Historical aspects and milestones in HCL 3
description of 26 patients with the disease by splenectomy. A 5-year overall survival rate of 61%
Bouroncle et al. in 1958 who provided a compre- was reported. However, toady splenectomy has
hensive description [1,13]. The change in the name basically been completely abandoned because of the
of the disease from leukemic reticuloendolethiosis to excellent results achieved with the purine analogues.
HCL is attributed to Schrek and Donnelly [14] who
observed and reported the hair-like projections under
Interferon
phase contrast microscopy in 1966. This finding
became an emblem for HCL and is almost pathog- In 1984, Quesada et al. [25,26] made a major
nomonic. However, subsequent studies revealed that contribution to the field with the remarkable ob-
a reniform nuclear contour and abundant cytoplasm servation that a interferon was effective in patients
are equally characteristic, and patients with other with HCL, and many groups reported similar results
lymphoproliferative disorders may show cells with with this agent thereafter [27–31]. Interferon was
similar cytoplasmic surface villous features. These seen then to induce responses, including some
initial descriptions of the disease established this rare complete remissions (CRs), particularly in previously
lymphoproliferative disorder as a distinct clinical untreated patients, and with modest toxicity. In one
entity with splenomegaly as generally the sole relatively large multicentre series, a 70% partial
predominant finding on physical examination. Pa- remission rate was observed [28]. Although inter-
tients typically present with various degrees of feron had great appeal, several limitations subse-
pancytopenia with circulating B-lymphocytes, usually quently became apparent. Maintenance therapy was
demonstrating the classic hair-like cytoplasmic pro- needed as most responding patients relapsed once
jections, although the latter may often be difficult to the drug was discontinued. Although toxicity from
discern in the peripheral blood because of their rarity interferon is reasonably mild, flu-like symptoms and
and the staining techniques. Lymphadenopathy, a fatigue are routinely observed. By the mid-1990s, the
common finding on physical examination in patients use of interferon had been largely replaced by purine
with many, if not most, lymphoproliferative disor- analogues. In the end, interferon followed the path of
ders, is uncommon in patients with HCL at splenectomy as just another treatment of historical
diagnosis, but are more frequently evident in patients interest only and is rarely, if ever, used today because
with relapsed and refractory disease [15]. A very rare of the development of the remarkably effective purine
HCL variant with features of both prolymphocytic analogues which are the treatments of choice for
leukemia and HCL has been described [16,17]. HCL.
Significant insight as to the origin of the malignant
cell was provided by several groups in the 1970s who
proved that the hairy cell is of B-cell origin [18–20] Purine analogues: a revolution in treatment
but although this is so, patients with HCL are treated
2-Chlorodeoxyadenosine
very differently from those with all other B-cell
lymphoproliferative disorders. An abrupt change in the treatment of patients with
HCL occurred immediately after the publication
by Piro et al. [32] from the Scripps Clinic in
Evolution of effective treatments 1990 showing that the deoxyadenosine analogue
2-chlorodeoxyadenosine (2-CdA) was remarkably
Splenectomy
effective in patients with HCL. In this initial report,
The first effective therapy, and in fact the mainstay of not only did 11 of 12 patients have CR evidenced by
therapy for 25 years after its initial description, was normalization of the peripheral blood and bone
splenectomy [3,21–24] often resulting in improve- marrow, but also remissions were durable with the
ment of the peripheral blood counts in the majority of longest being 3.8 years and none of the patients had
patients. Such responses are usually quite durable. relapsed at the time of publication. Remarkably,
The reason for the effectiveness of splenectomy still these results were achieved with a single 7-day
remains an enigma and it is possible that splenect- continuous infusion of the drug, an unprecedented
omy simply eliminates the site of sequestration of the achievement in view of the fact that effective
peripheral blood cells. However, Mintz and Golomb treatment of most malignancies requires repetitive
[22] reported that even patients with minimally cycles of therapy. Toxicity is quite modest and
enlarged spleen have a significant improvement in manifested primarily by myelosuppression and fever.
their peripheral blood counts after splenectomy. Since this initial report of only 12 patients, numerous
Later in 1986, Van Norman et al. [23] reported a other single institutions and cooperative groups
complete hematologic response in 67% and partial report similar outstanding results [33–35]. In all
hematologic response in 19% of 42 patients after series, 75–85% of patients achieved a CR after only
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