Guideline sources The following summarized guidelines for the evaluation and management of hairy cell leukemia (HCL) are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2015) and the British Committee for Standards In Haematology (BCSH 2012). 1 2 Calculator Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Modified A Guidelines 1. Classification and risk stratification https://web.pathway.md/diseases/recBNg1qimnQEtpPf 1/5 6/24/23, 12:31 PM Hairy cell leukemia Pathway Prognosis: Recognize that the following biological factors are associated with poor outcomes: presence of TP53 mutations lack of somatic mutations in the IGVH genes (occur in a minor proportion of patients) VH4-34 family usage (more frequently seen in HCL variant). B Recognize that complete response is associated with a significantly longer disease-free survival than partial response. B 2. Diagnostic investigations Peripheral blood smear: As per ESMO 2015 guidelines, obtain peripheral blood smear and peripheral blood flow cytometry in patients with suspected classical HCL. B As per BCSH 2012 guidelines: Obtain peripheral blood smear for the diagnosis of HCL. B Obtain flow cytometric evaluation (for CD11c, CD25, CD103, and CD123) when liquid material is available. B 3. Diagnostic procedures Bone marrow biopsy: As per ESMO 2015 guidelines: Obtain flow cytometry in bone marrow aspirate and perform bone marrow trephine biopsy with immunohistochemistry in patients with suspected classical HCL. Perform bone marrow examination for the diagnosis, particularly after treatment, to assess response. B Obtain BRAF mutation analysis of exon 15 in difficult cases. B As per BCSH 2012 guidelines, perform bone marrow examination for the diagnosis of HCL. B Show 2 more 4. Medical management Indications for treatment, asymptomatic patients: As per ESMO 2015 guidelines, do not initiate treatment in asymptomatic patients. D Follow-up patients every 3-12 months with complete history, physical examination, CBC, and routine chemistry. D As per BCSH 2012 guidelines, avoid initiating immediate treatment at diagnosis in asymptomatic patients. Obtain active monitoring. D Indications for treatment, symptomatic patients: https://web.pathway.md/diseases/recBNg1qimnQEtpPf 2/5 6/24/23, 12:31 PM Hairy cell leukemia Pathway As per ESMO 2015 guidelines, initiate treatment in patients with symptomatic disease manifested by bulky or progressive, symptomatic splenomegaly cytopenias (Hgb < 10 g/dL and/or platelets < 100 10 /L and/or neutrophils < 1 10 /L), recurrent or severe infections, and/or systemic symptoms. B As per BCSH 2012 guidelines, initiate treatment in patients with symptomatic cytopenia or painful splenomegaly. B Purine analogs: As per ESMO 2015 guidelines: Offer purine analogs (cladribine or pentostatin) as initial treatment in young and fit patients with symptomatic HCL. B Consider administering cladribine at a dose of 0.12-0.15 mg/kg in a 2-hour infusion once weekly over 6 courses. B Administer a second course of cladribine, with or without rituximab, to achieve a complete response at least 6 months after the end of the first course in patients demonstrating a partial response after the first course of cladribine. C As per BCSH 2012 guidelines, offer purine analogs (cladribine or pentostatin) as first-line therapy in patients with HCL. B Interferon-alpha: consider offering interferon-alpha to increase the neutrophil count before nucleoside analog therapy in patients presenting with very severe neutropenia (neutrophil count < 0.2 10 /L). C Growth factors: As per ESMO 2015 guidelines, do not use adjunctive filgrastim routinely with cladribine in the treatment of patients with HCL and severe neutropenia. D As per BCSH 2012 guidelines, do not use growth factors routinely in the treatment of patients with HCL. D 5. Therapeutic procedures Blood product transfusion: administer only irradiated blood products in patients treated with cladribine or pentostatin and requiring transfusion, in order to minimize the risk of transfusion- associated GvHD. B Stem cell transplantation: consider performing allo-SCT in younger, heavily pretreated patients with HCL with multiple relapses and refractory to purine analogs and rituximab. C 6. Surgical interventions Indications for splenectomy: As per ESMO 2015 guidelines, consider performing splenectomy in patients with resistant massive symptomatic splenomegaly (> 10 cm below the costal margin) with accompanied low- level bone marrow infiltration. C https://web.pathway.md/diseases/recBNg1qimnQEtpPf 3/5 6/24/23, 12:31 PM Hairy cell leukemia Pathway Show 3 more As per BCSH 2012 guidelines, consider performing splenectomy in patients with symptomatic splenomegaly, particularly with minimal bone marrow involvement. C 7. Specific circumstances Pregnant patients: initiate treatment in pregnant patients with HCL only when truly warranted. B Show 3 more Patients with hairy cell leukemia variant: As per ESMO 2015 guidelines, offer cladribine (0.15 mg/kg on days 1-5) immediately followed by rituximab (375 mg/m every 8 weeks, beginning day 1) rather than cladribine or rituximab alone as the initial treatment in patients with HCL variant. B Show 4 more As per BCSH 2012 guidelines: Consider offering purine analogs with or without rituximab in selected patients. C Consider performing splenectomy to induce partial remission in selected patients. C 8. Preventative measures Antibiotic prophylaxis: As per ESMO 2015 guidelines, administer prophylactic co-trimoxazole (960 mg 3 times weekly) until the lymphocyte count increases to > 1 10 /L for the prevention of pneumocystis infections in patients with lymphopenia treated with nucleoside analogs. B As per BCSH 2012 guidelines, administer prophylactic co-trimoxazole until the lymphocyte count is 1 10 /L for the prevention of pneumocystis infections in patients treated with cladribine or pentostatin. B Antiviral prophylaxis: As per ESMO 2015 guidelines, administer prophylactic acyclovir (200 mg TID) until the lymphocyte count increases to > 1 10 /L for the prevention of herpes reactivation in patients with lymphopenia treated with nucleoside analogs. B As per BCSH 2012 guidelines, administer prophylactic acyclovir until the lymphocyte count is 1 10 /L for the prevention of herpes reactivation in patients treated with cladribine or pentostatin. B 9. Follow-up and surveillance Assessment of treatment response: As per ESMO 2015 guidelines, perform bone marrow examination for the assessment of response to treatment. B https://web.pathway.md/diseases/recBNg1qimnQEtpPf 4/5 6/24/23, 12:31 PM Hairy cell leukemia Pathway As per BCSH 2012 guidelines: Perform bone marrow examination once the blood count has recovered, typically 4-6 months after cladribine therapy or after 8-9 courses of pentostatin, for the assessment of response to purine analog therapy. B Assess for CD20 as the most useful immunohistochemical stain when assessing remission status post-treatment. B Management of relapsed/refractory disease: As per ESMO 2015 guidelines, offer retreatment with cladribine or pentostatin in patients with a relapse occurring after 12-18 months. B Show 5 more As per BCSH 2012 guidelines, treat residual disease with further purine analog therapy. B Show 2 more References 1. Gail Jones, Nilima Parry-Jones, Bridget Wilkins et al. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant. Br J Haematol. 2012 Jan;156 2 186 95. Open 2. T Robak, E Matutes, D Catovsky et al. Hairy cell leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v100 7. Open https://web.pathway.md/diseases/recBNg1qimnQEtpPf 5/5