The study evaluates the novel EHA/EBMT grading system for Immune Effector Cell-Associated HematoToxicity (ICAHT) in a large cohort of patients treated with BCMA- or CD19-directed CAR-T therapy for refractory B-cell malignancies. The ICAHT grading system, which incorporates both the depth and duration of neutropenia, was applied to 549 patients, and its clinical implications were assessed. Key findings include: 1. **Correlation with Severe ICAHT**: Severe ICAHT was strongly associated with the cumulative duration of severe neutropenia, the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. 2. **Disease-Specific Differences**: Severe ICAHT was more frequent in patients with mantle cell lymphoma (MCL) compared to those with large B-cell lymphoma (LBCL) and multiple myeloma (MM). 3. **Infectious Complications**: Patients with severe ICAHT had a significantly higher rate of severe infections (49% vs 13%), increased nonrelapse mortality (NRM) (14% vs 4%), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%). 4. **Superior Discrimination**: The ICAHT grading system demonstrated superior discrimination for severe infections compared to the Common Terminology Criteria for Adverse Events (CTCAE) grading (c-index 0.73 vs 0.55, P < .0001). The study highlights the clinical relevance of the EHA/EBMT ICAHT grading system and supports its use in reporting ICAHT severity in clinical trials evaluating CAR-T therapies.The study evaluates the novel EHA/EBMT grading system for Immune Effector Cell-Associated HematoToxicity (ICAHT) in a large cohort of patients treated with BCMA- or CD19-directed CAR-T therapy for refractory B-cell malignancies. The ICAHT grading system, which incorporates both the depth and duration of neutropenia, was applied to 549 patients, and its clinical implications were assessed. Key findings include: 1. **Correlation with Severe ICAHT**: Severe ICAHT was strongly associated with the cumulative duration of severe neutropenia, the presence of multilineage cytopenias, and the use of platelet and red blood cell transfusions. 2. **Disease-Specific Differences**: Severe ICAHT was more frequent in patients with mantle cell lymphoma (MCL) compared to those with large B-cell lymphoma (LBCL) and multiple myeloma (MM). 3. **Infectious Complications**: Patients with severe ICAHT had a significantly higher rate of severe infections (49% vs 13%), increased nonrelapse mortality (NRM) (14% vs 4%), and inferior survival outcomes (1-year progression-free survival: 35% vs 51%, 1-year overall survival: 52% vs 73%). 4. **Superior Discrimination**: The ICAHT grading system demonstrated superior discrimination for severe infections compared to the Common Terminology Criteria for Adverse Events (CTCAE) grading (c-index 0.73 vs 0.55, P < .0001). The study highlights the clinical relevance of the EHA/EBMT ICAHT grading system and supports its use in reporting ICAHT severity in clinical trials evaluating CAR-T therapies.