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Regulation of Hematopoietic Stem Cells01:01

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations.

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Hematological toxicity is a common side effect of CAR T-cell therapy. This consensus provides a framework for grading and managing immune effector cell-associated hematotoxicity (ICAHT) to improve patient outcomes.

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Area of Science:

  • Hematology
  • Immunotherapy
  • Oncology

Background:

  • Hematological toxicity, including cytopenias, is the most frequent adverse event following chimeric antigen receptor (CAR) T-cell therapy, leading to significant infectious risks.
  • Existing practices for managing CAR T-cell therapy-related hematotoxicity show considerable heterogeneity worldwide.
  • There is a need for standardized guidelines to address the grading and management of immune effector cell-associated hematotoxicity (ICAHT).

Approach:

  • An international panel of 36 CAR T-cell experts from the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) convened to develop consensus recommendations.
  • Deliberations involved virtual conferences and a 2-day meeting to establish best practices for ICAHT.
  • Recommendations cover grading, risk factors, diagnostic workup, and management strategies for ICAHT.

Key Points:

  • A novel classification system for grading ICAHT is proposed, based on the depth and duration of neutropenia for early (day 0-30) and late (after day +30) phases.
  • Guidance is provided on identifying hemophagocytosis in severe hematotoxicity cases.
  • Consensus recommendations address management including growth factor support, anti-infective prophylaxis, transfusions, and stem cell interventions.

Conclusions:

  • Immune effector cell-associated hematotoxicity (ICAHT) is proposed as a distinct toxicity category following immune effector cell therapy.
  • A framework for grading ICAHT, including risk factor assessment and diagnostic workup, is established.
  • Expert recommendations offer a comprehensive approach to the short- and long-term management of ICAHT, aiming to standardize care and improve patient safety.