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1558 Part XI: Malignant Lymphoid Diseases Chapter 93: Hairy Cell Leukemia 1559

TABLE 93–2. Management of Hairy Cell Leukemia important. Considering both the risks and benefits of additional ther-
apy requires clinical judgment.
Determine accurate diagnosis There are several therapeutic options for treating patients with
• Marrow biopsy with immunohistochemical analysis either resistant disease or disease that had an early relapse following ini-
• Blood immunophenotypic characterization tial response. In general, if the patient achieved an initial response and
subsequently relapses within 1 to 2 years, an alternate agent might be
Decision on initiation of therapy selected for retreatment. Otherwise, retreatment with the initial ther-
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• Approximately 10 percent can be carefully followed on “watch apy can be considered if the first remission was durable. Most patients
and wait” approach but majority of patients require treatment will initially be treated with a purine nucleoside analogue. If there is an
• Determinants or symptoms prompting treatment: symptomatic early relapse, the alternate purine analogue may be selected for rein-
splenomegaly or laboratory studies showing: absolute duction. If patients initially received cladribine, pentostatin might be
neutrophil count <1000/μL; hemoglobin <10 g/dL; or platelet chosen for reinduction. In patients who demonstrate resistant disease,
count <100,000/μL
the identification of the BRAF V600E target has provided a therapeu-
Important assessments before therapy for leukemia tic strategy involving an inhibitor (e.g., vemurafenib) as investigational
• Presence or suspicion for infection therapy. Although patients have been reported to respond, this agent
• Adequate renal function is not yet FDA-approved for this indication. 24,25 Furthermore, immu-
• Previous exposure to hepatitis notoxin conjugates (e.g., HA22) have also been reported to produce
remissions in patients with resistant disease. The purine nucleoside
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Decision on frontline therapy analogues (cladribine and pentostatin) have also been effective in pro-
• Cladribine 0.1 mg/kg/day for 7 days continuous intravenous ducing long-term salvage remissions in patients with HCL in relapse. In
infusion 12,69,75 patients who have either resistant or relapsed disease, a combination of
• Cladribine 0.12 mg/kg/day for 5 days as 2-hour intravenous a purine analogue and a monoclonal antibody have also been used. 62,71
infusion vs. weekly infusion for 6 weeks 14
• Pentostatin 4 mg/m intravenous dose every 2 weeks until maxi-
2
mal response or failure 9,72,76 COURSE AND PROGNOSIS
Assessment of response The outlook for patients with HCL has markedly improved since its
68
• Following induction therapy, a marrow biopsy to document original description in 1958. Patients can now anticipate a near normal
quality of response and quantitate minimal residual disease life expectancy with the caveat that the disease will likely require close
(MRD) observation and retreatment for those who relapse. Survival at the end
• Methods for quantification of MRD with immunohistochemical of 1 year is estimated to be approximately 88 percent with 5-year sur-
21
stains and the optimal timing for MRD assessment are under vival at 77 percent in one longitudinal population-based report. Other
investigation long-term followup studies in the era of purine nucleoside therapy have
• In general, response assessment after cladribine is recom- identified similar results with 5-year survival being 90 percent and esti-
mended after 3 to 5 months. In contrast, response assessment mated 10-year survival at 81 percent. 72
following pentostatin is made at time of best clinical response Whereas overall survival has improved, there is an increased risk
Clinical investigations for resistant hairy cell leukemia of serious infection during the first year following diagnosis. The overall
• Alternate purine analogues alone or combined chemoimmuno- relative risk of a serious infection compared to a normal population is
therapy (e.g., bendamustine and rituximab) 77 2.59. This adjusted relative risk during the first year from diagnosis and
21
• Immunotoxin conjugates (e.g., moxetumomab pasudotox treatment is 8.04. The risk of serious infection is highest during the
first year, and then declines toward normal in subsequent years. This
[HA22] ) indicates that patients should be followed very closely during the initial
73
• BRAF V600E inhibitors (e.g., vemurafenib) 25,78 years following treatment. Full recovery of lymphocyte numbers and
Overall management strategies can be found in Refs. 62, 67, 71, and 79. function after therapy may require several years. Consequently, physi-
cians should follow their patients closely and document the recovery
of these immune effectors cells. Patients should receive vaccinations
treatment to eradicate MRD may involve continued therapy with its utilizing dead or attenuated viral vaccines, and avoid “live” viral vac-
attendant consequences of increased risk for infection or possibly a sec- cines while in remission. Prompt attention to early signs of infection is
ondary malignancy. Consequently, clinical judgment must be exercised important for health maintenance.
to achieve the optimal outcome for patients with this disease. An accu- The results of clinical investigations have markedly improved the
rate assessment of response to therapy may best be made several months outcome for this patient population. Clinical relapse will likely occur
74
following completion of initial induction therapy. In those who have because the current therapy controls the disease, but does not cure it.
71
achieved a complete response, careful followup is indicated. In those Despite the enormous progress made in managing these patients, con-
who had less than a complete remission, a determination will need to tinued clinical investigation is warranted in an effort to achieve the best
be made regarding salvage therapy versus close observation based upon outcome with durable complete remissions and minimal risk of infection.
blood count recovery.
REFERENCES
THERAPY AT RELAPSE 1. Bouroncle B, Wiseman AG, Doan CA: Leukemic reticuloendotheliosis. Blood 13:609–630,

The duration of response following initial therapy for HCL is variable. 1958.
The criteria for retreatment can be based upon recurrence of clini- 1A. Schrek R, Donnelly WJ: “Hairy” cells in blood in lymphoreticular neoplastic disease
and “flagellated” cells of normal lymph nodes. Blood 27:199–211, 1966.
cal symptoms and on the status of the blood count. A decision to 2. Quesada JR, Reuben J, Manning JT, et al: Alpha interferon for induction of remission in
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restart therapy before progressive severe pancytopenia has returned is hairy-cell leukemia. N Engl J Med 310:15–18, 1984.

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