hospital of Nantong University from March 2021 to March 2023 were retrospectively analyzed. There were 27 males and 153 females, aged (37.5±8.0)years, range: 27 to 52 years. The anterior approach of sternocleidomastoid muscle was used in 100 cases, and the interspace approach of sternocleidomastoid muscle was used in 80 cases between the two groups. The postoperative efficacy, complications and satisfaction of the two groups were compared. Results: There was no difference between the two groups in the number of lymph node dissection (using nano carbon tracer), hospital stay, and postoperative complications (transient decrease in parathyroid function, laryngeal nerve injury) (P>0.05). The anterior approach of sternocleidomastoid muscle had shorter cavity building time[(17.8±2.9)vs(20.1±3.7) min], less drainage volume the second day after operation[(18.7±5.2)vs(23.5±6.3) ml], and less discomfort in the neck (P<0.05). Conclusion: The anterior approach of sternocleidomastoid muscle under complete transaxillary endoscopy has certain advantages in the time of cavity construction, the drainage volume the second day after the operation, and the reduction of cervical discomfort after the operation. The operation is safe and reliable.

[A single-center retrospective analysis of 100 consecutive cases treated with lenalidomide/bortezomib/dexamethasone in newly diagnosed multiple myeloma].

Objective: To investigate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (RVD) in patients with newly diagnosed multiple myeloma (NDMM). Methods: A total of 100 consecutive NDMM patients treated with RVD from August 2016 to September 2020 at Peking University People's Hospital were retrospectively analyzed, including response, drug toxicity, follow-up and survival, and subgroup analysis. Results: The median follow-up time was 19.5 (2.0-57.0) months. For patients undergoing autologous stem cell transplantation (ASCT) after RVD regimen, the objective response rate (ORR)/complete response+stringent complete response (CR+sCR)/≥very good partial response (VGPR) rates were 100%, 73.3% (33/45), 95.6% (43/45) respectively. For 54 patients not receiving transplantation, the ORR/CR+sCR/≥VGPR rates were 79.6% (43/54), 18.5% (10/54), 51.9% (28/54) respectively. As to the survival analysis, 2-year progression free survival (PFS) rates were 84.5% and 70.9% in transplant and non-transplant patients respectively (P=0.102). Two-year overall survival (OS) rates were 100% and 80.8% in transplant and non-transplant patients respectively (P=0.003). The common hematologic adverse events (AEs) were thrombocytopenia (33%) and neutropenia (25%). Abnormal liver function (43%) and peripheral neuropathy (24%) were recognized more as non-hematologic AEs. Conclusion: RVD as front-line regimen has high efficient response rate and acceptable safety in Chinese NDMM patients.

[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.

[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.

[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.

[Analysis of the effects of esophageal cancer screening in Henan rural areas with cancer screening program, 2014-2018].

Objective: To analyze the effects of esophageal cancer screening in Henan rural areas with cancer screening program from 2014 to 2018. Methods: From July 2014 to June 2019, according to the National Early Diagnosis and Treatment of Upper Gastrointestinal Cancer in Rural Areas Project, cluster sampling method was adopted in 16 counties/county-level cities in rural areas with high incidence of esophageal cancer in Henan province. Endoscopic iodine staining and indicative biopsy were used to screen esophageal cancer. The patients with mild and moderate dysplasia confirmed in screening were followed up. The distribution of esophageal diseases in the screening population was calculated, and Chi-square test was used to compare the differences of detection rate and early diagnosis rate between the primary screening population and the follow-up population. Results: The age of 116 630 primary screening population was (54.29±7.70) years old, and the proportion of males was 41.2% (48 108). In the primary screening population, patients with normal esophagus, mild to moderate dysplasia, severe dysplasia and above accounted for 92.91% (108 363), 6.03% (7 035) and 1.06% (1 232), respectively. The detection rate of esophageal cancer was 1.06% (1 232/116 630), and the rate of early diagnosis was 85.80% (1 057). Among the follow-up population of 6 154 people, those with normal esophagus, mild to moderate dysplasia, severe dysplasia and above diseases accounted for 63.45% (3 905), 33.13% (1 519) and 3.41% (210), respectively. The detection rate of esophageal cancer was 3.41% (210/6 154), and the rate of early diagnosis was 91.90% (1 939). Compared with the primary screening population, the risk of esophageal cancer was higher in the overall follow-up population, people either with mild or with moderate dysplasia diagnosed in primary screening, with OR values (95%CI) of 3.23 (2.78, 3.75), 1.85 (1.49, 2.29) and 8.13 (6.69, 9.88), respectively. Conclusion: From 2014 to 2018, in the early diagnosis and early treatment of upper digestive tract cancer project in rural areas of Henan Province, the detection rate of the follow-up population is significantly higher than that of the primary screening population. Improving follow-up rate and paying more attention to the screening of people who need follow-up could further improve the screening effect.

[The clinical characteristics of patients with primary plasma cell leukemia and the efficacy of novel agents and hematopoietic stem cell transplantation].

Objective: To analyze the immunophenotype and cytogenetic characteristics of primary plasma cell leukemia (pPCL), and to evaluate the efficacy of bortezomib and hematopoietic stem cell transplantation as main treatment. Methods: A retrospective cohort study was conducted including 42 pPCL patients admitted to Peking University People's Hospital from January 1998 to March 2019. All patients were followed up until December 31, 2019. The immunophenotype and cytogenetic characteristics were compared with historical data of multiple myeloma (MM). Thirty-nine patients were divided into bortezomib-based group (29 cases) and non-bortezomib group (10 cases). All patients were also divided into hematopoietic stem cell transplantation (HSCT) group (15 cases) and non-HSCT group (24 cases).Chi-square test was used for efficacy comparison, and Kaplan-Meier method was used for univariate prognostic analysis. Cox proportional hazards model was used for multi-variant analysis. Results: pPCL accounted for 2.6% of the total patients with plasma cell diseases during the same period. There were 22 males and 20 females, with a median age of 50 (30-77) years old at diagnosis. In immunophenotype analysis, tumor cells in pPCL patients also expressed CD38, CD138, CD45, which was similar as patients with MM. However the expression of CXCR4 were more frequently seen in pPCL(73.1% vs. 34.7%, P= 0.000), while intensity of CD9 and CD200 was lower (40.7% vs. 62.5%, P =0.028, 33.3% vs. 58.0%, P=0.021).Overall response rate of bortezomib-based therapy was superior to non-bortezomib therapy (69.0% vs.50.0%). The median survival was 18.2 (0.2-95.7)months, and the 1-and 2-year survival rates were 61.9% and 37.4%, respectively. Multivariate prognostic analysis suggested that age (P= 0.027) and efficacy(P= 0.035)were significantly correlated with survival.HSCT resulted in superior survival compared with chemotherapy alone(26.8 vs. 8.1 months, P=0.021). Conclusions: Immunophenotypes and cytogenetic abnormalities in patients with pPCL are different from those with multiple myeloma. Bortezomib based regimens improve response rate and survival of pPCL. Hematopoietic stem cell transplantation also predicts survival benefits.

[The efficacy and safety of daratumumab in relapsed and refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM). Methods: The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People's Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019. Results: Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab. Conclusion: Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

[Surgical treatment of severe, refractory hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: a report of 17 patients].

Objective: To investigate the clinical effect and safety of surgical treatment for severe, refractory hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Patients with severe HC, who were admitted to Peking University Institute of Hematology from January 2010 to December 2015, were enrolled in this study.All patients were refractory to medical managements and received bladder surgery including mucous electrocoagulation and/or selective transcatheter arterial embolization. Results: A total of 17 patients with severe HC (grade Ⅲ, n=5; grade Ⅳ, n=12) received surgical treatment, including 11 embolization and 18 mucous electrocoagulation.The median time from allo-HSCT to surgery was 107 d (46-179 d) and 75 d after HC.Eight patients only received embolization.Four patients only received mucous electrocoagulation.Five patients were given combined embolization and electrocoagulation.HC was cured in 11 patients, improved in 1 patient, which corresponded to a response rate of 70.6% and complete remission rate of 64.7%.Five patients didn't respond to these methods.In patients with response, macroscopic hematuria disappeared 3 to 10 days after treatments whereas microscopic hematuria vanished after 25 to 32 days.Both procedures were well tolerated and no severe adverse effects were observed. Conclusion: Surgery of bladder mucous electrocoagulation and/or selective arterial embolization are safe and effective for severe HC.

[Analysis of risk factors related to the prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the prognostic factors of late-onset severe pneumonia (LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From January 2009 to December 2015, 68 patients with LOSP after allo-HSCT at Peking University Institute of Hematology were enrolled. In this retrospective study, univariate and multivariate analysis were used to evaluate the prognostic factors for LOSP after allo-HSCT. Results: The median time from allo-HSCT to the development of LOSP was 213 (90-2 330) days. The overall survival rate was 42.6% (29/68). The median survival time from LOSP to death was 21 days. Early mortality was defined as death within 21 days after LOSP, as late death more than or equal to 21 days. The median oxygenation index was 199.15 (92.21-290.48) mmHg. LOSPs in thirty-two patients (36.8%) were caused by virus, bacteria, fungi or mixed pathogens. The median C-reactive protein (CRP) was 75.65 (0.94-451.00) mg/L. The median procalcitonin (PCT) was 0.66 (0.00-249.00) µg/L. The higher PCT value indicated an early higher mortality rate by the ROC curve (PCT: cut-off ≥0.94 µg/L). Furthermore, multivariate analysis suggested that PCT more than or equal to 0.94 µg/L was a risk factor for early death of LOSP (OR=5.77, 95%CI 1.66-20.11, P=0.006). LOSP occurred later or equal to 213 days after allo-HSCT was also a risk factor of early death in LOSP (OR=4.74, 95%CI 1.33-16.89, P=0.017). No previous history of chronic graft versus host disease (GVHD) (OR=4.50, 95%CI 1.58-12.83, P=0.005) and LOSP later or equal to 213 days (OR=4.40, 95%CI 1.61-11.99, P=0.004) were the risk factors of late death in LOSP. Conclusions: PCT more than or equal to 0.94 µg/L and LOSP later or equal to 213 days are the risk factors of early death in LOSP. No previous chronic GVHD and LOSP later or equal to 213 days are the risk factors of late death in LOSP.

CTLA-4 polymorphisms and haplotype correlate with survival in ALL after allogeneic stem cell transplantation from related HLA-haplotype-mismatched donor.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been established as an effective treatment for patients with hematological malignancies. Disease relapse remains a major cause of transplant failure. T cell homeostasis is critical to determine the potency of the GVT effect. Recent studies have shown the association of the CTLA-4 polymorphisms with the outcome after HLA-identical sibling allogeneic HSCT. METHODS: In this study, we focused on four CTLA-4 polymorphisms, and analyzed the impact of donor genotypes and haplotypes on the conditions of 152 acute leukemia patients (ALL 83) after related HLA-haplotype- mismatched transplantation. The four SNP genotypes (-1661, -318, CT60 and +49) were determined by TaqMan SNP genotyping assays. RESULTS: ALL recipients of donors with +49 GG showed significantly lower OS (67.7 vs. 90.3 %, P = 0.015) than those with GA+AA. Multivariate analyses showed that +49 GG was an independent risk factor for OS (HR: 0.306, 95 % CI 0.111-0.842, P = 0.022) .23 ALL patients receiving mDLI showed significantly lower OS with +49 GG donor than those with GA+AA (30.0 vs. 83.1 %, P = 0.003). The haplotype analysis revealed only three haplotypes in the donor population -1661/-318/CT60/+49 i.e., ACGG, ACAA and GTGA, the frequencies were 64.1, 19.4 and 16.5 %, respectively. Donors with and without the ACGG/ACGG haplotype had the same effect on transplant outcomes as those with +49 GG and +49 GA+AA. CONCLUSION: In summary, the CTLA-4 +49 GG and the haplotype ACGG/ACGG reduced the overall survival in ALL after allo-HSCT from the related HLA-haplotype-mismatched donor, knowledge of the CTLA-4 polymorphism and haplotype may provide useful information for donor selection and individual application of immunosuppressive agents and immunotherapy.

Late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation: prognostic factors and treatments.

BACKGROUND: In this study, we aimed to evaluate the prognostic factors associated with and treatments for late-onset severe pneumonia (LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Fifty consecutive patients who underwent non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and met the criterion of LOSP after allo-HSCT were enrolled. RESULTS: The median time from allo-HSCT to the occurrence of LOSP was 231 (90-1487) days. Twenty-eight patients harbored 1 or more pathogens (infectious LOSP, I-LOSP), whereas 22 did not harbor any pathogens (non-infectious LOSP, NI-LOSP). The 100-day survival rate of LOSP patients was 31.1%. Patients smoking before allo-HSCT (0% vs. 35.4%, P = 0.002) and male gender (20.0% vs. 61.9%, P = 0.026) had lower 100-day survival rate. Patients with a lower bronchoalveolar lavage fluid (BALF) neutrophil percentage had higher 100-day survival rate relative to those with higher BALF neutrophil percentage (45.5% vs. 16.7%, P = 0.012). The 100-day survival rate of patients with I-LOSP was lower than that of patients with NI-LOSP (19.1% vs. 46.9%, P = 0.043). Patients given late (≥1 week after LOSP diagnosis) and low-dose methylprednisolone (MP) therapy (≤2 mg/kg/day) had the best 100-day survival rate. In the multivariate analysis, nonsmoking before allo-HSCT and late and low-dose MP therapy were significantly associated with a better survival after LOSP. CONCLUSION: LOSP is a severe complication after allo-HSCT. The correct timing and corticosteroid dosage in the context of broad-spectrum antimicrobial therapy might further improve the outcomes of patients with LOSP.

Detection of human cytomegalovirus (CMV) DNA in feces has limited value in predicting CMV enteritis in patients with intestinal graft-versus-host disease after allogeneic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is difficult to diagnose. We aimed to evaluate the sensitivity and specificity of the detection of CMV DNA in feces for predicting CMV enteritis. METHODS: HSCT patients with intestinal graft-versus-host disease (GVHD) were enrolled if they met the following criteria: (i) underwent a colonoscopy and (ii) peripheral blood and feces specimens were available for CMV DNA detection within 24 h of colonoscopy. The colonoscopy histology was used as the gold standard for diagnosing CMV enteritis. RESULTS: Fifty-six patients underwent 58 colonoscopy examinations, and 7 were diagnosed as having CMV enteritis. Within 24 h of colonoscopy, 9 patients had detectable CMV in the feces and 19 patients had detectable CMV in the plasma, respectively. In the 7 patients with CMV enteritis, only 2 had detectable CMV in the stool, resulting in a sensitivity of 28.6%. In the 51 patients without CMV enteritis, 44 had no detectable CMV in the stool, with a specificity of 86.3%. CONCLUSION: We concluded that CMV detection in the feces was not a good predictor of CMV enteritis in patients with intestinal GVHD after allo-HSCT.

Effects of γ-ray irradiation on optical absorption and laser damage performance of KDP crystals containing arsenic impurities.

The effects of γ-irradiation on potassium dihydrogen phosphate crystals containing arsenic impurities are investigated with different optical diagnostics, including UV-VIS absorption spectroscopy, photo-thermal common-path interferometer and photoluminescence spectroscopy. The optical absorption spectra indicate that a new broad absorption band near 260 nm appears after γ-irradiation. It is found that the intensity of absorption band increases with the increasing irradiation dose and arsenic impurity concentration. The simulation of radiation defects show that this absorption is assigned to the formation of AsO44⁻ centers due to arsenic ions substituting for phosphorus ions. Laser-induced damage threshold test is conducted by using 355 nm nanosecond laser pulses. The correlations between arsenic impurity concentration and laser induced damage threshold are presented. The results indicate that the damage performance of the material decreases with the increasing arsenic impurity concentration. Possible mechanisms of the irradiation-induced defects formation under γ-irradiation of KDP crystals are discussed.

Association of miR-149C>T and miR-499A>G polymorphisms with the risk of hepatocellular carcinoma in the Chinese population.

We investigate the potential association of miR-149C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC). A matched case-control study of 152 cases and 304 controls were conducted. The miR-149C>T and miR-499A>G genotypes were analyzed using duplex polymerase chain reaction with restricted fragment length polymorphism. HCC patients were more likely to be smokers and drinkers, have hepatitis B and C virus infections, and a family history of cancer. The miR-149 CC genotype was associated with a reduced risk of HCC, while the miR-499 GG genotype was associated with an increased risk of HCC. However, we did not find that the miR-149 CC and miR-499 GG genotypes were associated with risk of HCC, and no interaction was found between miR-149C>T and miR-499A>G polymorphisms and hepatitis B virus infection. In conclusion, the miRNA-149C>T and miR-499A>G polymorphisms were found to play an important role for HCC risk in China. This finding could be useful in identifying people at high risk for the disease for early intervention.

[Clinical features and risk factors for invasive fungal sinusitis after allogeneic hematopoietic stem cell transplantation].

Objective: To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT. Methods: Nineteen patients with IFR after allo-HSCT at Peking University People's Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) . Results: Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10-59) years. The median IFR onset time was 68 (9-880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation (P=0.021) , hemorrhagic cystitis after transplantation (P=0.012) , delayed platelet engraftment (P=0.008) , and lower transplant mononuclear cell count (P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively (P<0.01) . Conclusion: Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.