Anti-CD19 Chimeric Antigen Receptor T Cells Improve Responses to Chemotherapy-Refractory Mantle Cell Lymphoma: A Case Report
Authors: Chen Weihong , Du Xin , Luo Changru , Zhang Qiaoxia , Wang Mingjun 
Published: October 2019

Abstract
BACKGROUND: Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma(NHL), an aggressive lymphoma that does not respond well to chemotherapy. The patient has chemotherapy-refractory MCL. As the patient immunophenotype is CD19 positive, anti-CD19 Chimeric Antigen Receptor (CAR T 19) Cells are administered in order to treat his chemotherapy-refractory MCL.
CASE PRESENTATION: The MCL patient, who is male and 60 years of age, has been treated at Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University. Patient had been suffering from painless enlarged lymph nodes on neck, armpits and groin for two years when he was hospitalized in April 2015; he also suffered from abdominal pain since March 2015 and shortness of breath for 7 days. Physical examination: the painless enlarged lymph nodes on neck, armpits and groin from multiple bilateral, 1 × 1.5-4.5 × 5cm size. Right groin lymph node biopsy and immunohistochemistry showed NHL, B lymphocyte cell type, MCL. Bone marrow showed 7% of lymphoma cells. Immunophenotype showed positive expressions of CD5, CD19, CD20, CD23. PET/CT scan showed systemic lymph node with multiple nodules and massively increased images, with diffusion and radioactivity in the spleen having also increased. CT showed right pleural effusion a lot, hilar, chunks of retroperitoneal tumor, splenomegaly. Diagnosis was MCL IV of Group B, B lymphocyte cell type with right pleural effusion. We treated the patient with R-CHOP 4 cycles of chemotherapy from May 7, 2015. The result was poor. We infused autologous T cells transduced with a CAR T 19 cells retroviral vector with the chemotherapy-refractory MCL at doses of 6.0×10e8 CAR T 19 cells October, 2015. Patients were monitored for a response, any toxic effects, and the expansion and persistence of circulating CAR T 19 cells. After CAR T 19 cells were infused, the patient experienced chills, fever, shortness of breath, abdominal distension, abdominal pain, chest tightness, and heart palpitations for 9 days. The diagnosis was cytokine release syndrome. After the patient took an anti-IL-6R antibody, he began to recover. Enlarged lymph nodes got shrunken after being infused with CAR T19 cells for 7 days. The peripheral blood CD19 B lymphocytes cell is 0. The right pleural effusion gradually decreased. The lymphadenopathy was cured after 4 months of infusion, with pleural effusion disappearing after 5 months. Q-PCR was used to detect the amount of CAR T 19 cells, which stood at 1.68x10e6 copies/L after 6 months of infusion. After treatment with CAR T 19 cell therapy for 10 months, the patient's state is good.
CONCLUSIONS: Cancer immunotherapy as a method of cancer treatment is the most effective after conventional treatments such as radiotherapy, chemotherapy, and surgery. For CD19+ lymphoma, CD19 is a very favorable target, because the expression of CD19 is limited to B cells and not expressed in other tissues or cells. Currently, the efficacy of this treatment in treating MCL remains to be seen. Effects of chemotherapy on the patient's MCL is negligible, due to the fact that his lymph nodes and lymph tissue have become malignant. As a result we chose the CAR T19 cell therapy genetic engineering technique as a method of treatment, to which the patient has responded well.

Disclosures
No relevant conflicts of interest to declare.