Table 4.

Diagnostic workup

Diagnostic categoryIncluded diagnostic testsWhen to initiateAdditional comments
Basis workup (tier 1) • Check medication list for myelotoxic co-medications
• Rule out active infections: blood cultures, procalcitonin
• Vitamin deficiency: B12, folic acid
• Consider secondary HLH/MAS: serum ferritin 
In case of severe neutropenia (ANC <500/µL) beyond day +7 after CAR-T infusion Low threshold to perform (minimal workup) 
Advanced workup in case of severe ICAHT (tier 2) • Bone marrow aspiration and biopsy
• Advanced viral studies (parvovirus B19, CMV) 
Grade 3 or higher ICAHT beyond day +14 Especially in patients with underlying marrow infiltration 
Clinical suspicion for therapy-related myeloid neoplasm Immunohistochemistry, flow cytometry, cytogenetics; next-generation sequencing (myeloid panel) In case of persistent bone marrow aplasia beyond 1 month; unclear and/or new-onset cytopenia; cytopenia refractory to therapeutic measures t-MN after CAR-T therapy is an emerging field of study* 
Diagnostic categoryIncluded diagnostic testsWhen to initiateAdditional comments
Basis workup (tier 1) • Check medication list for myelotoxic co-medications
• Rule out active infections: blood cultures, procalcitonin
• Vitamin deficiency: B12, folic acid
• Consider secondary HLH/MAS: serum ferritin 
In case of severe neutropenia (ANC <500/µL) beyond day +7 after CAR-T infusion Low threshold to perform (minimal workup) 
Advanced workup in case of severe ICAHT (tier 2) • Bone marrow aspiration and biopsy
• Advanced viral studies (parvovirus B19, CMV) 
Grade 3 or higher ICAHT beyond day +14 Especially in patients with underlying marrow infiltration 
Clinical suspicion for therapy-related myeloid neoplasm Immunohistochemistry, flow cytometry, cytogenetics; next-generation sequencing (myeloid panel) In case of persistent bone marrow aplasia beyond 1 month; unclear and/or new-onset cytopenia; cytopenia refractory to therapeutic measures t-MN after CAR-T therapy is an emerging field of study* 

ANC, absolute neutrophil count; CMV, cytomegaly virus; HLH/MAS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome; ICAHT, immune effector cell-associated hematotoxicity; t-MN, therapy-related myeloid neoplasm.

*

Incidence rate as high as 6% of t-MN after CAR T-cell infusion (see Gurney et al., EHA 2023; abstract number S26387 ).

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