A 42-year-old male with relapsed/refractory B-acute lymphoblastic leukemia underwent CD19-directed CAR-T cell therapy.Day +30 marrow evaluation demonstrated Minimal residual disease (MRD)-negative complete remission (CR) by multicolor flow cytometry.Peripheral blood counts at Day +30 showed hemoglobin 106 g/L, TLC 5.4 10/L, ANC 1.9 10/L, ALC 0.21 10/L, and platelets 113 10/L.Notably, the absolute monocyte count was markedly elevated at 3.24 10/L; morphological review confirmed that these cells represented circulating anti-CD19 CAR-T cells rather than true monocytes.The CAR-T cells appeared as large, irregular, monocyte-like forms with blastoid nuclei, loose chromatin, inconspicuous nucleoli, and abundant light blue cytoplasm (Figure 1 aj) 1.The atypical cells demonstrated features similar to those previously described in circulating activated CAR T cells.Although flow cytometric confirmation was not performed, the morphological features and temporal association with CAR T-cell infusion strongly suggest these atypical cells represent circulating CAR T cells.Circulating atypical cells may represent blasts or reactive atypical lymphocytes associated with viral infection.However, demonstration of MRD-negative CR in the bone marrow, together with the absence of fever or constitutional symptoms, excludes disease persistence and active infection.Given that the patient achieved MRDnegative CR, the atypical cells observed on peripheral smear are most consistent with circulating CAR T cells.These striking cytomorphologic features highlight the dynamic immunologic activity following CAR-T therapy and emphasize the importance of careful peripheral smear evaluation to correctly identify therapeutic cellular populations during post-infusion monitoring 2.
Kazi et al. (Wed,) studied this question.