ALBERT

Description: 【Introduction】Relapsed and refractory idiopathic Multicentric Castleman's disease (R/R iMCD) is a challenge for hematologists with poor prognosis. In the current study, we aimed to investigate the efficacy and safety of BCD regimen (bortezomib, cyclophosphamide, dexamethasone) in R/R iMCD patients. 【Methods】From 2017 to 2020, R/R iMCD patients who met the diagnostic criteria (Blood. 2017;129(12):1646-1657) were enrolled from Peking Union Medical College Hospital and Peking University First Hospital. BCD regimen (botezomib 1.3mg/m2 weekly, cyclophosphamide 300mg/m2 weekly, dexamethasone 40mg weekly out of a 28-day cycle) was administered for 9 cycles; after 9 cycles of BCD treatment, BD regimen (botezomib 1.3mg/m2 twice a week, dexamethasone 20mg twice a week) was used as maintenance for the next 1 year. Treatment was discontinued after 1 year of maintenance or until treatment failure which was defined as death or progression of disease. Treatment responses were evaluated according to the treatment guidelines published recently (Blood. 2018;132(20):2115-2124). Biochemical, lymph node and symptomatic responses were evaluated which all contributed to the assessment of overall response. An overall CR (complete response) requires a complete biochemical, lymph node, and symptomatic response. An overall PR (partial response) requires nothing less than a PR across all categories, but not meeting criteria for CR. Overall SD (stable disease) requires no PD in any of the categories and not meeting the criteria for CR or PR. An overall PD (progression of disease) occurs when any category has a PD. 【Results】Data from 20 patients who were followed for at least 6 months were analyzed. The median age was 42 years (range 22-65 years), with a male: female ratio of 1.5:1. Six patients were defined as 'refractory' and fourteen patients were classified as 'relapsed'. ALL patients (n=20) received BCD regimen and was followed every three months. As for biochemical response, 75.0% (n=15) achieved PR; 15.0% (n=3) were assessed as SD; 10% (n=2) were evaluated as PD. As for lymph node response, 5% (n=1) achieved CR and 75.0% (n=15) achieved PR; 10% (n=2) had SD while 10% (n=2) suffered from PD. As for symptomatic response, 85% (n=17) had PR (45%) or CR (40%); 15% (n=3) experienced PD. After incorporation of all the above evaluation results, 75.0% (n=15) patients achieved overall treatment responses (all were overall PR); 10% (n=2) patients were evaluated as overall SD; 15% (n=3) patients suffered from overall PD and were evaluated as treatment failure. As for safety issues, no patient suffered from Grade 3 or above adverse events and no patient died from treatment-related toxicity. With a median follow-up of 22 months (range 8-38), 40.0% (n=8) patients experienced disease of progression and two of them died from progression of iMCD. The estimated 1-year progression-free survival (PFS) and overall survival (OS) were 85.0% and 90.0% respectively (Fig 1). 【Conclusions】BCD regimen is an effective and safe treatment option for relapsed/refractory iMCD patients. Fig 1. Kaplan-Meier survival analyses of relapsed/refractory iMCD patients receiving BCD regimen showing the overall survival and progression-free survival. Figure 1 Disclosures No relevant conflicts of interest to declare.

Description: Backgroud: Waldenström macroglobulinemia (WM) is an uncommon indolent B cell non-Hodgkin lymphoma, which has heterogeneous clinical presentations and indications for treatment. Mostly the choice of first-line therapy is based on the individual patient's characteristic and indications for treatment. In China, previous studies on WM are mostly from single-center with small sample size, limiting the information available on treatment and outcome patterns. To address this knowledge gap, we present data from an analysis based on a nationwide multicenter registry with 17-years follow-up. Our study focuses on the clinical presentation, first-line therapies, as well as outcome and prognosis of WM in China. Methods: Patients diagnosed with WM between January 2003 and December 2019 at 35 academic hospitals in China, which have been entered in the database of the China Waldenström macroglobulinemia Registration (CWMG), were included in this retrospective study. Data including baseline clinical features, symptoms requiring treatment, treatment and survival were collected. The overall survival (OS) was defined as the duration from the diagnosis of WM to the date of death or last follow-up. Results: Overall 1141 patients were enrolled, 829 patients were male (72.7%), with a male-to-female ratio of 2.7:1. The median age at diagnosis was 64 years (range, 29-89 years), which 472 patients (41.4%) were older than 65 years, and 126 patients (11.0%) were older than 75 years. The patients' family histories included 6 WM and 4 other lymphoproliferative disorders. Symptoms leading to treatment initiation including anemia in 828 patients (72.6%), organomegaly in 441 patients (38.7%), thrombocytopenia in 302 (26.5%), neutropenia in 246 (21.6%), constitutional symptoms in 203 (17.8%), Bing-Neel syndrome in 13 (1.1%), IgM-related symptoms in including secondary amyloidosis in 32 (2.8%), secondary autoimmune hemolysis in 25 (2.2%), peripheral neuropathy in 23 (2.0%), secondary cold agglutinin disease in 21 (1.8%), secondary cryoglobulinemia in 11 (1.0%). At the time of diagnosis, 1125 patients had full information for IPSS-WM risk stratification. Among them, 194 patients (17.2%) were classified as low risk, 436 patients (38.8%) were intermediate risk, and 495 patients (44.0%) were high risk. Overall, 734 patients had documented treatment information. 75 patients (10.2%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, and 395 (53.8%) receive other combination regimens (Figure 1). The most frequently used monotherapy was chlorambucil (3.1%), followed by ibrutinib (2.9%) and rituximab (2.5%). Rituximab, cyclophosphamide and dexamethasone or prednisone (DRC or RCP) were the most frequently used chemoimmunotherapy (10.8%). Followed by rituximab plus cyclophosphasmide, vincristine/vincristine and prednisone/prednisolone (R-COP) (6.8%), R-COP plus doxorubicin/epirubicin (R-CHOP) (6.1%), rituximab plus fludarabine, cyclophosphamide (R-FC) (4.5%), rituximab plus bortezomib based regimen (3.5%). Other combination regimens including bortezomib based regimen (18.6%), FC (10.6%), CHOP (9.3%), immunomodulatory drug based regimen (5.7%), chlorambucil plus prednisone (4.4%). After a median of 23 months (range 1-201 months) follow-up, 123 patients died. The estimated 5-year OS was 74.9%. Median OS were similar among patients who received monotherapy, chemoimmunotherapy or other combination regimens. To evaluate the prognostic factors of OS using multivariate Cox regression model, age 〉 65 years old (P=0.011, HR 0.622, 95% CI 0.431-0.898), platelet 〈 100×109/L (P=0.006, HR 0.570, 95% CI 0.381-0.853), serum albumin

Description: Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). As a complex immunopathology, aGVHD depends on the recognition of host antigens by donor T cells and induces augmented response of alloreactive T cells. Despite considerable achievements in the treatment of aGVHD, it remains a major clinical problem for the patients undergoing allo-HSCT. Therefore, it is necessary to further illustrate new mechanisms and develop novel therapeutic strategies of aGVHD. Previously we reported LYG1 (Lysozyme G-like 1) as a novel classical secretory protein promoted antitumor function of T cell. In this study, the role of LYG1 in aGVHD was investigated. Firstly, we examined whether LYG1 affected the alloreactivity of CD4+ T cells in vitro by MLR assay and discovered that LYG1 deficiency reduced the activation of CD4+ T cells and Th1 ratio, but increased Treg ratio. Then we confirmed these observations using a major MHC mismatched aGVHD model by transferring T cells sorting from WT B6 or Lyg1-/- mice with bone marrow cells from WT B6 mice into lethally irradiated BALB/c mice. The alloreactive CD4+ T cells and the proportions of Th1 cells decreased whereas the proportions of Treg cells increased in spleens and livers in mice receiving Lyg1-/- T cells. LYG1-deficient T cells attenuated aGVHD severity, inhibited the expression of CXCL9 and CXCL10 and restrained CD4+ T cells infiltrating in livers. Furthermore, administration of recombinant LYG1 protein intraperitoneally aggravated aGVHD by promoting IFN-γ production. More importantly, LYG1 deficiency did not affect GVT (graft-versus-tumor) effects. In summary, we demonstrate LYG1 regulates aGVHD via modulating the alloreactivity of CD4+ T cells and differentiation of Th1/Treg cells. Our study indicates that LYG1 may be a novel target in aGVHD by mitigating aGVHD without impairing GVT function. The therapeutic effect of targeting LYG1 is required in future investigations. Funding This study was supported by grant from The National Natural Science Foundation of China (NSFC) (Grant Number 81600144) and grant from Research Foundation of Peking University First Hospital. Disclosures No relevant conflicts of interest to declare.