Purpose: Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner.Experimental Design: MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models.Results: MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019-as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P < 0.005) but most mice receiving CTL019 monotherapy eventually relapsed. Therefore, we added ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 þ ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P < 0.05).Conclusions: Combining CTL019 with ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma.

Background: miR-21 is overexpressed in many human cancers, including glioblastoma. Results: Insulin-like growth factor (IGF)-binding protein-3 (IGFBP3) is a novel miR-21 target gene and inhibits gliomagenesis in vitro and in vivo. Conclusion: miR-21 down-regulates IGFBP3, which acts as a tumor suppressor in human glioblastoma. Significance: IGFBP3 may have promise as a therapeutic target and prognostic marker for glioblastoma.

Adult T-cell leukemia/lymphoma is a rare mature CD4+ T-cell neoplasm caused by the retrovirus human T-lymphotrophic virus type 1. At present there are approximately 20 million people infected globally with this virus, and most of these individuals belong to the endemic areas in southern Japan, Africa, the Caribbean basin, and Latin America. In the United States, it is usually seen in immigrants from these endemic regions. Adult T-cell leukemia/lymphoma predominantly affects the adult population and is rare in children. Adult T-cell leukemia/lymphoma has 4 subtypes: acute, lymphomatous, chronic, and smoldering. Clinically, the first 2 variants are classified as aggressive, and the latter two are classified as indolent. Given the rare occurrence and diagnostic challenges associated with adult T-cell leukemia/lymphoma, this review will highlight its salient features to aid in recognition of this entity and perform a comprehensive diagnostic workup.

Intravascular B-cell lymphoma (IVBCL) is a rare and aggressive subtype of extranodal diffuse large B-cell lymphomas. First described by Pflegrand and Tappeiner 1 in 1959 as "angioendotheliomatosis proliferans systemisata," it is characterized by preferential growth of neoplastic lymphoma cells within the lumina of small blood vessels, particularly capillaries. Despite the 50 years that have passed since the first description of this syndrome, our understanding about its pathophysiology is still limited, and the syndrome continues to be a diagnostic and therapeutic challenge for practicing hematologists and oncologists. In this article, we describe an unusual case of IVBCL in a patient who presented with neurologic symptoms, hemolytic anemia, and synchronous carcinoma. Case ReportA previously healthy 47-year-old African American male presented with slurred speech, left-sided facial droop, and upperextremity jerky movements. A neurologic examination showed left, upper motor neuron facial nerve palsy. The laboratory workup was significant for mild leucocytosis with a WBC count of 15 ϫ 10 9 /L with a normal hemoglobin and platelet count. Magnetic resonance imaging (MRI) of the brain showed multiple small bright lesions mainly in the right cerebral hemisphere associated with vasogenic edema. An embolic or vascular phenomenon was favored in the differential diagnosis. Spinal fluid analysis did not reveal neoplastic cells. Computed tomography (CT) of the chest, abdomen and pelvis showed bilateral adrenal lesions, and positron emission tomography/CT showed hypermetabolic disease only in bilateral adrenal glands. A core-needle biopsy of the left adrenal lesion revealed a poorly differentiated epithelial neoplasm. Cytokeratin was the only stain that was positive of the multiple stains tested on the specimen. Because of continued confusion regarding the etiology of brain lesions (metastatic disease v ischemia), a brain biopsy was recommended, which the patient declined. While in the hospital, the patient had an acute decline in hemoglobin to 6.5 g/dL. The anemia workup revealed Coombs-positive hemolytic anemia. An esophagogastroduodenoscopy and colonoscopy were negative for malignant lesions. Prednisone 1 mg/kg was started, and a rapid improvement in hemoglobin was seen in the next several days. The patient left the hospital against medical advice and was seen in a clinic with a lag period of 2 months. The patient was completely asymptomatic at that point, and steroids were tapered off. Restaging CT scans of the chest, abdomen, and pelvis showed interval improvement in the size of adrenal lesions. MRI of the brain revealed old ischemic changes but no evidence of a discrete metastatic lesion.The patient remained asymptomatic for the next few months until he started having vague abdominal discomfort. Repeat-staging studies showed an interval increase in the size of adrenal lesions. While D I A G N O S I S I N O N C O L O G Y V O L U M E 3 0 ⅐ N U M B E R 1 5 ⅐ M A Y 2 0 2 0 1 2 e144