This study evaluates the application of the EHA/EBMT grading system for Immune Effector Cell-Associated Hematotoxicity (ICAHT) following CD19- and BCMA-directed CAR-T therapy in patients with relapsed/refractory B-cell malignancies. The grading system, which incorporates both the depth and duration of neutropenia, was applied to a cohort of 549 patients. The results showed that severe ICAHT was associated with increased rates of severe infections, nonrelapse mortality, and inferior survival outcomes. The ICAHT grading system demonstrated superior capacity to predict severe infections compared to the CTCAE grading system. The study highlights the clinical relevance of the novel grading system and supports its use in clinical trials evaluating CAR-T therapies. The ICAHT grading system is closely linked to multilineage cytopenias, transfusion dependence, and the need for supportive measures. Patients with severe or life-threatening ICAHT had higher rates of infections and adverse treatment outcomes. The study also found that the ICAHT grading system provides a more accurate assessment of hematotoxicity and its impact on patient outcomes. The findings suggest that the EHA/EBMT ICAHT grading system is a valuable tool for evaluating hematotoxicity after CAR-T therapy.This study evaluates the application of the EHA/EBMT grading system for Immune Effector Cell-Associated Hematotoxicity (ICAHT) following CD19- and BCMA-directed CAR-T therapy in patients with relapsed/refractory B-cell malignancies. The grading system, which incorporates both the depth and duration of neutropenia, was applied to a cohort of 549 patients. The results showed that severe ICAHT was associated with increased rates of severe infections, nonrelapse mortality, and inferior survival outcomes. The ICAHT grading system demonstrated superior capacity to predict severe infections compared to the CTCAE grading system. The study highlights the clinical relevance of the novel grading system and supports its use in clinical trials evaluating CAR-T therapies. The ICAHT grading system is closely linked to multilineage cytopenias, transfusion dependence, and the need for supportive measures. Patients with severe or life-threatening ICAHT had higher rates of infections and adverse treatment outcomes. The study also found that the ICAHT grading system provides a more accurate assessment of hematotoxicity and its impact on patient outcomes. The findings suggest that the EHA/EBMT ICAHT grading system is a valuable tool for evaluating hematotoxicity after CAR-T therapy.