B-cell hairy cell leukemia (B-HCL)

HAIRY CELL LEUKEMIA (HCL) / TRICHOLEUKEMIA / LEUKEMIC RETICULOENDOTHELIOSIS (95 % of all HCLs): a form of (indolent) chronic leukemia

Katayama variant
Cawley variant (type II HCL) : recovery with IFN-g therapy

Aetiology :

familial HCL is rarely encountered among the first degree relatives of HCL patients. A father and son, both of whom developed hairy cell leukemia, is presented in this report. The HLA haplotype shared by the father and son was A2, B18, BW6, CW7, DR3, DR10, and DQ8. Among these haplotypes, HLA A2 and Bw6 have previously been reported^ref

Symptoms & signs : enormous splenomegaly

. Lymphadenopathy is rare.
Laboratory examinations :

leukopenia with mild lymphocytosis . The white blood cell count rarely goes above 20 x 10⁹/L but neutropenia and monocytopenia are constant features (Catovsky D. Chronic lymphoid leukaemias. In: Hoffbrand AV, Lewis SK Tuddenham EG, eds. Postgraduate haematology, 4th ed. Oxford: Butterworth-Heinemann 1999:405–33)
cytomorphology : abundance of abnormal large mononuclear cells covered by hairlike villi (hairy cells) in the bone marrow, spleen, liver, and peripheral blood
cytogenetics : trisomy 12, 14q+
immunohistochemistry : tartrate-resistant AcP (TRAP)^ref
bone marrow biopsy : although circulating cells and clinical setting are similar to SMZL , in the bone marrow, hairy cells produce patchy infiltration with progressive replacement of normal hematopoietic series and low cellular density. Neoplastic infiltration is characteristically intermingled with extravasated red cells. The reticulin fiber content is almost invariably increased and accounts for the high frequency of "dry taps". In the spleen, HCL diffusely involves the red pulp, whereas the white pulp is atrophied. Cytochemically, hairy cells are diffusely and strongly positive for tartrate-resistant acid phosphatase (TRAP). The immunophenotype profile of HCL is similar to that of SMZL. However, HCL differs for CD25 and CD103 positivity. Ultrastructural analysis shows characteristic ribosome-lamella complex in hairy cell cytoplasm.
immunophenotype (CD5^-10 / CALLA^-11c^hi19⁺20⁺23^-25⁺27^-^ref103⁺, FMC7⁺, sIg⁺, cIg⁺)
V_H gene analysis reveals a homogeneous mutation status and suggests its marginal zone B-cell origin^ref

Differential diagnosis : SMZL

Therapy :

cladribrine / 2-chlorodeoxyadenosine (2-CdA) : 0.1 mg/kg/day IV continuous infusion days 1-7. Administer 1 cycle. Neutropenia grade 3 (16%) or 4 (71%) in first 135 consecutive patients treated, anemia grade 3 (20%) or 4 (2%), neutropenic fever (42%), documented infections (13%), thrombocytopenia (20%) => infectious mortality (1%), viral reactivation (3%). Emetogenic potential days 1-5 level 1^ref
IFN-a_2b : 2 MIU/m2 subcuteneously 3 times a week (escalation to 10 MIU/m² for nonresponders). Appropriate premedications. Grade 3 flu-like symptoms (19%), injection-site reaction (3%), CNS and PNS (2%), skin disorders (2%). Emetogenic potential level 1^ref
pentostatin / deoxycoformicin produces initial responses rates as high as 96%^ref
GR agonists are not effective

Codiagnosis :

HCL and polycythaemia rubra vera (PRV); however, in this patient, HCL occurred after the treatment of PRV with radioactive phosphorus^ref. Kampmeier et al described one case of PRV that followed the treatment of HCL with interferon; however, no cytogenetic abnormalities were found^ref
HCL and CML ^ref1,
ref2

Evolution : the incidence of second malignancies in HCL is reported as 8.7%^ref. Most of the second malignancies occurring in HCL are either solid tumours or other lymphoproliferative disorders, most commonly large cell lymphoma, but also multiple myeloma

and T cell leukaemia/lymphoma^ref. HCL => CML

^ref (cytogenetics confirmed the t(9;22) translocation. The patient ultimately developed ALL with additional chromosome abnormalities). There are reports that prolonged interferon treatment leads to an increased incidence of second malignancies in HCL. Kampmeier et al reviewed 69 patients with HCL who were given interferon and found that 6 patients developed haematological malignancies^ref. 3 patients had malignant lymphoma, one patient developed acute myeloid leukaemia

, and one developed PRV

. However neither our patient nor that of Reeves et al received IFN-a^ref. The study of Jacobs et al revealed 2 patients with HCL and haematological malignancies who had received chlorambucil^ref. A patient was treated with deoxycoformycin. Therefore, factors that lead to the development of second malignancies in HCL remain to be determined. It is possible that CML might have had its origin even before HCL was diagnosed in our patient; CML might have a prolonged silent or quiescent phase during which it can be cytogenetically detected despite an apparently normal blood count and film

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