Consensus guidelines for classic Hairy Cell Leukemia: assessment of response and MRD

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 (HCLc) in the journal Blood.1

Key Highlights:
Assessment of Response
  • Involves inspection of hematologic parameters, complete physical examination (including spleen size), and bone marrow biopsy
  • In cladribine treated patients, it is advised follow-up bone marrow biopsy takes place 4–6 months after treatment completion
  • In pentostatin treated patients, bone marrow biopsy is normally performed after a clinical response (return to near normal levels of hematologic parameters); if evidence of response not observed by 6 months, then selection of a different treatment approach is recommended
Complete Response
  • Achieving a CR is associated with a longer disease-free period
  • Patients in CR should have returned to near normal levels of peripheral blood counts:2-3
    • Hemoglobin: >11g/dL (without transfusion)
    • Platelets: >10,000/µL
    • Absolute Neutrophil Count: >1,500/µL
  • Lymphocyte count (including subsets) may be low for a long period of time after treatment with a purine analog; bone marrow may need many months to recover and so hematologic parameters for CR are set at lower values than normal
  • On physical examination, regression of splenomegaly should have occurred
  • Whether CR has been achieved with or without MRD is determined by immunohistochemical stains of bone marrow trephine biopsy, such as CD20, DBA.44, and VE1
Partial Response
  • Defined as “near normalization of the peripheral blood counts with a minimum of 50% improvement in both organomegaly and bone marrow biopsy infiltration with HCL”1
  • Patients may be asymptomatic and not required further treatment for many years
Progressive Disease
  • Defined as “patients who have an increase in symptoms related to the disease or a 25% decline in their hematologic parameters”1
  • An increase in organomegaly by 25% also indicates disease progression
Determination of MRD after therapy
  • Defined as “HCL infiltrates recognizable by immunohistochemical stains, but not by conventional stains”4
  • It is common to estimate the percentage of cells in the bone marrow trephine biopsy using anti-CD20 antibodies or DBA.44
  • In patients treated with anti-CD20 mAb, use of anti-CD20 stains can be unreliable, so stains for other B-cell (CD79a) and/or HCLc (VE1) markers, or DBA.44, should be used
  • MRD predicted risk of relapse has been defined in groups:5
    • Group I – low risk of relapse: <1% positive cells
    • Group II – intermediate risk of relapse: 1–5% positive cells by IHC
    • Group III – higher risk of relapse: >5% positive cells by IHC

The authors state that, even though HCLc is not curable with currently available therapeutic options, patients can achieve durable remissions that do not require continues treatment unless symptoms return. The benefit of achieving a CR has been acknowledged, however total eradication of MRD potentially requires prolonged immunosuppressive treatment and so achieving a CR is not recommended as a well-established goal of treatment. Moreover, the authors advise that care is taken when identifying if a patient’s disease has progressed; a decline in blood counts can be due to the myelosuppressive effect of therapy and the patient will recover with observation. Lastly, the groups which define risk of relapsed predicted by MRD require validation in clinical studies.

  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. Cornet E. et al. Recommendations of the SFH (French Society of Haematology) for the diagnosis, treatment and follow-up of hairy cell leukaemia. Annals of Hematology. 2014 Dec; 93(12):1977–83. DOI: 10.1007/s00277-014-2140-y. Epub 2014 Jul 5.
  3. Jones G. et al. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant*. British Journal of Haematology. 2012 Jan; 156(2):186–95. DOI: 10.1111/j.1365-2141.2011.08931.x. Epub 2011 Nov 24.
  4. Noel P. Definition of remission, minimal residual disease, and relapse in hairy cell leukemia bone marrow biopsy histology and immunohistology specimens. Leukemia & Lymphoma. 2011 Jun; 52 Suppl 2:62–4. DOI: 10.3109/10428194.2011.565098. Epub 2011 Apr 4.
  5. Mhawech-Fauceglia P. et al. Potential predictive patterns of minimal residual disease detected by immunohistochemistry on bone marrow biopsy specimens during a long-term follow-up in patients treated with cladribine for hairy cell leukemia. Archives of Pathology & Laboratory Medicine. 2006 Mar; 130(3):374–7.

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.