Smudge Cells in Chronic Lymphocytic Leukemia: Pathophysiology, Laboratory Considerations, and Clinical Significance.

Chronic lymphocytic leukemia (CLL) is the most commonly encountered leukemia in the clinical laboratory. Cytoskeletal defects in CLL lymphocytes can result in the formation of up to 75% smudge cells (SCs) during blood film preparation. Failure to account for these damaged lymphocytes in the white blood cell (WBC) differential diminishes the accuracy and reproducibility of the results. Lacking clear practice standards on handling SCs in CLL, different laboratories may employ different methods to mitigate SC-induced errors. This review explores the pathophysiology of SCs, their effect on WBC differentials in CLL, and how these results can impact clinical decisions. The pros and cons of various SC corrective methods are described to assist laboratories in developing an optimized protocol to reduce errors and inconsistencies in WBC differentials. Finally, the potential utility of SC enumeration as an indicator of CLL prognosis is discussed in terms of laboratories with differing access to technology.

Method comparison study of peripheral blood CD34+ count performed on an Abbott CELL-DYN Sapphire hematology analyzer versus flow cytometry reference procedure (modified ISHAGE).

INTRODUCTION: CD34+ cell enumeration is a critical parameter used to determine the timing of apheresis collections of hematopoietic progenitor cell products (HPC(A)). Automated hematology analyzers equipped with flow cytometry capabilities may be a solution to the problem of limited access to standard flow cytometry testing. METHODS: We compared CD34+ cell enumeration using a reference flow cytometry procedure employing modified International Society of Hematotherapy and Graft Engineering (ISHAGE) analysis with a hematology analyzer /flow cytometer hybrid (CELL DYN (CD)Sapphire) using a sequential gating analysis designed to emulate the ISHAGE gating strategy. RESULTS: CD34+ cell values obtained from the ISHAGE and CD Sapphire analysis were plotted and compared in a linear regression analysis which showed a high degree of correlation (R2=0.96). No statistically significant (p=0.53) differences in CD34+ cell enumeration values were observed between the flow cytometer and automated hematology analyzer using manual analysis schema. CONCLUSIONS: We have demonstrated that an automated hematology analyzer equipped with a flow module can provide CD34+ cell enumeration results in the peripheral blood for clinical decision algorithms without the need for a dedicated flow cytometry laboratory.

Comparison of manual hematocrit determinations versus automated methods for hematopoietic progenitor cell apheresis products.

BACKGROUND: Allogeneic hematopoietic stem cell donor selection is based primarily on human leukocyte antigen degree of match and it often occurs without regard to the red blood cell (RBC) compatibility between donor and recipient. When major ABO-mismatched grafts are infused, it is imperative that an accurate determination of the incompatible RBC content is made to ensure that the product is safe for infusion. RBC content determination requires the hematocrit (Hct) parameter which can be obtained via manual (directly measured) or automated (calculated) methods. STUDY DESIGN AND METHODS: Ninety-seven apheresis hematopoietic progenitor grafts were assessed for Hct by manual testing and by four commercially available automated hematology analyzer instruments. A clinical model was developed to assess the frequency of unnecessary RBC reductions or alteration in standard infusion practice. RESULTS: Significant (p < 0.001) differences were observed where the manual Hct value was markedly lower than automated Hct values. At stringent incompatible RBC threshold of 10 mL, the number of preventable RBC reduction procedures ranged from 18% to 69%. CONCLUSION: Accurate determination of RBC content of hematopoietic progenitor grafts is essential for patient safety. Despite the rapidity and convenience offered by automated Hct methods, they significantly overestimate the incompatible RBC content of grafts, which may trigger unnecessary RBC reduction procedures or split infusions. In products where automated Hct methods indicate excessive amounts of incompatible RBCs are present, we advise the performance of confirmatory testing with a manual Hct method to ensure that the automated Hct value is not a false positive.