interphase-fluorescence-situ-hybridization-bone-marrow-smears

Interphase Fluorescence <em>in situ</em> Hybridization of Bone Marrow Smears of Multiple Myeloma

Fluorescence in situ hybridization (FISH) detection is an indispensable method in genetic risk stratification in multiple myeloma (MM), which is one of ...

zhongnan hospital of Wuhan University

CAR T cell therapy has shown dramatic clinical success in relapsed or refractory B-ALL and other hematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is strongly expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal blood cells. Moreover, T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide and without normal blood cells toxicity. We observed that our anti-CD99 CAR T cells showed robust cytotoxicity specifically against CD99+ T-ALL cell lines and primary tumor cells in vitro and significantly prolonged cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) models survival in vivo. Together, our results demonstrate that anti-CD99 CAR T cells could specifically recognize and efficiently eliminate CD99+ leukemia cells.

CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity.

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p < 0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p < 0.0001). In different subgroups grouped according to age, hemoglobin (HGB), creatinine, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age >65 years (p = 0.001), HGB < 100 g/L (p < 0.001), elevated LDH (p = 0.001), and Ca (p = 0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.

Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents.

 Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis.  From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM. TEC machine.  After apheresis, the median CEPP was 20.71% (IQR: 9.99-36.69%) and median PLT reduction rate was 25.87% (IQR: 21.78-36.23%). Further analysis showed that no significant difference was observed between PLT count with 800-1,000 × 10/L and > 1,000 × 10/L. The PLT counts significantly decreased ( < 0.001) after plateletpheresis, the red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB), and hematocrit (HCT) levels showed no significant differences before- or after- plateletpheresis. Multivariate analysis showed that female sex ( = 0.009) and HGB ( = 0.010) before apheresis were associated with CEPP. Female ( = 0.022), HCT ( = 0.001) and blood volume ( = 0.015) were associated with the PLT reduction rate. Furthermore, symptoms were relieved after apheresis in patients whose PLT count was 800-1,000 × 10/L accompanied with symptoms.  It is reasonable to perform plateletpheresis when the PLT count is over 800 × 10/L and patients are complicated by clinical symptoms such as dizziness, headache, somnolence, and stupor. Plateletpheresis is effective in removing PLTs especially in females with high HGB.

Article	Year
CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity. Journal of hematology & oncology\| PubMed ID: 34627328	2021
Evaluation of prognostic staging systems of multiple myeloma in the era of novel agents. Hematological oncology\| PubMed ID: 34860428	2022
Therapeutic Plateletpheresis in Patients With Thrombocytosis: Gender, Hemoglobin Before Apheresis Significantly Affect Collection Efficiency. Frontiers in medicine\| PubMed ID: 35004735	2021

Xiqin Tong

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