CLL/SLL

Consensus guidelines for classic Hairy Cell Leukemia: classification and diagnosis

On 2nd February 2017, Michael R. Grever from the Ohio State University James Cancer Hospital, Columbus, OH, USA, and colleagues published consensus guidelines for the diagnosis and management of classic Hairy Cell Leukemia patients in the journal Blood.1

Key Highlights:

 

Classification:
  • Hairy Cell Leukemia (HCL) is a rare variant of CLL
  • In 2008, the WHO established that the classic (HCLc) and even rarer variant (HCLv) forms of the disease are separate entities2
Symptoms:
  • Fatigue and infections are common symptoms of HCLc
  • Previously, the majority of patients (around 90%) had enlargement of the spleen; however, this seems less common now due to earlier disease detection
  • Frequently, patients are identified due to incidental findings of pancytopenia
Diagnosis:
  • First assessment should include examination of peripheral blood smear with differential count:
    • Monocytopenia is characteristic of HCLc; rare in HCLv
    • Leukemic cells are rare in most cases; hairy cells are medium sized containing a reasonable amount of pale blue cytoplasm, reniform shaped nuclei, open chromatin, absent nucleoli, and characteristic “hairy” projections of the cytoplasmic border
    • HCLc cells: CD19­+, CD20+, CD11c+, CD25+, CD103+, CD123+ co-expression; intensely stain for CD200; negative for CD27
    • Mostly, HCLv patients are negative for CD123 and CD25
  • Trephine Bone Marrow (BM) biopsy & aspirate are essential to determine the extent of infiltration:
    • A cellular aspirate is often difficult to attain due to a dry tap caused by extensive fibrosis
    • Around 10% patients have hypocellular BM biopsy
    • Immunohistochemical stains for CD20 and annexin-1, and VE1 stain for BRAFV600E, should be performed
  • BRAFV600E
    • BRAFV600E mutation, found in most HCLc patients, is not present in HCLv patients
    • Recommended all HCL patients are assessed for the mutation using a sensitive molecular assay that can detect the <10% leukemic cells in peripheral blood/BM aspirate diluted with blood (due to dry tap)3
    • Highly sensitive techniques (e.g. allele-specific PCR or NGS) should be used rather than less sensitive techniques (e.g. Sanger sequencing, pyrosequencing, or melting curve analysis) to avoid false-negative results
    • If highly sensitive technique is not readily available, VE1 stain of BM may detect BRAFV600E

The authors stated that huge progress in HCLc management of has contributed to improved outcomes in many patients. The creation of consensus guidelines builds a framework to continue improving the care, survival, and quality of life for patients with this rare hematologic malignancy. It was concluded that patients should still follow current recommendations for cancer screening and careful follow-up with a dermatologist.

References:
  1. Grever M.R. et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood. 2017 Feb 2; 129(5):553–560. DOI: 10.1182/blood-2016-01-689422. Epub 2016 Nov 30.
  2. Piris M.A. et al. Splenic B-cell lymphoma/leukemia, unclassifiable. In: Swerdlow S.H. et al. WHO classification of tumours of haematopoietic and lymphoid tissues, 4th Lyon, France: IARC. 2008: 191–193.
  3. Tiacci E. et al. Targeting mutant BRAF in relapsed or refractory Hairy Cell Leukemia. New England Journal of Medicine. 2015; 373(18):1733–1747.

 

Abstract:

Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.