Clinical Report: Anemia as a Standalone Condition in LGLL Patients

Overview

This report characterizes large granular lymphocytic leukemia (LGLL) presenting with isolated anemia, distinguishing it from cases with pure red cell aplasia (PRCA). It highlights diagnostic criteria, immunophenotypic features, and clinical outcomes in patients with isolated anemia without neutropenia or thrombocytopenia.

Background

Large granular lymphocytic leukemia (LGLL) is a clonal disorder marked by expansion of cytotoxic T or NK cells, often associated with neutropenia and thrombocytopenia. Diagnosis relies on identifying clonal LGL populations via morphology, immunophenotyping, and molecular studies. While anemia is common in LGLL, isolated anemia without accompanying cytopenias or PRCA is rare and understudied. This study retrospectively reviews LGLL patients presenting with isolated anemia to better define their clinicopathologic features and outcomes.

Data Highlights

Patients were selected from Mayo Clinic records (2005-2019) with T-LGLL or CLPD-NK diagnosis. Isolated anemia was defined as Hb <13 g/dL (males) or <12 g/dL (females) with normal neutrophil (≥1.5 × 10⁹/L) and platelet counts (≥150 × 10⁹/L). PRCA diagnosis required markedly decreased erythroid precursors, reticulocyte <0.5%, and no other causes. Flow cytometry, TCR gene rearrangement, STAT3 mutation analysis, and myeloid NGS were performed. Treatment response was assessed after ≥16 weeks, defining complete response as normalization of Hb and partial response as Hb improvement >1 g/dL or reduced transfusions by >50%.

Key Findings

• LGLL diagnosis requires at least 3 of 4 criteria including abnormal immunophenotype, clonality, intrasinusoidal infiltrates, and persistence >6 months.
• Isolated anemia in LGLL is defined by low Hb with normal neutrophil and platelet counts, distinguishing it from typical cytopenic presentations.
• PRCA is characterized by absent erythroid precursors and reticulocytopenia, differentiating it from isolated anemia cases.
• Immunophenotyping and molecular studies (TCR rearrangement, STAT3 mutations) support diagnosis and clonality assessment.
• Isolated anemia without PRCA in LGLL is rare and may be underrecognized due to lack of typical neutropenia or thrombocytopenia.
• Treatment response criteria include normalization or significant improvement in hemoglobin levels and transfusion requirements.

Clinical Implications

Clinicians should consider LGLL in patients presenting with unexplained isolated anemia even in the absence of neutropenia or thrombocytopenia. Comprehensive immunophenotypic and molecular workup is essential for accurate diagnosis. Recognizing isolated anemia presentations may prevent missed or delayed LGLL diagnoses and guide appropriate management.

Conclusion

Isolated anemia can be a standalone hematologic manifestation of LGLL distinct from PRCA-associated cases. Awareness and thorough diagnostic evaluation are critical for identifying this rare presentation and optimizing patient outcomes.

References

1. Swerdlow et al. 2017 -- WHO Classification of Hematolymphoid Neoplasms
2. Lamy and Loughran 2011 -- Clinical features and pathogenesis of LGLL
3. Loughran 2012 -- LGLL and associated autoimmune conditions
4. Koskela et al. 2007 -- STAT3 mutations in LGLL
5. Mayo Clinic Institutional Review Board 2005-2019 -- Retrospective LGLL patient data