Diagnostic approach to the evaluation of myeloid malignancies following CAR T-cell therapy in B-cell acute lymphoblastic leukemia

• Published in: Journal for immunotherapy of cancer Vol. 8; no. 2; p. e001563
• Main Authors: Mo, George, Wang, Hao-Wei, Talleur, Aimee C, Shahani, Shilpa A, Yates, Bonnie, Shalabi, Haneen, Douvas, Michael G, Calvo, Katherine R, Shern, Jack F, Chaganti, Sridhar, Patrick, Katharine, Song, Young, Fry, Terry J, Wu, Xiaolin, Triplett, Brandon M, Khan, Javed, Gardner, Rebecca A, Shah, Nirali N
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.11.2020; BMJ Publishing Group
• Subjects: Antigens; Biopsy; Bone marrow; Cancer; Case Report; Cloning; Cytogenetics; Flow cytometry; Immunotherapy; Leukemia; Lymphocytes; Remission (Medicine); Sarcoma; Stem cell transplantation; chimeric antigen; adoptive; receptors; immunotherapy
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2020-001563

Immunotherapeutic strategies targeting B-cell acute lymphoblastic leukemia (B-ALL) effectively induce remission; however, disease recurrence remains a challenge. Due to the potential for antigen loss, antigen diminution, lineage switch or development of a secondary or treatment-related malignancy, the phenotype and manifestation of subsequent leukemia may be elusive. We report on two patients with multiply relapsed/refractory B-ALL who, following chimeric antigen receptor T-cell therapy, developed myeloid malignancies. In the first case, a myeloid sarcoma developed in a patient with a history of myelodysplastic syndrome. In the second case, two distinct events occurred. The first event represented a donor-derived myelodysplastic syndrome with monosomy 7 in a patient with a prior hematopoietic stem cell transplantation. This patient went on to present with lineage switch of her original B-ALL to ambiguous lineage T/myeloid acute leukemia. With the rapidly evolving field of novel immunotherapeutic strategies, evaluation of relapse and/or subsequent neoplasms is becoming increasingly more complex. By virtue of these uniquely complex cases, we provide a framework for the evaluation of relapse or evolution of a subsequent malignancy following antigen-targeted immunotherapy.