Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 18;141(20):2460-2469.
doi: 10.1182/blood.2022017415.

How I treat cytopenias after CAR T-cell therapy

Tania Jain  1 , Timothy S Olson  2 , Frederick L Locke  3
Affiliations

How I treat cytopenias after CAR T-cell therapy

Tania Jain et al. Blood. .

Abstract

Increasing use of chimeric antigen receptor T-cell therapy (CAR-T) has unveiled diverse toxicities warranting specific recognition and management. Cytopenias occurring after CAR-T infusion invariably manifest early (<30 days), commonly are prolonged (30-90 days), and sometimes persist or occur late (>90 days). Variable etiologies of these cytopenias, some of which remain incompletely understood, create clinical conundrums and uncertainties about optimal management strategies. These cytopenias may cause additional sequelae, decreased quality of life, and increased resource use. Early cytopenias are typically attributed to lymphodepletion chemotherapy, however, infections and hyperinflammatory response such as immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome may occur. Early and prolonged cytopenias often correlate with severity of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Bone marrow biopsy in patients with prolonged or late cytopenias is important to evaluate for primary disease and secondary marrow neoplasm in both pediatric and adult patients. Commonly, cytopenias resolve over time and evidence for effective interventions is often anecdotal. Treatment strategies, which are limited and require tailoring based upon likely underlying etiology, include growth factors, thrombopoietin-receptor agonist, stem cell boost, transfusion support, and abrogation of infection risk. Here we provide our approach, including workup and management strategies, for cytopenias after CAR-T.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: T.J. has institutional research support from CTI Biopharma, SyneosHealth, Incyte; advisory board participation with Care Dx, Bristol Myers Squibb, Incyte, AbbVie, CTI, and Kite; education activity with Oncology APP, Binaytara Foundation, and ASH Highlights. T.S.O. has a consulting agreement with bluebird bio, Vertex, Medexus. F.L.L. has scientific advisory role/consulting fees from A2, Allogene, Amgen, bluebird bio, BMS/Celgene, Calibr, Caribou, Cellular Biomedicine Group, Cowen, Daiichi Sankyo, EcoR1, Emerging Therapy Solutions, GammaDelta Therapeutics, Gerson Lehrman Group, Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Takeda, Wugen, Umoja; contracts for service from Kite Pharma (institutional), Allogene (institutional), CERo Therapeutics (institutional), Novartis (institutional), bluebird bio (institutional), BMS (institutional), National Cancer Institute, Leukemia and Lymphoma Society; several patents held by the institution in their name (unlicensed) in the field of cellular immunotherapy; education or editorial activity in Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Considerations for etiologies and management of cytopenias after CAR T-cell infusion. ∗Remains speculative. #Antiviral prophylaxis is initiated early after CAR-T infusion and continued for 6 to 12 months. #Anti-PJP prophylaxis is started at day ∼28 until CD4+ cell count >200/mm3. #If the ANC has not recovered to >500/mm3 by day 7 to 10, consider institution of G-CSF. ANC, absolute neutrophil count; IEC-HS, hemophagocytic lymphohistiocytosis-like hyperinflammatory syndrome associated with immune effector cells; LD, lymphodepletion; LGL, large granular lymphocytosis; NGS, next generation sequencing; TA-TMA, transplant-associated thrombotic microangiopathy; TPO, thrombopoietin.
Figure 2.
Figure 2.
Patterns of neutrophil recovery in lymphoma patients treated with CAR T-cell therapy. Reproduced from Rejeski et al.
See this image and copyright information in PMC

Comment in

References

    1. Jain T, Bar M, Kansagra AJ, et al. Use of chimeric antigen receptor T cell therapy in clinical practice for relapsed/refractory aggressive B cell non-Hodgkin lymphoma: an expert panel opinion from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2019;25(12):2305–2321. - PubMed
    1. Kansagra AJ, Frey NV, Bar M, et al. Clinical utilization of chimeric antigen receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT) Bone Marrow Transplant. 2019;54(11):1868–1880. - PMC - PubMed
    1. Fried S, Avigdor A, Bielorai B, et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019;54(10):1643–1650. - PubMed
    1. Jain T, Knezevic A, Pennisi M, et al. Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies. Blood Adv. 2020;4(15):3776–3787. - PMC - PubMed
    1. Juluri KR, Wu QV, Voutsinas J, et al. Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. Blood Adv. 2022;6(7):2055–2068. - PMC - PubMed

Substances

LinkOut - more resources