Renal impairment (RI) is a common complication of multiple myeloma (MM), which is associated with poor prognosis. Here, we revealed the association between regular examination data and RI incidence, RI response and survival in newly diagnosed multiple myeloma (NDMM) patients. A retrospective analysis was conducted on the initial clinical data of 647 NDMM patients, comprising 193 patients (29.83

Purpose To evaluate the efficacy and safety of second allogeneic hematopoietic cell transplant (allo-HCT) in patients with myeloid hematologic malignancies who relapsed or encountered graft failure after the first allo-HCT. Patients and Methods This retrospective analysis included 12 cases with acute myeloid leukemia or myelodysplastic syndrome who underwent a second allo-HCT at Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital between January 2020 and May 2024. There were 8 male and 4 female, the median age at was 40.5 (18-56), 9 patients with acute myeloid leukemia and 3 cases with myelodysplastic syndrome. Donor at first allo-HCT: 10 from related haploidentical donor, and 2 from matched sibling donor. 7 cases used a different donor for second allo-HCT: 2 matched unrelated donor, 1 matched sibling donor, 4 related haploidentical donor. The performance status assessment by ECOG score were：1 case scored 0, 1 case scored 1, 6 cases scored 2, 3 cases scored 3, 1 case scored 4. As for Hematopoietic Cell Transplantation-Comorbidity Index(HCT-CI) score：10 cases scored 1，1 case scored 2 and 1 case scored 3. The time interval between two allo-HCT: 4 cases within 180 days，8 cases beyond 180 days. Strongly positive DSA were detected in 2 cases. The disease status assessment before second allo-HCT: only 4 cases were in complete remission. Conditioning regimen: 3 patients encountering graft failure received reduced intensity conditioning, while 9 relapsing patients received total body irradiation (8Gy) and thiotepa (5mg/kg for 2 days) based myeloablative conditioning. GVHD prophylaxis included porcine anti human lymphocyte immunoglobulins, tacrolimus, methotrexate and/or anti-CD25 antibody. Our primary endpoint was OS, defined as time from transplantation to 1 year and last follow-up post-HCT or date of death. Statistical analyses were performed using the statistical package SPSS version 17. Results Engraftment was achieved in 10 patients (including those 2 cases with strongly positive DSA), the median time of neutrophil engraftment was 10(9-16) days. 2 patients died on +4 and +8 day after second allo-HCT, were excluded from further analysis. 10 patients were in complete remission by day 30 post second allo-HCT, no relapse were detected during the follow up. The median follow up was 364 (72-1007) days. 5 patients died and the other 5 survived by 2024.9.30, causes of death including severe pneumonia, multiorgan failure, and severe GVHD. The median overall survival was 535(95%CI:339-730)days, the 1 year cumulative survival rate was 78%，and the 2 year cumulative survival rate was 35%. Univariate analyses suggested ECOG (＞2) and HCT-CI(＞1) score were correlated with patient survival after second allo-HCT. Conclusion The findings of our current study indicate that a second allo-HCT is a reasonable treatment choice for AML and MDS patients relapsing or encountering graft failure after a first allo-HCT, complete response and survival benefit may be anticipated particularly in those with better performance status and fewer comorbidities.

PTCL are a heterogeneous group of lymphoproliferative disorders generally associated with dismal clinical outcomes, especially in the R/R context. Allo-SCT as the potentially curative therapeutic option for R/R PTCL patients, fails to provide lasting tumor control. Our previous research has confirmed that an ATG-based conditioning regimen is a feasible and effective alternative for patients with aggressive TCLs. A retrospective analysis was conducted on patients with advanced R/R PTCL who underwent allo-SCT at our center. All the patients treated with the TBI-ATG-based myeloablative conditioning regimen. Thirty-seven R/R PTCL patients, with a median age of 51 years at transplantation, were analyzed. All patients had experienced relapse or primary progression of T-cell lymphoma prior to allo-SCT. Specifically, 5 patients had achieved PR in response to their last salvage treatment and 32 patients had PD at the start of conditioning for allo-SCT. All patients successfully engrafted and achieved full donor chimerism. At a median follow-up of 25.8 months, the 2-year OS and PFS were 61.69% and 58.73%, respectively. Thirty-one cases underwent haplo-allo-HSCT. The 2-year OS and PFS for this subgroup were 68.09% and 58.34%, respectively. Five cases who achieved PR prior to allo-SCT, with a median follow-up of 38.5 months, all are alive and disease-free. Additionally, in the subgroup of 32 cases who were in PD status prior to allo-SCT, the 2-year OS and PFS were 54.89% and 50.77%, respectively. The 2-year relapse rate (RR) was 31.59% and 2-year relapse-related mortality (RRM) was 16.95%. The 2-year NRM was 25.53%.

Objective:To investigate the efficacy and safety of a treatment regimen combining Daratumumab(Dara)with Venetoclax(Ven)in patients suffering from relapsed/refractory T-lymphoblastic leukemia/lymphoma(T-ALL/LBL).Methods:From January 2023 and January 2024,twelve patients with relapsed/refractory T-ALL/LBL received a combined treatment regimen based on Dara and Ven.The cohort consisted of 9 males and 3 females,with a median age of 25(range:15-57)years.Within each 28-day treatment cycle,Dara was scheduled to administer at a dosage of 16 mg/kg once weekly for 4 weeks,while Ven was given at 400 mg daily for 21 days,within each 28-day cycle.Additionally,some patients received liposomal mitoxantrone and pegaspargase as part of their treatment.Results:The combined regimen of Dara and Ven achieved an overall response rate(ORR)of 75.0％,with a complete remission(CR)rate of 58.8％.Among the 12 patients,seven had not previously undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT).Of these,four achieved CR,one a-chieved partial remission(PR),and two did not respond.Of the four CR patients who subsequently underwent allo-HSCT as consolidation therapy,three remained disease-free,while one relapsed.The PR patient and one non-remission(NR)patient died due to disease progression after different chemotherapy regimens.Another NR patient died early after salvage transplantation due to infection.Five patients were enrolled post-allo-HSCT.Four of them relapsed after the first transplantation,and one developed a secondary neoplasm.Among these,three pa-tients(60.0％)achieved CR,with two remaining disease-free;one relapsed and underwent a second allo-HSCT.Of the other two patients,one achieved PR,and one failed to respond.Both of them died due to disease progres-sion.For all 12 patients,the one-year overall survival(OS)was 58.3％(95％CI 27.0％-80.1％),and the median survival was not reached.The one-year progression-free survival(PFS)of 9 patients who achieved response was 53.3％(95％CI 17.7％-79.6％),The one-year OS for the 5 patients after transplantation was 60.0％(95％CI 12.6％-88.2％),and the PFS of 4 responded patients was 50.0％(95％CI 5.8％-84.5％).Only 2 patients expe-rienced infusion reactions related to Dara with no serious treatment-related adverse events.Conclusion:The Dara and Ven regimen demonstrate a high response rate and well-tolerated treatmnet option for patients with relapsed/refractory T-ALL/LBL.It can serve as a bridging treatment for patients who have not undergone allo-HSCT.For patients who experience relapse after allo-HSCT,it can also be used as a maintenance therapy to extend disease-free survival.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient’s complete remission has persisted for 20 months after HSCT.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) serves as a critical therapeutic approach for various malignant and non-malignant hematopoietic disorders. Notwithstanding successful hematopoietic recovery in most patients following allo-HSCT, a subset may encounter delayed platelet engraftment (DPE), a prevalent and potentially serious complication that stems from myeloablative conditioning. Occurring in approximately 5%-37% of allo-HSCT recipients, DPE is a known harbinger of increased transplant-related mortality and diminished quality of survival. Despite its clinical significance, a well-established standard treatment protocol for post-allo-HSCT DPE remains elusive. Multiple platelet transfusions, often administered in such cases, not only exacerbate the economic burden but also induce toxicities, thereby undermining the patient's quality of life. An alternative to platelet transfusion lies in the utilization of thrombopoietin-receptor agonists (TPO-RAs), advocated for enhancing platelet engraftment. These agents interact with the thrombopoietin receptor, stimulating intracellular signaling pathways inclusive of JAK/STAT, PI3K/AKT, and ERK1/2, which in turn, promote megakaryocyte proliferation and differentiation, thereby augmenting platelet production. Hetrombopag, a novel, orally administered, non-peptide, small-molecule TPO-RA, has been validated to effectively boost platelet engraftment and reduce the necessity for platelet transfusions post-allo-HSCT in a pilot study. Our study sought to investigate the effectiveness and safety of hetrombopag in treating DPE following allo-HSCT within a real-world setting. Methods: In this retrospective study, we evaluated adult patients with hematopoietic disorders who underwent allo-HSCT and subsequently experienced DPE in our center, treated with hetrombopag between March 2022 and April 2023. Given the lack of a consensus definition, we deemed DPE as a platelet count (PLT) < 20 × 10 9/L or a significant and rapid decreasing trend past day 28 post-allo-HSCT. Hetrombopag dosages of 2.5 mg, 5 mg, or 7.5 mg/day were prescribed based on individual patient conditions. Response criteria post-treatment were as follows: complete response: PLT > 50 × 10 9/L without platelet transfusion; partial response: PLT between 20 and 50 × 10 9/L without platelet transfusion; no response: PLT < 20 × 10 9/L. Results: A total of 20 patients were included in the analysis, with a median age of 52, and 60% of them were male. Hetrombopag administration commenced at a median of 58 days following allo-HSCT at a median dose of 5 mg/day, with a median treatment duration of 44 days. The initial platelet count was 24.5 × 10 9/L and serum ferritin levels stood at 3351.1 ng/mL. Post-hetrombopag treatment, platelet counts escalated to 67.5 × 10 9/L while serum ferritin levels decreased to 2726.0 ng/mL. Of the 20 patients, 13 patients (65%) exhibited a complete response, 6 patients (30%) achieved a partial response, and 1 patient (5%) displayed no response. Hetrombopag was well tolerated with only 5 patients reporting increased alanine aminotransferase/aspartate aminotransferase or total bilirubin levels (all grade 1 or 2), and the association with hetrombopag was undetermined. Conclusion: Our findings suggest that hetrombopag yields a sustained response with acceptable tolerability in patients who experienced DPE following allo-HSCT, and could potentially offer a novel approach for managing such patients. Future large-scale, prospective studies are warranted to further assess the potential benefits of hetrombopag for improving patient outcomes following allo-HSCT.

Objective: Immunosuppression intensified conditioning regimen has been applied for 10 patients with strong positive pre-transplantation Donor specific Anti-HLA Antibodies (DSAs) undergoing Haploidentical Hematopoietic Stem Cell Transplantation (HSCT), its effects on engraftment of hematopoietic stem cell were examined. Methods: Characteristics of 10 consecutive patients with strong positive pre-transplantation DSAs were retrospectively analyzed, including gender, age, diagnosis, disease status pre-transplantation, presence of DSA, conditioning regimens, engraftment, graft versus host disease (GVHD) incidence and survival. Results: Ten patients [3 males vs 7 females, median age 53.5(36-64)] received immunosuppression intensified conditioning regimen: Fludarabine plus busulfan (FluBu) combining total body irradiation and cyclophosphamide (TBI-Cy). DSA levels gradually decreased in all patients after preparative conditioning, and the mean fluorescence intensity (MFI) values dropped significantly (P＜0.003). The average MFI values dropped 40% at day 7 post-HSCT, 8 cases acquired hematopoietic reconstitution, the median time of neutrophil engraftment was 15.6(10-16) days, and 19(13-22) days for platelet engraftment. One case had primary graft failure and another one had poor graft function. After a median follow-up of 12.5(1.5-27) months, 7 cases remained in disease remission state with negative DSA assay, including 2 cases with MFI values higher than 20000 pre-transplantation. Conclusions：Immunosuppression intensified conditioning regimen can efficiently decrease the Donor specific Anti-HLA Antibodies (DSA) level, which leads to lowered chances of primary graft failure.

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

Objectives: To investigate the efficacy of short-term substitution of Recombinant humanized anti-CD25 monoclonal antibody (anti-CD25 rhMAb) as aGVHD prophylaxis in CNIs intolerant patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Methods: From August 2021 to August 2022, seventeen patients with refractory hematologic malignancies after salvage Allo-HSCT were enrolled in our study. All were treated with anti-CD25 rhMAb as GVHD prophylaxis due to severe CNIs intolerance such as acute renal dysfunction, central nervous system complications (CNSC) or endothelial injury syndromes. There were seven males and ten females, with a median age of 43 years (18-67). After the withdrawal of CNIs, anti-CD25 rhMAb was applied at 1mg/Kg once a week until the reinstitution of CNIs or mTOR inhibitors. Results: Anti-CD25 rhMAb was initiated at a median of 5 days (range: 1-32) after HSCT. The median duration of substitution was 20(7-120) days. All achieved neutrophil engraftment after a median of 12 days (range: 10-17). Thirteen patients had platelet engraftment after a median of 13 days (range: 11-20). Four patients did not achieve stable platelet engraftment. Eight patients (47.1%) developed Grade II-IV aGVHD, and four (23.6%) developed Grade III-IV aGVHD. Only one patient died of aGVHD. Until December 31, 2022, Seven of 17 patients died. The longest follow-up time of the survivors was 347 days, and the median survival was not reached. Overall survival (OS) at six months was 62.6%. OS at six months was 80.0% in the subgroup with CNSC. Conclusions: When CNIs intolerance occurs during Allo-HSCT, Short-term replacement of CNIs with anti-CD25 rhMAb is an optional approach, which may provide a promising aGVHD prophylaxis for patients with CNIs intolerance.

Objectives: To evaluate the clinical outcomes and safety of haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT)with total body irradiation (TBI)/rabbit Anti-thymocyte globulin (rATG) based conditioning regimen in chemotherapy-resistant advanced-stage peripheral T-cell lymphoma (PTCL). Methods: From September 2019 to December 2022, eleven chemotherapy-resistant advanced-stage PTCL patients who underwent haplo-HSCT were enrolled in our study. All of them received TBI/rATG-based conditioning regimen in our centers. Results: ①Among 11 patients, there were 6 males and 5 females with a median age of 40(range：22~58) years old. Six cases of them are peripheral T-cell lymphoma not otherwise specified (PTCL NOS), 3 cases are angioimmunoblastic T-cell lymphoma (AITL), 1 case is large-cell transformation of mycosis fungoides (MF-LCT), and 1 case is T-cell large granular lymphocytic leukemia(T-LGLL). The Lugano stage was III or IV in all cases, and 8 patients had B symptoms. The median number of previous chemotherapy exposure before transplantation was 4 (range: 2~10) lines and the disease status before transplantation was progressive diseases (PD) in all cases. The median time from diagnosis to transplantation was 17(range：6~36) months.②The conditioning regimen consisted of TBI 2Gy d-8, 4Gy from day-7 to -6, rATG 2.5 mg/kg/d day-5 to -2, etoposide 15mg/kg/d day-5 to -4, cyclophosphamide (CTX) 50mg/kg/d, day-3 to -2. The patients with central nervous system involvement received a regimen of thiotepa 5 mg/kg/d， from day -5 to -4 instead of CTX and etoposide, and add 2.0 g/m2 of cytarabine twice a day, from day -3 to day -2 into the conditioning.③All patients were successfully engrafted. Only one patient developed Grade III-IV acute graft-vs-host disease (aGvHD). Among the 8 survivors, 4 cases developed chronic graft-vs-host disease (cGvHD).④After transplantation, CR was obtained in 9 patients. ⑤Regimen related toxicities: all were non-fatal. Hematopoietic suppression occurred in all patients after conditioning. Three patients had diarrhea and four had mucositis and three had elevated transaminase/bilirubin levels. Seven patients had infections.⑥The 1-year cumulative non-relapse mortality (NRM) and 1-year cumulative incidence of relapse (CIR) was 22.5±14.0% and 20.2±12.7%, respectively. The 1-year overall survival (OS) and 1-year disease-free survival (DFS) was 72.7±13.4% and 63.6±14.5%, respectively Conclusions: TBIand rATG based conditioning regimen is effective and safe for haplo-HSCT in chemotherapy-resistant advanced-stage PTCL.

目的 分析多发性骨髓瘤浆细胞胞浆中的常见包涵体,为多发性骨髓瘤浆细胞形态学诊断提供参考.方法 采用瑞-吉染色法,查找1例κ轻链型多发性骨髓瘤患者骨髓细胞涂片中极罕见的浆细胞,并结合国内外相关文献,对类似病例进行回顾分析.结果 形态学检查发现可能为嗜天青颗粒的大小不等、较不规则、紫红色的包涵体样颗粒.相关研究结果表明,多发性骨髓瘤的浆细胞胞浆常见包涵体样颗粒包括Russell小体、Mott细胞、Dutcher小体、类Auer小体等,可能有一定的临床意义.结论 罕见异常浆细胞的形态学诊断对轻链型多发性骨髓瘤和浆细胞中出现包涵体的多发性骨髓瘤的诊断有重要的参考价值.

For successful transplantation using a haploidentical donor, it requires effective depletion of T cells to reduce the risk of graft-versus-host disease (GvHD) and prevent serious GvHD.Contemporary practice of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) frequently adopts in vivo T-cell depletion strategies: a monoclonal antibody against T cells using antihuman thymocyte immunoglobulin (ATG) [1,2] or posttransplant cyclophosphamide (PTCy) based regimen [3,4].The ATG-based regimen was one of the most commonly used GvHD prophylaxis for Haplo-HSCT in China but remaining an issue of higher risk of acute GvHD (aGvHD) up to 40% incidence [1, 2] as well as cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection.PTCybased regimen had outstanding outcomes of GvHD prevention in Haplo-HSCT with bone marrow grafts with 21-34% of incidences of grades II-IV aGvHD.However, by substituting BM graft with peripheral blood stem cell (PBSC) grafts, the incidence of grades II-IV aGvHD increased in Haplo-HSCT even after the use of PTCy-based regimens for GvHD prophylaxis [5,6].Accordingly, there is room for further improvement of GvHD reduction when the haploidentical transplant was performed using a PBSC graft.Thus there is a practical demand for more powerful GvHD prophylaxis for haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) beyond ATG-based or PTCy-based regimens.Recently, we have applied a novel regimen of combining low dose ATG (5 mg/kg) with low dose PTCy (one dose of 50 mg/kg) (low dose ATG/PTCy) for prevention of GvHD in Haplo-HSCT with PBSC grafts combined with unrelated single cord blood (UCB) in our center [7].The novel GvHD prophylaxis regimen showed promising activity with grades II-IV aGvHD of 19.4%, which was significantly lower than that with other regimens including standard PTCy regimen (2 days Cy 100 mg/kg) [4][5][6][7].Some studies [8][9][10][11] reported that UCB in combination with CD34 + selected PBSCs from a related mismatched donor were transplanted into recipients with fast engraftment, low incidences of GvHD, and promising long-term results.According to the results in these studies, an UCB was co-transfused with PBSCs in our study, while an UCB as the third party cells might obscure the effects of the novel regimen in the prophylaxis of GvHD.Thus to confirm the effects of the novel regimen on

目的:探讨异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后出血性膀胱炎(hemorrhagic cystitis,HC)发生的危险因素,为HC的预防和治疗提供临床依据.方法:对2018年1月至2020年1月在本院完成allo-HSCT的188例患者的病例资料进行回顾性分析.选择影响allo-HSCT后HC发生的相关临床参数进行单因素和多因素分析.结果:HC的发生率为20.7％(39/188),中位年龄41岁.尿BK病毒(BK virus,BKV)阳性检出率76.9％(30/39).轻度HC 33例,重度HC 6例.HC发生的中位时间为30(-2～69)d,其中38例为迟发型HC,1例为早发型HC,HC中位持续时间为16(5～82)d.巨细胞病毒(cytomegalovirus,CMV)血症(-0.000)以及急性移植物抗宿主病(acute graft versus host disease,aGVHD) (P=0.006)是HC发生的独立危险因素.结论:定期检测CMV-DNA,积极有效的抗病毒治疗是预防HC发生的有效措施.积极有效地预防和治疗aGVHD是预防HC的发生、促进HC恢复的有效措施.

目的:研究异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Mlo-HSCT)治疗伴TP53基因突变髓系肿瘤患者的疗效和预后相关因素.方法:纳入2016年1月至2019年12月我院allo-HSCT治疗的患者267例,回顾分析31例伴TP53突变髓系肿瘤患者的临床特征和治疗结果,并与236例无TP53突变患者比较分析.结果:伴和不伴有TP53突变患者中位年龄分别为55(26～65)岁和41(7～67)岁(P=0.001);移植时突变组缓解期患者比例(45.2％)显著低于无突变组(64.8％)(P=0.004).供受者ABO血型相合比例显著低于无突变组(35.5％比53.0％,P=0.013).所有移植时未缓解(no remission,NR)患者移植后均获得完全缓解(complete remission,CR);植入率、粒系和巨核系植入时间2组无差别.伴TP53突变患者Ⅱ～Ⅳ度急性移植物抗宿主病(acute graft versus host disease,aGVHD)发生率(33.3％)与无突变组相当(30.0％)(P=0.648);移植后1年中重度慢性GVHD (chronic GVHD,cGVHD)发生率2组相当(18.5％比20.3％,B=0.831).TP53突变患者与无突变组患者2年累积复发率(cumulative incidences of relapse,CIR)分别为65.6％±1.4％比15.1％±0.1％ (P=0.035),2年无复发生存(relapse free survival,RFS)率(10.1％±8.6％比72.2％±3.7％,P＜0.001)及总生存(overall survival,OS)率(19.4％±10.7％比74.0％±3.4％,P＜0.001)显著降低.多因素分析显示,年龄(≥55岁)、移植时NR同时是伴TP53突变的急性髓系白血病(acute myeloidleukemia,AML)和骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者OS和RFS的预后不良因素,移植前NR患者复发风险是CR患者的3.591倍[风险比(hazard ratio,HR)=3.591,95％置信区间(confidence interval,CI):1.136～11.355,P=0.029].减低强度预处理(reduced intensity conditioning,RIC)预处理方案、高危核型和未发生cGVHD分别是OS和RFS的预后不良因素.发生cGVHD患者的CIR率显著下降(HR=0.558,95％CI: 0.082～5.493,P=0.034).结论:早期获得缓解并行allo-HSCT是治疗伴TP53突变的AML和MDS的首选方法,高龄、高危核型、移植时NR及RIC预处理方案及未发生cGVHD是影响TP53突变患者移植后生存时间的危险因素.

Background: Macrophages in the tumor microenvironment play a critical role in tumorigenesis and anti-cancer drug resistance. Burkitt's lymphoma (BL) is a B-cell non-Hodgkin's lymphoma with dense macrophage infiltration. However, the role for macrophages in BL remains largely unknown. Methods: B7-H1, a transmembrane glycoprotein in the B7 family, suppresses T cell activation and proliferation and induces the apoptosis of activated T cells. The expression of B7-H1 in BL clinical tissues was determined by streptavidin-peroxidase immunohistochemistry. The mutual regulation between macrophages and BL Raji cells was investigated in a co-culture system. The cell proliferation and cell cycle distribution of Raji cells were determined using BrdU staining coupled with flow cytometry. CD163, CD204 and B7-H1 expression was assessed by flow cytometry and Western blot. Cell invasion was analyzed by Transwell assay. The expression of cytokines was detected by quantitative RT-PCR. Immunofluorescence and allogeneic T-cell proliferation assays were used to compare the expression of B7-H1, p-STAT6, or p-STAT3 and CD3+ T cell proliferation treated with or without amphotericin B. Results: B7-H1 was highly expressed in tumor infiltration macrophages in most clinical BL tissues. In vitro, Raji cells synthesized IL-4, IL-6, IL-10 and IL-13 to induce CD163, CD204 and B7-H1 expression in co-cultured macrophages, which in turn promoted Raji cell proliferation and invasion. Interestingly, antifungal agent amphotericin B not only inhibited STAT6 phosphorylation to suppress the M2 polarization of macrophages, but also promoted CD3+ T cell proliferation by regulating B7-H1 protein expression in macrophages. Conclusion: Amphotericin B might represent a novel immunotherapeutic approach to treat patients with BL.

Background: The purpose of the current study was to evaluate the efficacy and safety of a dose increased weekly Bortezomib (Bor) based combination therapy in multiple myeloma (MM) patients.Results: The overall response rate (ORR) in the modified Bor group was 76.6%, composed of 40% complete response (CR), 3.3% very good partial response (VGPR) and 33.3% partial response (PR).The ORR was 82.3%, with 26.5% CR, 5.9% VGPR and 50% PR in control.A subgroup analysis showed both groups had equal efficacy in newly diagnosed MM patients ( P = 1.000).The median progression free survival was 16 (11.7-20.3)months for the modified Bor group and 12 (10.5-13.5)months for the control (P = 0.503), and the median overall survival was 36 (9.4-62.6)vs 28 (21.6-34.4)months (P = 0.759).The incidences of AEs were similar except grade 1-4 peripheral neuropathy (PN) rate was 10% in modified regime group and 32.4% in control (P = 0.038).Materials and Methods: This was a monocentric, prospective, non-randomized, phase IV, non-inferiority trial.Thirty MM patients were treated with modified Borbased combination therapy (Bor 1.6 mg/m 2 on day 1, 8), with 34 MM patients on conventional Bor-based combination therapy (1.3 mg/m 2 on day 1, 4, 8, 11) as control.The responses and adverse events (AEs) were compared.Conclusions: The increased-dose weekly Bor-based combination therapies were not inferior to conventional ones in terms of response and survival benefit, but showed lower rate of peripheral neuropathy (PN).

The subcutaneous soft tissue of the forehead is a rare anatomic site for Hodgkin lymphoma (HL), and no such case has previously been reported in the literature, to the best of our knowledge. HLs commonly present in the nodal regions in the majority of patients, rarely occurring in extranodal sites, whereas primary extranodal lymphoma is less common and is more typical in cases of non-HL. The present study reports a novel case of extranodal head and neck classical HL (cHL), initially diagnosed as frontal fibroma. The present study describes an unusual case of subcutaneous soft tissue involvement of HL, aiming to enhance current levels of awareness for patients with extranodal symptoms. A 25-year-old male, who inadvertently detected a hard painless mass above the right superciliary arch 2 months prior to admission in April 2013 was eventually diagnosed with mixed cellularity cHL. Subsequent to six cycles of doxorubicin (Adriamycin), bleomycin, vindesine and dacarbazine chemotherapy, followed by four cycles of ifosfamide, gemcitabine, vinorelbine and prednisone chemotherapy, a satisfactory curative effect was obtained. In conclusion, it is proposed that lymphoma should be considered in the differential diagnosis of a mass involving the subcutaneous soft tissue.

>多发性骨髓瘤（multiple myeloma,MM）是中老年人群常见的血液肿瘤之一,近年来MM的基础及临床研究取得较大进展,不少新药的开发应用提高了患者疗效,改善了患者生存。其中硼替佐米临床应用后取得巨大成功,但也存在周围神经病变、并发带状疱疹等不良反应 [1-2] 。在本研究中我们通过调整给药频率及剂量、对以硼替佐米为基础的联合化疗方案进行改良,观察其对MM患者疗效及不良反应的影响,探讨硼替佐米应用的最佳方案和剂量,希望在疗效、不良反应间取得新的平衡。