[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

[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.

[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.

[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.

[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.

[Efficacy and safety of secondary allogeneic hematopoietic stem cell transplantation in 70 patients with recurrent hematologic malignancies after transplantation].

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.

[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.

[Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation].

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

[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.

[A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia].

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

[A 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.

[Safety of rabbit anti-human thymocyte immunoglobulin in second allogeneic hematopoietic stem cell transplantation for patients with hematological diseases].

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.

[BK virus encephalitis in children with hematopoietic stem cell transplantation].

Objective: To explore the morbidity, mortality, median onset time, clinical characteristics, diagnosis, treatment, and outcome of BK virus (BKV) central nervous system infection in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and improve the understanding, clinical diagnosis, and treatment of the disease. Methods: Seven hundred and nine children who received haploid HSCT treatment in Peking University People's Hospital from January 1, 2015 to December 31, 2020 were reviewed. Fourteen patients were diagnosed with BKV central nervous system infection, and their clinical characteristics, treatment process, and prognosis were analyzed. Results: The incidence of BKV central nervous system infection was 1.97% (14 cases) , mostly in men (12 cases) , with a median age of 11 years old and median onset time of 55 d. Additionally, most of the cases showed disturbance of consciousness and seizures (seven cases) . Furthermore, 14 cases were treated with acyclovir and ganciclovir alone or with gamma globulin. Nine cases were cured, of which one died of viral encephalitis and four of other diseases, with a mortality rate of 35.7%. Conclusion: Individuals with central nervous system involvement by BKV infection, usually show signs and symptoms of acute encephalitis, with some cases being accompanied by meningeal involvement. Although BKV encephalitis was diagnosed and actively treated with drugs, many patients still died of multiple organ failure or other complications. Therefore, when there are neurological symptoms and hemorrhagic cystitis in patients with allo-HSCT, it is necessary to be highly vigilant against BKV central nervous system infection. This helps to make clear diagnosis and treatment quickly; thus, improving the survival rate and quality of life of patients with 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.

[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 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.

[Analysis of the efficacy and safety of plerixafor combined with G-CSF in plasma cell disease mobilization].

Objective: To analyze the effect and safety of plerixafor combined with G-CSF mobilization in plasma cell disease. Methods: The clinical baseline data, success rate of collection, and adverse reactions of consecutive cases of plasma cell disease were analyzed retrospectively, where the patients received plerixafor combined with G-CSF for autologous hematopoietic stem cell mobilization in Peking University People's Hospital from January 2018 to December 2019. Results: Forty-nine patients with plasma disease were included, of which 39 (79.6% ) were multiple myeloma, 8 (16.3% ) were amyloidosis, and 2 (4.1% ) were monoclonal gammopathy of renal significance. A total of 16 patients (32.7% ) had renal insufficiency, and 7 patients (14.3% ) had previous collection failure. The median times of apheresis was 1 (1-3) , median days of apheresis was 2 (1-3) days, 47 patients (95.9% ) were successfully collected for once, and the success rate of collection for twice was 100% after using plerixafor for mobilization. In 16 patients with renal insufficiency, collection was successful in 5 patients (31.3% ) on the first day, while aphresis was required in 8 patients (50% ) on the second day and 3 (18.8% ) on the third day. The main adverse reactions were fatigue, insomnia, abdominal pain, diarrhea, dizziness, and arthralgia. A total of 37 patients underwent autologous hematopoietic stem cell transplantation with 11 (8-13) days for neutrophil engraftment, and 11 (9-26) days for platelet engraftment. Conclusions: Plerixafor combined with G-CSF has a high success rate in mobilizaion of autologous hematopoietic stem cells in patients with plasma cell disease with minimum side effects, even in patients with renal insufficiency.

[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.