Development of ALL-Hematotox: Predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia Journal Article
| Authors: | Nair, M. S.; Silbert, S. K.; Rejeski, K.; Wilson, K. A.; Lamble, A. J.; Valtis, Y.; Yates, B.; Morales Arana, A.; Shouval, R.; Curran, K.; Gardner, R. A.; Shalabi, H.; Annesley, C.; Park, J. H.; Subklewe, M.; Shah, N. N. |
| Article Title: | Development of ALL-Hematotox: Predicting post-CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia |
| Abstract: | Immune effector cell–associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. Although ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (≥14 days of absolute neutrophil count [ANC] <500/μL), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC <500/μL) was 13 days (95% confidence interval, 10-16 days), with 83 (53%) experiencing grade ≥3 ICAHT. Applying CAR-HT, nearly 90% were classified as high risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and postinfusion neutropenia (r = 0.64, P < .0001), we developed the ALL-Hematotox (ALL-HT) score, which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve = 0.84, P < .0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days; P < .0001), fewer rates of complete response (88% vs 98%; P = .03), and shorter median overall survival (9.8 vs 24 months; log-rank P = .0002). ALL-HT was also validated in 2 independent cohorts. The ALL-HT score refines a widely accepted predictive model of postinfusion hematotoxicity, which is applicable in B-ALL. © 2025 American Society of Hematology |
| Keywords: | adolescent; adult; child; controlled study; major clinical study; fludarabine; neutropenia; neurotoxicity; c reactive protein; disease association; mantle cell lymphoma; multiple myeloma; thrombocyte; blood toxicity; cohort analysis; cyclophosphamide; hemoglobin; high risk patient; disease severity; chimeric antigen receptor; lactate dehydrogenase; cytopenia; cd19 antigen; ferritin; platelet count; diffuse large b cell lymphoma; disease burden; human; male; female; article; b cell acute lymphoblastic leukemia; absolute neutrophil count; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; cell therapy agent; brexucabtagene autoleucel |
| Journal Title: | Blood |
| Volume: | 145 |
| Issue: | 11 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2025-03-13 |
| Start Page: | 1136 |
| End Page: | 1148 |
| Language: | English |
| DOI: | 10.1182/blood.2024025910 |
| PUBMED: | 39561284 |
| PROVIDER: | scopus |
| PMCID: | PMC11923441 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work