[Clinical Study of Blinatumomab in the Treatment of Adult Relapsed/Refractory Ph-Negative Acute B-Lymphoblastic Leukemia].

OBJECTIVE: To investigate the efficacy and safety of CD19/CD3 bisecific monoclonalantibody (Blinatumomab) in the treatment of adult patients with relapsed / refractory Ph-negative acute B-lymphoblastic leukemia (R/R-B-ALL). METHODS: Ten adult R/R B-ALL patients were all treated with Blinatumomab. Each treatment cycle was administered for 28 days and stopped for 14 days. The dose was 9 µg/day for the first 7 days of cycle 1, and 28 µg/day for days 8-28 if there were no adverse reactions. From the second cycle onwards, the daily dose was 28 µg. The remission, survival time (EFS and OS) and adverse reactions were observed after treatment. RESULTS: Nine patients with curative effect could be evaluated. Four patients achieved CR after one course, and one patient achieved CR after two courses, the overall remission rate was 55.6%(5/9). The median EFS was 4 months (1-12 months), and the median OS was 6 months (2-44 months). Nine of the 10 patients had fever of different degrees. Serum levels of cytokines such as IL-6, IL-10, IL-17 and IFN-γ increased. Two patients resumed medication after 1 week of treatment interruption due to neurotoxicity and CRS, respectively. One patient was discontinued due to grade 3 CRS and died of tropical candidiaemia. CONCLUSION: Blinatumomab has a good response rate in the treatment of relapsed/refractory B-ALL patients, but the duration of remission is shorter. Drug-related adverse reactions are mainly CRS and neurotoxicity. Inflammatory factors IL-6, IL-10, IL-17 and IFN-γ can be used as indicators to monitor CRS. The bisspecificity MAbs provide an opportunity for subsequent allogeneic hematopoietic stem cell transplantation in R/R-B-ALL patients.

[High-Throughput Sequencing Technology for Detection of Gene Mutations in Myeloid Malignancies and Its Clinical Prognostic Significance].

OBJECTIVE: To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis. METHODS: A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed. RESULTS: In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08). CONCLUSION: The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.

Autoimmune Hemolytic Anemia After Cord Blood Transplantation: A Retrospective Single-Center Experience.

Objective: To describe the incidence, possible risk factors, and treatment options of autoimmune hemolytic anemia (AIHA) occurring after cord blood transplantation (CBT). Methods: We retrospectively analyzed the patients who underwent CBT at Peking University First Hospital between January 2004 and July 2022. Results: We totally identified thirty-six patients who received CBT. Median age was 27.5 years (range, 1.6-52). With a median 6 (range 0.6-10.0) years survivor follow-up, six patients developed AIHA (2 Evans syndrome included) at a median of 168 (range, 122-264) days post-CBT for 8% cumulative incidence density 3 years. Its mortality was 50% and mainly associated with concomitant infections (CMV reactivation rate nearly 100%). The possible risk factors for developing AIHA are CMV reactivation, GvHD and HLA mismatch. Conclusion: AIHA is a clinically significant common complication in recipients post-CBT. Corticosteroids combined with intravenous immunoglobulin (IvIg) is recommended for the treatment of warm antibody AIHA after CBT.

C-C chemokine receptor 5 and acute graft-versus-host disease.

BACKGROUND: The C-C chemokine receptor 5 (CCR5) is mainly expressed in a variety of immune cells. It interacts with multiple chemokine ligands that mediate the trafficking and recruitment of effector cells toward sites of inflammation. CCR5 not only plays a critical role in cell growth, activation, differentiation, adhesion, and migration but also participates in the development of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. METHODS: This is a literature review article. The research design method is an evidence-based rapid review. The present discourse aim is first to scrutinize and assess the available literature on CCR5 and acute GVHD. Standard literature and database searches were implemented, gathered relevant material, and extracted information was then assessed. RESULTS: CCR5 is a marker of GVHD effector cells, and CCR5 expression is elevated when acute GVHD occurs. CCR5 blockade with maraviroc in clinical trials results in a low incidence of acute GVHD. The immune mechanism includes that CCR5 blockade inhibits donor T cell migration and recruitment toward target organs, reduces the absolute numbers of donor T cells, is capable of slightly suppressing dendritic cell maturation, and reduces the percentage of Th1 and Th17 subsets. CCR5 blockade also inhibits internalization and activation of chemokines, inhibits proliferation and chemotaxis of T cells, and decreases the production of TNF-α and IFN-γ. In addition, there may be a form of crosstalk between CCR5 and CCR2. Inconsistently, infusion of CCR5-/- Tregs into lethally irradiated mice significantly increased the infiltration of CD4+ and CD8+ T cells into the liver, resulting in earlier and more severe GVHD. CONCLUSION: This review indicates that CCR5 plays an important role in pathogenesis and development of acute GVHD. Elucidating its role in different immune cells will aid the development of targeted therapeutic treatments.

Low-Dose 5-Aza and DZnep Alleviate Acute Graft-Versus-Host Disease With Less Side Effects Through Altering T-Cell Differentiation.

Objective: Previous studies showed that hypomethylating agents (HMAs) could alleviate acute graft-versus-host disease (aGvHD), but affect engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The combination of two different HMAs in lower doses might overcome this problem. This study aimed to evaluate the treatment effect of the combination of two HMAs-azacitidine (5-Aza) and histone H3K27 methyltransferase inhibitor 3-deazaneplanocin (DZNep)-for the prophylaxis of aGvHD after allo-HSCT and to explore the possible mechanisms. Methods: We first optimized the concentrations of individual and combinational 5-Aza and DZNep treatments to ensure no obvious toxicities on activated T cells by evaluating T-cell proliferation, viability, and differentiation. A mouse model of aGvHD was then established to assess the prophylactic efficacy of 5-Aza, DZNep, and their combination on aGvHD. The immunomodulatory effect on T cells and the hematopoietic reconstruction were assessed. Additionally, RNA sequencing (RNA-seq) was performed to identify the underlying molecular mechanisms. Results: Compared with single treatments, the in vitro application of 5-Aza with DZNep could more powerfully reduce the production of T helper type 1 (Th1)/T cytotoxic type 1 (Tc1) cells and increase the production of regulatory T cells (Tregs). In an allo-HSCT mouse model, in vivo administration of 5-Aza with DZNep could enhance the prophylactic effect for aGvHD compared with single agents. The mechanism study demonstrated that the combination of 5-Aza and DZNep in vivo had an enhanced effect to inhibit the production of Th1/Tc1, increase the proportions of Th2/Tc2, and induce the differentiation of Tregs as in vitro. RNA-seq analysis revealed the cytokine and chemokine pathways as one mechanism for the alleviation of aGvHD with the combination of 5-Aza and DZNep. Conclusion: The combination of 5-Aza and DZNep could enhance the prophylactic effect for aGvHD by influencing donor T-cell differentiation through affecting cytokine and chemokine pathways. This study shed light on the effectively prophylactic measure for aGvHD using different epigenetic agent combinations.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update.

The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China.

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS: Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Impact of Low-Dose rATG Prior to Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: Reduced Risk of Chronic Graft-versus-Host Disease and Improved Survival Outcomes.

PURPOSE: To explore the efficacy of low-dose rabbit antithymocyte globulin (rATG) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) for patients with acute leukemia or myelodysplastic syndrome. PATIENTS AND METHODS: We performed a retrospective study of 79 patients with hematologic malignancies who received MSD-HSCT. All patients received standard graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine, mycophenolate mofetil and short-term methotrexate. Among them, 38 were administered 5 mg/kg rATG as part of GVHD prophylaxis. Clinical outcomes including overall survival (OS), GVHD and relapse were analyzed. RESULTS: No graft failure occurred in the antithymocyte globulin (ATG) or non-ATG group. The cumulative incidences of grade 2-4 and 3-4 acute GVHD at day +100 were 13.3% versus 19.5% (p=0.507) and 5.7% versus 15.2% (p=0.196), respectively. The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4% (p=0.039), and those of extensive cGVHD were 12.9% and 40.0% (p=0.015), respectively. In a multivariate analysis, the use of low-dose rATG was an independent protective factor for extensive cGVHD (hazard ratio [HR] 0.256; 95% confidence interval [CI], 0.080 to 0.822, p=0.022). The 2-year OS was 88.1% and 68.4% (p=0.038), respectively, and the use of low-dose rATG was the only protective factor in the multivariate analysis (HR 0.216; 95% CI, 0.059 to 0.792, p=0.021). There was no significant difference between the two groups in terms of the 2-year cumulative incidence of relapse, leukemia-free survival or GVHD-free and relapse-free survival. CONCLUSION: Low-dose rATG used in MSD-HSCT as part of the conditioning regimen results in a reduced incidence of cGVHD and improves survival outcomes.

[Clinical Analysis for Patients with AML Treated after Allo-HSCT].

OBJECTIVE: To analyze risk factors that affect survival and relapse of AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate the therapy choices after AML relapse. METHODS: Clinical data of 180 AML patients achieved complete remission (CR) before HSCT from January 2009 to December 2018 treated in our center were analyzed retrospectively. Risk factors for survival and relapse after allo-HSCT were analyzed by COX regression. RESULTS: Among 180 AML patients, 134 survived (74.4%), 46 patients died (25.6%), and 40 patients relapsed (22.2%). The rate of overall survival (OS), event-free survival (EFS) and cumulative rate of relapse in 5-years was 74.3%、42.5% and 25.0%, respectively. High-risk, adverse cytogenetics, CR2 at HSCT and no cGvHD were independent risk factors that affect OS. CR2 at HSCT, high-risk were independent risk factors that affect EFS. High-risk, MRD+ after one course of induction therapy, adverse cytogenetics and no cGVHD were independent risk factors that affect relapse. The OS rate of relapse patients could be improved by the usage of hypomethylation agents combined with G-CSF mobilized donor lymphocyte infusion (DLI), and 2-year OS rate was 62.5%. CONCLUSION: The survival rate of AML is greatly improved by allo-HSCT, but relapse is still one of the most important factors that influence survival of the AML patients. The maintenance therapy of hypomethylation agents combined with DLI may be a new effective treatment option for patients who relapse after HSCT.

Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study.

PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS: From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.

[Clinical Analysis of Dasatinib and Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 19 newly diagnosed as Ph+ ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed. RESULTS: There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively. CONCLUSION: First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of Ph+ALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.

[Analysis of Decitabine Therapeutic Effeicacy for Patients with Relapsed MDS/AML and High-Risk AML Patients after HSCT].

OBJECTIVE: To investigate the therapeutic efficacy of using decitabine as maintenance therapy for patients with relapsed MDS/AML and as prophylactic therapy for patients with high-risk AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 10 patients with MDS/AML from November 2016 to May 2018 were analyzed retrospectively. Among 10 patients there were 4 cases of AML, 2 cases of MDS, and 4 cases of AML transformed from MDS (t-AML). The 10 patients were devided into 2 groups: the relapsed group (n=8) and the prophylactic group (n=2). In relapsed group the decitabine was used as maintenance therapy after achieved complete remission (CR) with decitabine chemotherapy. In prophylactic group the decitabine was used as prophylactic therapy if the patients didn't appear the symptom of graft-versus- host-disease (GVHD) during 30 to 45 d after allo-HSCT. Eight patients received G-CSF-mobilized donor lymphocyte infusion (DLI). The dosage of decitabine for maintenance therapy and prophylactic therapy was 5 mg/m2 for 7 to 10 days every 4 to 6 weeks, as 1 cycle, amount to 3 to 7 cycles. The dosage was adjusted by the endurance of patients. RESULTS: Until Nov 30, 2018, 7 out of 10 patients survived. The average survival time was 15.5±1.9 months. 1-year OS rate was 64.0%. Six patients appeared aGVHD, and four patients appeared cGVHD. CONCLUSION: The usage of decitabine combined with DLI in patients with relapsed MDS/AML and high-risk AML after allo-HSCT can prolong lives of patients, reduce relapsed rate, and provide the probability for long time survival.

Decitabine-Containing Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Intermediate- and High-Risk Myelodysplastic Syndrome/Acute Myeloid Leukemia: Potential Decrease in the Incidence of Acute Graft versus Host Disease.

PURPOSE: To evaluate the role of Decitabine in the allo-HSCT conditioning regimen for intermediate- and high-risk patients with MDS or AML. PATIENTS AND METHODS: Retrospective analysis of data pertaining to 76 intermediate- and high-risk patients with MDS or AML who underwent allo-HSCT between December 2005 and June 2018 at the Peking University First Hospital. Forty patients received Decitabine-containing conditioning regimen before transplantation, while thirty-six patients received regimen without Decitabine. RESULTS: Over a median follow-up of 40 months (range, 1 to 155), the cumulative incidence of grade II to IV acute graft versus host disease was 12.4% [95% confidence interval (CI) 4.9-30.9%] in the Decitabine group and 41.5% (95% CI 28.1-61.2%) in the non-Decitabine group (P=0.005). On multivariate analysis, Decitabine-containing conditioning regimen was found to protect against grade II to IV aGVHD (HR=0.279, 95% CI 0.102-0.765, P=0.013). Incidence of respiratory infection in the Decitabine and non-Decitabine groups was 22.5% and 52.78%, respectively (P=0.012). No significant between-group difference was observed with respect to 3-year OS, DFS, or RR (P=0.980, 0.959, and 0.573, respectively), while the median relapse time was longer in the Decitabine group [7 months (range, 2-12) versus 3 months (range, 2-4), P=0.171]. Decitabine-containing conditioning showed a tendency for lower relapse rate among higher risk patients, as assessed by IPSS R; however, the between-group difference was not statistically significant (P=0.085). CONCLUSION: Inclusion of Decitabine in the conditioning regimen for allo-HSCT in intermediate- and high-risk patients may lower the incidence of aGVHD and respiratory infections, and contribute to longer median relapse time.

[Preliminary Study on the Characteristic of Plasma Cytokine Profiles in Patients with Idiopathic Multicentric Castleman Diseases].

OBJECTIVE: To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD). METHODS: The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively. RESULTS: Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P＜0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1ß and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P＜0.01）, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P＜0.05）, no significant difference of the rest cytokines was found between iMCD and the control group. CONCLUSION: IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma.

BACKGROUND: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). METHODS: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. RESULTS: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. CONCLUSION: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

[Pathological Features, Treatment Options and Prognosis Assessment of Patients with Bone Lymphoma in Real-World].

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION: Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.

[A Preliminary Study on the Expression of CD160 on NK Cells and Its Mechanism of Mediating NK Killing Effect].

OBJECTIVE: To investigate the expression of CD160 on the surface of human natural killer (NK) cells and its possible relationship with hematological malignancies. METHODS: CD160 expression on human leukemia cell line NK92 cells was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The proliferation characteristics and cell surface markers of this cell line were determined. Cytotoxicity of NK92 against 2 human myeloid leukemia cell lines, K562 and THP-1 was analyzed ex vivo. CD160 blocking antibody CL1-R2 was employed to clarify its role in NK cell mediated cytolysis. Then, the expression of CD160 on NK cells in peripheral blood from various patients with hematological malignancies were measured by flow cytometry. RESULTS: The mRNA and protein levels of CD160 expressions on NK92 cells were confirmed by RT-PCR and Western blot, respectively. The flow cytometry results demonstrated that the strong positive expression of CD160 could be detected on the NK92 cell surface. NK92 could effectively kill K562 and THP-1 cells, while the cytolysis effect was abrogated in the presence of CD160 blocking antibody CL1-R2. The high levels of HVEM were expressed on both target cells, but the HLA class I molecules were absent on K562. The expression of CD160 on CD3-CD56+ NK cells in peripheral blood from patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients was significant lower than that in the normal controls (P<0.05). CONCLUSION: The cytolysis function of human NK cells is mediated partially by CD160 molecule. The decrease of CD160 expression on NK cells from patients with various hematological malignancies implies that down-regulation of CD160 expression may be a novel mechanism of tumor immune escape.

[Incidence of Bone Marrow Involvement in Different Pathological Type Lymphoma Patients].

OBJECTIVE: To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma. METHODS: The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) and 18F-FDG PET/CT, were analyzed retrospectively in 702 cases of newly diagnosed lymphoma with bone marrow assessment in our hospital from October 2000 to September 2016. If one of the above-mentioned 4 tests showed positive, the lymphoma patient was judged as bone marrow involved. RESULTS: The incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively. CONCLUSION: The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.