CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.
Metastatic carcinoma of bone marrow (MCBM) tends to present with atypical symptoms and can be easily misdiagnosed or miss diagnosed. This study was conducted to investigate the clinical-pathological and hematological characteristics of MCBM patients in order to develop strategies for early detection, staging, treatment selection and prognosis predicting. We retrospectively analyzed 45 patients with MCBM diagnosed by bone marrow biopsy in our hospital during the past 7 years. The clinical symptoms, hemogram and myelogram features, Hematoxylin and eosin staining and immunohistochemistry staining of bone marrow biopsies, location of primary carcinoma and corresponding treatment of the 45 MCBM patients were analyzed in this study. In total, 35 (77.9%) of all patients presented pains including bone pain (73.3%) as the main manifestation, and 37 (82.2%) patients had anemia. Metastatic cancer cells were found in only 22 patients (48.9%) upon bone marrow smear examination, but in all 45 patients by bone marrow biopsy. The bone marrow of 18 (40.0%) patients was dry extraction. Distribution of metastatic carcinoma was diffuse in 20 (44.4%) patients and multi-focal in 25 (55.6%) patients, complicated with myelofibrosis in 34 (75.6%) patients. For bone marrow biopsy immunohistochemistry, 97.8% of the patients were CD45-negative, while 75.6% of the patients were Cytokeratin-positive. There were 30 patients (66.7%) identified with primary malignancies. The overall survival (OS) of 1 year for MCBM patients was 6.7%. There was a trend that patients with cancer of known primary obtained better prognosis according to the survival curve, but the finding was not statistically significant with Log-rank P = .160. Complete MICM-P plays a significant role in early diagnosis of MCBM. Bone marrow biopsy combined with immunohistochemistry is an underappreciated method for the diagnosis of MCBM, which should be taken as part of regular tests as well as bone marrow smear. Understanding the clinicalpathological and hematological characteristics of MCBM and conducting bone marrow biopsy in time are of great significance for early detection and treatment selection.Abbreviations: CUP = cancer of unknown primary, IHC = immunohistochemistry, MCBM = metastatic carcinoma of bone marrow, MICM-P = morphology immunology cytogenetics molecular biology-pathology, OS = overall survival.
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