ALBERT

Description: Backgroud: Autologous hematopoietic stem cell transplantation (ASCT) is widely recommended for relapsed or refractory lymphoma as an important second-line salvage therapy. Post-transplant relapse is a main issue due to its lacking of the graft versus tumor effects with routine ASCT. Hereby we present a novel hybrid transplantation with autologous stem cells and matched unrelated cord blood cells for relapsed or refractory lymphoma. Method A total of 37 patients with relapsed or refractory lymphoma were enrolled from July 2013 to May 30, 2019 in the West China Hospital of Sichuan University. The autologous peripheral blood stem cells were collected and freezed. HLA matched cord blood cells were searched and provided by the Sichuan Cord Blood Bank. Autologous peripheral blood stem cell transplantation (APBSCT) were infused at day 0 and the selected cord blood cells were infused at day+1 with standard BEAM conditioning regimen. Result The gender distribution was 51.4% female and 48.6% male.The Median age was 37 years old (16-65 years old). The disease characteristics: relapsed or refractory HL 14 cases, relapsed or refractory DLBCL 9 cases, relapsed Burkitt lymphoma 1 case, HGBL with DHL 1 case, DEL 4 cases, Nos 2 cases, DLBCL with high IPI 3 cases. Advanced nasal NK/T cell lymphoma 2 cases, relapdsed EBV-LPD 1 case. The median number of CD34*106/kg for ASCT was 2.35 (1.32-4.58). The median number of total nucleated cord blood cells was 10.2*108 (6.13-17.9) and the CD34+ cord blood cells was 2.72*106 (1.08-5.2). HLA-identical related donor (6/6) was 10.81%, one-antigen-mismatched (5/6) was 72.98%, two-antigen-mismatched (4/6) was 16.21%. All patients were transplanted succesfully with neutrophil recovery of 11days (8-29) and platelet recovery of 14 days (10-120). An early transplanted syndrom with rash or fever were observed in 7 pts (18.9%), while a delayed neutropenia were observed in 5 pts (13.5%). All symptoms were relieved with prednisone therapy. 2 out of 10 pts examined showed sign of microchimerism at 1 month post transplant. With a median 28 months of follow-up (2-73 months), our hybrid transplantation for R/R lymphoma showed that the relapse-free surviaval (RFS) is 90.4% ,and the overall survival (OS) is 86.4%, which is improved remarkablly. The overall OS and RFS were significant different between complete remission (CR) and Non-CR before transplantation (p= 0.002 for OS; p= 0.015 for RFS), but there was no significant difference in the subgroups of HL and NHL. Conclusion This preliminary pilot study suggested that the hybrid stem cell transplantation with autologous stem cells and matched cord blood stem cells is effective and safe for the treatment of high risk lymphoma with limited controlable immuno reactions. Disclosures Zhang: the National Natural Science Foundation of China: Research Funding.

Description: Abstract 4243 [Background] Imatinib combined with intensive chemotherapy protocol markedly has markedly improved the prognosis of patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ALL), and has become the standard therapy for this disease. Based on experience from patients with chronic myelogenous leukemia in blast crisis or accelerated phase, this highly specific tyrosine kinase inhibitor was given 600mg or 800mg daily in most clinical trials. However, some pilot study and case report implied that either lower dose of imatinib or less intensive chemotherapy could also achieve a satisfying remission rate. We carried out this pilot study to testify whether a lower dose of imatinib and less intensive chemotherapy could generate similar outcome, especially for patient who are unwilling to or unsuitable for allogeneic hematopoietic stem cell transplantation. [Method] Thirty six patients with de novo Ph+ALL were enrolled between Dec-2008 and Dec-2010. All patients received imatinib 400mg daily, vindesine 4 mg weekly and dexamethasone 10 mg/m2/day for 4 days per week as induction therapy. After complete remission, these patients received 3 courses chemotherapy of protocols adapted from China Acute Lymphocytic Leukemia Group (CALLG) as intensification. Those who were unwilling to receive or unsuitable for allo-HSCT received maintenance therapy with imatinib 400mg daily with chemotherapy by vindesine 4 mg on D1 and D11, dexamethasone 10mg/m2/day on D1-5 and D11-15 with or without interferon-α 3 million unit every other day. Patients over 55 year old skipped the intensification therapy. The maintenance chemotherapy was given once a month in the first year, once per 2 months in the second year, and once per 3 months in the third year. Sixteen cycles of intrathecal chemotherapy with cytarabine and dexamethasone +/− methotrexate was scheduled for central nervous system leukemia (CNSL) prophylaxis. [Result] Thirty six patients were enrolled, and the median age of this group of patients was 33.5 years (shown in table 1). All but one patients (97.2%) achieved complete remission after 4 weeks of induction therapy. One patient was loss of follow-up and one patient quit from this study because of severe hepatic dysfunction thought to be caused by imatinib. Three patients (8.3%) died of infections (pneumonia or sepsis) within intensification cycles. Three (8.3%) patients received allo-HSCT either from a sibling or an unrelated donor at CR1 after 3–4 courses of intensification therapy. The median time of follow-up was 8 months. The median overall survival was were 22.1 (shown in figure 1A.). For patients who received imatinib and chemotherapy only, the median overall survival was 20.4 months (shown in figure 1B). Although there was no evidence for CNSL at diagnosis in all patient, four (11.1%) patients had CNS relapse and three died despite of regular CNSL prophylaxis. [Conclusion] In this pilot study, our data showed that imatinib combined with less intensive chemotherapy could also achieve a over 90% remission rate in patients with de novo Ph+ALL. With the short time of follow-up, the long term effect of this strategy on survival and relapse can not determined yet, and a prospective randomized study is warranted. With reduced chemotherapy intensity, a more intensive protocol for CNS prophylaxis or new generation of TKI (e.g. dasatinib) with higher blood-brain barrier permeability may be considered. Disclosures: No relevant conflicts of interest to declare.

Description: Objective. Hemophagocytic lymphohistiocytosis (HLH), also known as Hemophagocytic Syndrome (HPS), is an increasingly recognized clinical syndrome that is characterized by extreme immune activation. HLH was first described as an inherited immune disorder in pediatrics, but it may also arise in adults as the result of persistent antigen stimulation due to infections, autoimmune disorders or malignancies. Early recognition of HLH and appropriate treatment are critically important. For the pediatric patients, the Histiocyte Society Study Group for HLH has developed the HLH-94 and HLH-2004 treatment protocols, but there is no such guideline or consensus for adult HLH. Although there were increasing amount of clinical studies in adult HLH, the majority of them just described the etiologies and clinical profiles, and failed to analyze the treatment effects on outcomes. Therefore, there is an urgent need for more clinical data focusing on treatment in adult HLH patients, in order to clarify optimal therapeutic regimens. Our study retrospectively analyzed the causes, treatment strategies, and relevant outcomes in 104 adult HLH patients in our institution, and with the goal of identifying more appropriate therapeutic strategies for adult HLH patients. Methods. After the approval of our protocol by local institutional Ethics Committee, the medical records of 104 consecutive patients with adult onset HLH in West China Hospital from June 2008 to February 2016 were reviewed. The diagnosis was re-confirmed according to HLH-04 criteria, and demographic data, clinical profiles, treatments and outcomes were collected and analyzed. The latest follow-up visit occurred on 1st July 2016. The different therapeutic effects on prognosis were discussed based on the endpoints which were defined as short-term (30 days) and long-term (last follow-up date) survival rates. Statistical analysis was performed on SAS 9.4 software, and was involved in Log-rank test in univariate analysis and Cox proportional hazard regression model in multivariate analysis. All p values were two-sided and p

Description: Background The demethylating agent decitabine (DCA) had been employed in the treatment of acute myeloid leukemia (AML) as epigenetic therapy. A phase 3 trial for older patients (pts) with newly diagnosed AML had clearly demonstrated that DAC alone was more effective than ‘treatment choice’. However, outcomes are poorer in refractory AML with DAC alone or chemotherapy alone. Since combine index of DAC and Ara-C had been reported in preclinical study, the efficacy and safety of DAC combined with chemotherapy for pts with refractory AML were investigated in this pilot phase 1 clinical study. Patients A total of 23 pts (8 female and 15 male) with AML were enrolled from Jan 4 2012 to June 30 2013. According to World Health Organization (WHO) classification criteria, 2 pts were diagnosed as AML-M1, 6 were AML-M2, 4 were AML-M4, 7 were AML-M5 and 4 were AML-M6, among whom 6 pts were with overt myelodysplastic syndrome (MDS) history. Median age was 61 years (range, 36-78). The Eastern Cooperative Oncology Group (ECOG) score was 1 in 5 pts, 2 in 13 pts and 3 in 5 pts. Median courses of disease was 9 months (range, 3 months to over 4 years). Cytogenetics at diagnosis according to National Comprehensive Cancer Network (NCCN) guideline was poor-risk in 7 pts, not poor-risk in 12 pts and without examination of cytogenetic abnormality in 4 pts. 19 pts had received at least 2 standard courses of chemotherapy and failed to achieve complete remission (CR), 4 pts could not tolerate standard chemotherapy. Methods At the beginning, 4 pts were given DAC 15 mg/m2/day intravenous (IV) over 90 minutes from days 1 to 5, and chemotherapy was given 48 hours after the first dose of DAC. Two pts were enrolled into DAC with standard DA regimen, and another two into DAC with AA (aclacinomycin 10 mg/d IV days 3 to 6 and Ara-C 10mg/m2 ih bid days 3 to 9). As DAC with DA regimen was poorly tolerated, then the other 19 pts were enrolled into 2 schedules of DAC plus AA. Schedule 1(12Pts) was DAC 15 mg/m2/day IV 90 minutes qd, days 1 to 5; schedule 2(7Pts) was DAC 15 mg/m2 IV 90 minutes bid, days 1 to 3(According to a special situation in China, 50mg DCA was divided into two equal amount, from which the needed amount was used separately in a interval of 4 hours) The therapy were given at least 2 courses, and continued until pts achieved CR. During treatment with DAC and chemotherapy, pts were given best available support care including blood component transfusion, preventing infection and granulocyte colony-stimulating factor (G-CSF) subcutaneous injection. Results Among the 23 pts, 11 (47.8%) achieved CR or bone marrow remission without platelet recovered(CRp), 3 achieved partial remission (PR). The overall response rate (ORR) was 60.9%. Up to now, 16 pts were still alive, 6 were dead, and one lost follow-up. For the 6 death, 4 were caused by disease progression, one by severe infection, and one in CR condition died from food obstruction in the laryngeal which was a very rare situation. The half-year overall survival rate (OS) was 64.7%. For pts who achieved CR/CRp, the half-year OS was 88.9%. 10 pts (43.5%) were with 3 to 4 grade of myelosuppression; 16 pts (69.6%) developed infection. There was no statistically significant difference in efficacy (62.5% VS 60%) and safety between the two schedules of DAC, and also no statistically significant difference in subgroups, in terms of WHO classification, age (distinguished by age of 60), pre-treatment courses, ECOG and NCCN cytogenetics. Conclusion DAC combined with AA (aclacinomycin and Ara-C) was efficient and tolerable for refractory AML pts, and the advantage of the 2 DAC schedules should be evaluated by further study. Results of subgroup analysis indicated that DAC combined with AA could overcome poor prognosis factors such as WHO classification, elder age, pre-treatment courses, ECOG score and poor-risk cytogenetic abnormalities. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3714 Background: The non-GCB subtype of diffuse large B-cell lymphoma(DLBCL) has inferior response to rituximab based chemothrapy. Recent reports show a constitutional expression of NF-κB pathway in non-GCB subtype of DLBCL. Bortezomib, as proteasome inhibitor, has been shown a promising new agent for the treatment of DLBCL. As how the efficacy, doses and protocol of Bortezomib need to be clarified. Objective: This trial is a pilot multicenter clinical study to evaluate the efficacy and safety of an escalated dose of bortezomib based chemotherapy for the treatment of patients with relapsed or refractory non-GCB subtype of DLBCL. Patients and Materials: A total 24 pts with DLBCL were enrolled in 4 different medical centers. According to Hans' Tissue Microarray (TMA) Classification, 23 pts were diagnosed as non-GCB subtype, and 1 patient have not done the test. 16 pts had relapsed or refractory disease, while 8 pts had fail response to the first line treatment. All the patients had received Rituximab based chemotherapy previously. There were 16 male and 8 female. The patient age ranged from 19 to 73, of which the median age was 55. Methods: All patients were given bortezomib 2.0mg/m2, day 1, I.V. (intravenous injection 12 hours before chemotherapy), 5 pts were given additional dose of 0.7 mg/m2, I.V., at day 8. The combination protocols include: Bortezomib(V)+ICE(G) 13 pts; Bortezomib(V)+HyperCVAD 7 pts; Bortezomib(V)+EPOCH 3 pts; Bortezomib(V)+DHAP 1 pts. The patients were given 1 to 5.courses differently. Results: The follow-up time were 2 to18 months, with a median time of 8 months. Of 24 pts, 21 evaluable pts received more than 2 courses of therapy: 7 pts achieved complete remission (CR 33.3%), 9 pts achieved partial remission (PR 42.8%), 5 pts had no response (NR 23.8%), The overall response rate (ORR) was 76.1%. Of 16 responsive pts, the PFS were 2 to 18 months; the average PFS was 7.6 months and median PFS was 7.5 months. Up to now, 13 pts were still alive, and 7 pts were dead, and 1 pts lost follow-up. Of 7 death, 5 were caused by disease progression with 4 pts of central nervous infiltrates, 2 were caused by severe infections. The one year overall survival rate (OS) was 65%. Of all the 24 pts, 10 pts had 3 to 4 grade of myelosuppression; 1 case with severe pulmonary infection;1 case with septicemia; 1 case with skin and soft tissue infection; 1 case with fungus infection; 3 cases with herpes zoster infection; 2 cases with skin rashes; 2 cases with hypotension, 1 case with hepatic dysfunction; 1 case with neuralgia. Conclusion: Our study showed that the escalated dose of bortezomib based chemotherapy had promising response for the treatment of relapsed or refractory non-GCB originated DLBCL. Bortezomib at a single dose of 2.0mg/m2 was safe and tolerable. No acute toxicity or vital adverse events were observed. The relapse of disease in central nervous system as well as infections were relatively common and might need further study. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Peritoneal cavity cells are a group of isolated cells with unique functions, they have great anti-inflammatory, immune modulation and tissue recovering abilities. Several studies have independently reported the therapeutic function of peritoneal cavity cells on mice models with ulcerative colitis or other inflammatory bowel diseases. In the current study, we further investigated the effect of peritoneal cells on treatment of GVHD on mice models. Methods: We selected a dose of 7.0Gy of TBI for BABL/c mice. And 4 hours after TBI, BABL/c mice were infused with 5*106BMCs cells or 1*106spleen cells of C57BL/6 mice through tail veins to construct MHC mismatched myeloablative allogeneic hematopoietic stem cell transplantation model. The mice were randomly separated into two groups, which were infused with normal saline and 5* 106peritoneal cavity cells on day 0, 3, and 5. Survival time, weight changes, GVHD score were evaluated. Peritoneal cavity cells of GFP C57BL/6 transgenic mice were injected into mice recipients at day 5 after transplantation to observe the distribution of GFP positive cells in mice recipients. Flow cytometry was used to test proportion of CD4/CD8 cells and proportions of effector T cells and Naïve T cells in CD4 and CD8 cells of spleen and bone marrow in BMT group and peritoneal cavity cells group at different time points after transplantation. TNF-α, IFN-γ, IL-2, IL-17, IL-15, IL-4, IL-10 and TGF-β in plasma were studied with the method of Luminex at different time points in two groups. Expression of IL-10 and TGF-β in colons, intestines, and livers were assessed with immunofluorescence staining. Results: Mice in peritoneal cavity cells group had significant longer survival time and rapidly weight loss recover. Mice in peritoneal group had better performance in activity, unhairing, and skin changes as well. Counts of blood cells and chimeric status at day 7, 14, 21, 28 after transplantation showed that blood count recovered and stable chimerism in both groups. Small living animal imaging technology found that peritoneal cavity cells concentrate in colons and intestines after injection of GFP C57BL/6 transgenic mice peritoneal cavity cells. Fluorescence microscope showed that large amounts of green fluorocyte distributed mostly in colons and intestines, with few in liver. Flow cytometry proved that many GFP positive cells in intestines and colons (30%, and 15%, respectively), and a few in livers and lungs (approximately 5%), while negative in control group. We analyzed the lymphocyte subsets of spleen and bone marrow in two groups with flow cytometry and found that peritoneal cells treatment could increase the proportion of CD4 cells and decrease CD8 cells. In CD4 subsets, proportion of effective T cell decreased apparently 3 weeks after transplantation, and count of naïve T cells increased, which is not found in BMT group. Flow cytometry also showed that proportion of Treg cells, Th2 cells and NK cells were significantly higher in peritoneal cavity cells group, while proportion of Th1 cells were lower. TGF-β, IL-10 and IL-4 were significantly higher in peritoneal cavity cell treatment group, while TNF-α, IFN-γ, IL-15, IL-2 were lower. Immunofluorescence staining also showed that TGF-β and IL-10 were strongly expressed in colons and intestines, but not in BMT group. Conclusion: These results demonstrate that peritoneal cavity cells could ameliorate graft-versus-host disease of mice after MHC mismatched bone marrow transplantation. Survival time was prolonged, and weight loss, GVHD score, and pathologic injuries to tissues improved after infusion of 5* 106peritoneal cavity cells into BMT mice. Peritoneal cavity cells injected to BMT mice concentrate mainly in colons and intestines, which functioned as anti-inflammation and tissue repairing cells. These cells could modulate differentiation of T lymphocytes of mice recipients, decrease proportion of CD8 cells and increase CD4 cells, increase proportion of Tn cells and decrease that of Te cells in CD4 subsets, and increase proportion of Tregs, Th2 and NK cells and decrease that of Th1 cells. Peritoneal cavity cells could influence levels of cytokines by increasing anti-inflammatory factors including TGF-β, IL-10, IL-4, and significantly decreasing inflammatory factors like IFN-γ, TNF-α, and IL-15. Figure. Figure. Disclosures Liu: West China Hospital of Sichuan University: Employment.