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Consensus guidelines for classic Hairy Cell Leukemia: treatment at relapse, and infection prevention and treatment

Feb 21, 2017

On 2 ndFebruary 2017, Michael R. Greverfrom the Ohio State University James Cancer Hospital, Columbus, OH, USA, and colleagues publishedconsensus guidelines for the diagnosis and management of classic Hairy Cell Leukemia patients (HCLc) in the journal Blood. 1

Key Highlights:

Treatment at relapse

  • Many patients require re-treatment for disease relapse
  • Overall, it has been noted that first remission is often more durable than following remissions and is associated with a better chance of achieving CR
  • When deciding re-treatment strategy, a review of the patient’s treatment history should be performed while considering high-risk grouping
  • If patient demonstrates poor-risk features, identifying underlying reasons for the poor initial response may aid the decision on whether to pursue investigational therapies
  • Criteria for re-treatment at relapse include return of symptomatic disease (such as splenomegaly), or decrease of hematologic parameters such as progressive anemia, thrombocytopenia, or neutropenia
  • If previous remission was:
    • >60 months: consider re-treatment with initial therapy
    • >24 months: consider re-treatment with purine analog combined with anti-CD20 mAb, or clinical trial
    • <24 months: consider alternative treatment (including investigational therapies) once accuracy of diagnosis confirmed
  • In selected patients, older treatment approaches (interferon alpha, splenectomy, rituximab) or enrollment in clinical trials represent important options
  • When to re-treat is an important decision: managing the reappearance of hairy cells in the peripheral blood/bone marrow must be weighed against the toxicity of immunosuppressive treatment

Investigational approaches

  • The BRAF inhibitor vemurafenib has resulted in CRs in R/R patients, however relapse after vemurafenib treatment has been found to be common
  • Encouraging results with newer BRAF inhibitors (such as dabrafenib) have been reported
  • AEs with BRAF inhibitors include: skin rash, arthralgias, arthritis, and secondary skin tumors
  • Ibrutinib is being investigated for HCLc patients who did not achieve optimal response to standard therapies in a NCI multi-center trial ( NCT01841723)
  • HA-22 (or moxetumomab pasudotox), an immunotoxin conjugate developed at the National Institutes of Health, is being investigated in multi-center clinical trials 2

Prevention and treatment of infection

  • Infection is the most common cause of death in HCLc patients
  • Patients often have pre-existing neutropenia and/or monocytopenia, so bacterial, viral, and opportunistic infections should be expected
  • Treatment for HCLc is often immunosuppressive, and so places patients at further risk of infection
  • Myeloid growth factors can be considered in patients with active infection, on a case-by-case basis
  • Live viral vaccines should be avoided; patients can receive killed viral vaccines
  • Patients who have received prior therapy with purine analogs should receive irradiated blood products if they require a transfusion, due to persistent lymphopenia as a result of the treatment
  • Hepatitis history should be documented to avoid liver toxicity as a result of immunosuppressive anti-leukemia therapy causing viral reactivation
  • Screening for previous hepatitis exposure before HCLc therapy is recommended

The authors state that patients need to be educated about how to prevent infection and the symptoms to be aware of which may require medical attention (such as fever during neutropenia, or rash indicative of varicella zoster infection). Currently, no specific prevention strategies have been defined in clinical trials and practices vary between institutions, therefore evaluation of prevention and infection treatment strategies is an area of much needed research. Moreover, there is no data indicating that patients respond to vaccines; further investigation into the effectiveness of vaccination prevention strategies is required.


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.

  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. Kreitman R.J. et al.Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. Journal of Clinical Oncology. 2012 May 20; 30(15):1822–8. DOI: 10.1200/JCO.2011.38.1756. Epub 2012 Feb 21.