Redefining hyperviscosity in acute leukemia: Potential implications for red cell transfusions in the microvasculature

Area of Science:

• Hematology
• Oncology
• Biophysics

Background:

• Hyperleukocytosis in acute leukemia can cause life-threatening leukostasis due to blood hyperviscosity.
• Hematocrit/hemoglobin levels significantly influence blood viscosity, but their role in leukemia-associated hyperviscosity is unclear.
• In vivo studies of microvascular obstruction are challenging, necessitating alternative models.

Purpose of the Study:

• To investigate the interaction between hematocrit/hemoglobin levels and acute leukemia in inducing in vitro leukostasis.
• To differentiate the mechanisms of leukostasis across various leukemia immunophenotypes.
• To establish thresholds for hematocrit/hemoglobin levels that exacerbate leukostasis.

Main Methods:

• Development of a multi-vessel microfluidic device simulating microvasculature.
• Analysis of patient samples and cell lines to assess leukostasis.
• Correlation of leukostasis with white blood cell count, hematocrit, and hemoglobin levels across different leukemia types.

Main Results:

• Leukostasis varied among leukemia immunophenotypes, influenced by white blood cell count and hematocrit/hemoglobin.
• Severe anemia was protective against in vitro leukostasis in lymphoid leukemias.
• Hematocrit/hemoglobin thresholds significantly increased leukostasis, particularly in B-cell acute lymphoblastic leukemia compared to T-cell acute lymphoblastic leukemia.
• Acute myeloid leukemia leukostasis was primarily driven by white blood cell count with minimal hematocrit/hemoglobin interaction.

Conclusions:

• Hematocrit/hemoglobin levels play a differential role in leukostasis depending on leukemia immunophenotype.
• Anemia may offer protection against leukostasis in certain acute leukemias.
• Findings suggest potential clinical strategies involving red blood cell transfusion management for acute leukemia patients.