Pocket Oncology (Pocket Notebook Series), 1st Ed.

HAIRY CELL AND PROLYMPHOCYTIC LEUKEMIA

Justin M. Watts and Martin S. Tallman

Hairy Cell Leukemia (HCL)

• ∼2% of all leukemias; 600–800 cases/y in US

• Median age of onset 52 y; more common in men (∼4:1) & Caucasians

Pathogenesis/Disease Biology

• HCL is an indolent B-cell lymphoproliferative disorder

• Expresses common mature B cell Ag (CD19, CD20, CD22, CD25, monotypic surface Ig) & does not express CD21 (an immature B cell marker)

• Characterized by aberrant expression of non-B cell markers (CD11c, CD103, CD123)

• Cytogenetic anomalies seen in ∼2/3 of pts (commonly chromosome 5)

• BRAF V600E Mt: Specific for classical HCL; present in ≥80% of cases

Clinical Presentation

• Constitutional sx, abdominal fullness/discomfort from massive splenomegaly, symptomatic or asx cytopenias (bleeding/easy bruising; recurrent infxn)

• Almost all pts (≥80%) have palpable splenomegaly; LAN usu not present

• Most pts p/w pancytopenia, w/c is often sev.; leukocytosis (from circulating hairy cells) in ∼10% cases

Diagnosis

• Peripheral blood smear: Small-medium-sized mononuclear cells w/eccentric nuclei, absent nucleoli, & finger-like cytoplasmic projections/indistinct borders (“hairy cells”)

• BM bx: Usu hypercellular w/infiltrating hairy cells; abundant cytoplasm surrounding nuclei may give “fried egg” appearance; often abundant mast cells; ↑ reticulin fibrosis common & may make marrow inaspirable/“dry tap”

• Immunophenotyping (flow cytometry): CD11c, CD19, CD20, CD22, CD25, CD103, CD123

• HCL variant: Morphologic features of both HCL & PLL (eg, cytoplasmic projections & prominent nucleoli); ↑ WBC; lacks CD25/CD123 expression; CD27(+); BRAF wild-type; tx plan often includes rituximab; can be resistant to purine analogs alone

Figure 26-1 Peripheral blood smear showing classical hairy cells

Treatment

• Indications for tx: Significant cytopenias (Hb < 11 g/dL, ANC < 1000/μL, Plt < 100000/μL); sx splenomegaly; constitutional sx (wt loss, NS)

• Purine analogs, esp cladribine (2-CdA), have revolutionized tx of HCL

• Cladribine: 1 cycle → hematologic CR rates approaching ≥90%; long remission durations (commonly y); excellent OS (≥95% at 5+ y); re-tx is effective for relapse (J Clin Oncol 2003;21:891)

• Cladribine given as continuous infusion (0.1 mg/kg/d) over 7 d; alternatives include once daily bolus dosing (0.14 mg/kg/d over 2 h) for 5 d

• Most common s/e is fever (40%), may require hospitalization or broad-spectrum oral abx for FN

• Unclear utility of post-tx BM bx → many pts have very long remission durations even if +MRD at 3–6 mos post-Rx

• MRD can be eradicated w/rituximab, but no evidence that this ↓ relapse rates or ↑ survival (Blood 2006;107:4658)

• Relapsed disease: Re-tx w/1 cycle of cladribine often effective w/duration of CR1 = CR2; pentostatin (requires multiple cycles); rituximab; clinical trial w/BRAF inhibitor or anti-CD22 drug conjugates (HA22, BL22) (J Clin Oncol2012;30:1822)

• Given indolent nature of disease & effectiveness of cladribine, many pts may have nl or near-nl life spans

Prolymphocytic Leukemia (PLL) → Exists in B & T cell varieties; both are rare, aggressive malignancies

B Cell Prolymphocytic Leukemia (B-PLL)

• Clonal disorder of mature, ABC (“prolymphocytes”); p53 deletions/Mt implicated in >50% cases

• Very rare, <1% of B cell leukemias, usu affects older adults

• Pts typically p/w leukocytosis (commonly >100000/μL) & anemia, may have other cytopenias, ++splenomegaly, B sxs (malaise, fever, NS), infrequently LAD

Diagnosis (B-PLL)

• B-prolymphocytes must comprise ≥55% of lymphocytes in the PB

• Peripheral blood smear: Numerous “prolymphocytes” → medium-sized cells w/moderately condensed chromatin & a prominent nucleolus

• BM aspirate & bx w/flow cytometry, cytogenetics, molecular studies to confirm dx

• DDx includes more common B cell malignancies such as CLL & leukemic phase of MCL

• Distinguish from variant HCL & T-PLL (w/c can have similar morphologic appearance & clinical presentation) by immunophenotyping and/or clonal rearrangement of Ig genes

• Immunophenotype: Bright expression of surface Ig w/light chain restriction, bright CD20; (+)CD19, CD22, CD79a, & FMC7; weak or absent CD5, CD23

• Cytogenetics: Important to r/o mantle cell lymphoma → t(11;14)

Prognosis/Treatment (Mayo Clin Proc 2005;80:1660)

• Clinical course can be variable, but often resistant to CT & median OS 3 y

• High WBC & anemia appear to predict poor response/survival

• No standard tx, but usu treated w/a CLL-like regimen such as FCR (fludarabine, cyclophosphamide, rituximab) or alemtuzumab

• Consider splenectomy/splenic irradiation for refractory, sx splenomegaly

• In younger pts w/good PS, strongly consider allogeneic HCT if suitable donor

T Cell Prolymphocytic Leukemia (T-PLL)

• Clonal disorder of post-thymic, mature T cells (“prolymphocytes”); abnl chromosome 14/TCL1 gene implicated in most cases

• Rare, ∼2% of mature lymphocytic leukemias, usu affects older adults

• ↑↑ incidence in pts w/ataxia telangiectasia, age of onset 20–30 y

• Clinical presentation similar to B-PLL w/leukocytosis (often >100000/μL), cytopenias, & splenomegaly, but hepatomegaly & LAD more common in T-PLL, can also see skin involvement & serositis

Diagnosis

• Morphology: Monomorphic, medium-sized lymphocytes, prominent nucleolus, cytoplasmic protrusions; small cell variant (20%); rare Sezary cell-like variant (cerebriform nuclei)

• Immunophenotyping → bright expression of CD52, pan-T cell markers (CD2, CD3, CD7)

• Clonal TCR gene rearrangement

• Distinguish from MF, T cell LGL leukemia, & adult T cell leukemia/lymphoma (w/c is a/w the HTLV-1 virus)

Prognosis/Treatment (Blood 2012;120:538)

• Worse prognosis than B-PLL, median OS < 1 y

• Alemtuzumab (anti-CD52 Ab, Campath) is the tx of choice → good RR (∼60% CR; most other pts have PR) but relapse almost always occurs

• Alemtuzumab depletes T cell niche & very immunosuppressive (high risk of CMV infxn, etc.)

• Must consolidate w/allogeneic HCT in appropriate candidates for chance of cure

• Typically not responsive to CT, pentostatin has some activity (<50% ORR)