The COVID‐19 pandemic potentially makes treatment of acute leukaemia more difficult. Most induction chemotherapy regimens for acute leukaemia lead to extended periods of cytopaenia and immunosuppression rendering patients vulnerable to opportunistic infections. As with many aspects of SARS‐CoV‐2, there is no universally accepted way of treating patients who present with acute leukaemia and associated infection.
We report a 2‐year‐old female with a subcutaneous tumor who was initially misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the diagnosis of acute lymphoblastic leukemia was established. This necessitated further analysis of the subcutaneous tumor. The tissue was positive for immature B‐cell markers and an immunoglobulin heavy chain gene rearrangement, which confirmed the final diagnosis of common type acute lymphoblastic leukemia with bulk extramedullary disease. The patient was treated with chemotherapy and was in remission 30 months after the diagnosis. Pediatr Blood Cancer 2010;54:606–609. © 2009 Wiley‐Liss, Inc.
Background: CAR T cells targeting CD19 are approved for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), failing two or more prior therapies. The central nervous system (CNS) is a known sanctuary site of ALL. Despite observations of CAR T-cells trafficking to the CNS in patients, most clinical trials excluded patients with active CNS leukemia, partially for concerns of neurotoxicity. Methods: We conducted an international retrospective study of patients who were referred to CAR T-cell therapy for relapsed ALL with CNS involvement. Results: We reviewed data of 27 patients (16 males and 11 females) from 8 centers who were treated with CD19 CAR T-cells for ALL relapse involving the CNS. Fifteen patients had a prior bone marrow transplantation, and in seven total body irradiation was given. Four additional patients received previous cranial radiation. At time of CAR T-cell order or clinical trial inclusion, ten patients had an isolated CNS relapse, and 17 had a combined CNS and marrow relapse. The median number of cells in the CSF of patients at enrollment was 65 (range 0-5670), and 16 of 21 patients who had imaging performed showed leukemia-associated changes in brain MRI. All patients received bridging chemotherapy between enrolment and lymphodepletion, including intrathecal chemotherapy alone or in combination with systemic chemotherapy and/or radiation. At lymphodepletion, 15 patients had cleared CNS disease while 12 had active CNS blasts or imaging lesions. Following lymphodepletion with fludarabine and cyclophosphamide, patients received 2nd-generation CAR T cells: 15 patients treated with a CD19-4-1BB CAR and 12 with a CD19-CD28 CAR. Cytokine release syndrome (CRS) occurred in 20 patients: 12 patients (100%) treated with CD19-CD28 CARs and 8 with CD19-4-1BB CARs (53%, p=0.006). Immune-effector cell neurotoxicity (ICANS) was diagnosed in 11 patients, 9 of 12 following CD28-based CARs, and 3 of 15 following 41BB-based CARs (p=0.004). Patients with active CNS-disease prior to lymphodepletion also had a higher rate of ICANS (75% vs 20%, p=0.004) but not of CRS. One patient died of grade 5 ICANS on day +7 following CD28-based CARs for an isolated CNS relapse. Twenty-four of 26 evaluable patients (92%) had a complete remission following CAR T-cells. Nine patients were further referred to an allogeneic transplant, all following CD28-based CARs. Overall, six patients had relapsed - in four relapse involved bone marrow, and in two the CNS. Conclusions: In this cohort of patients with active CNS disease treated with CD19 CAR T-cells, we report a high remission rate in previously heavily pre-treated patients. Toxicities are significant, and associated mostly with the costimulatory domain of the CAR (CD28>41BB) and the presence of active CNS disease at lymphodepletion. This may be informative when designing future clinical studies of CAR T cell therapy for patients with CNS manifestations of ALL. Disclosures Jacoby: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Lonza: Membership on an entity's Board of Directors or advisory committees. Ghorashian:Novartis: Honoraria; UCLB: Patents & Royalties; Amgen: Honoraria. De Moerloose:Novartis: Consultancy. Rossig:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. von Stackelberg:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, advisory committees and speakers bureau, Speakers Bureau. Bourquin:Servier: Other: Travel Support. OffLabel Disclosure: We describe the use of commercial and investigational CAR T-cell products
Background and progress in research Autologous Haematopoietic Stem Cell Transplant (AHSCT), also known as bone marrow transplant, is an experimental form of treatment that aims to reset, or 'reboot' the immune system to prevent the autoimmune attack on the central nervous system.
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