Leukemia & Lymphoma, October 2009; 50(S1): 23–26
Long-term follow-up studies in hairy cell leukemia
MICHAEL R. GREVER
1
& PIER LUIGI ZINZANI
2
1
Department of Medicine, The Ohio State University, Columbus, OH, USA and
2
Institute of Hematology and Medical
Oncology, University of Bologna, Bologna, Italy
Abstract
Enormous progress has been made in the management of patients with hairy cell leukemia (HCL) over the past 50 years since
this disease was initially described in 1958. The introduction of the two commonly used purine nucleoside analogs
(pentostatin and cladribine, respectively) has independently changed the natural history of this rare malignancy. Both agents
are equivalent in terms of response and long-term results. Advances in therapy are being further pursued with inclusion of
monoclonal antibodies (e.g. rituximab) and other immunotherapeutic approaches. Patients with this disease now can live a
near normal life expectancy, but the disease has not yet been cured. Clinical trials must continue to address the remaining
unanswered questions.
Keywords: Hairy cell leukemia, long-term, follow-up
In1958,Bouroncleetal.describedtheclinicalentityof long-term results of the initial studies. One of the
leukemicreticuloendotheliosiswhichisnowknownas largest randomized trials of initial therapy for patients
hairycell leukemia (HCL) [1].This disease presents a with this disease involved the treatment with either
truly remarkablestoryrevealing thebenefits ofclinical thrice weekly a-interferon or pentostatin delivered
research. Patients with HCL were confronted with a intravenously every 2 weeks [3]. Patients were treated
slowprogressivelymphoidmalignancycomplicatedby for 6–12 months depending upon their response. If a
bone marrow failure and serious infections. Thera- complete remission was achieved on the pentostatin
peutic intervention was limited to either careful arm, two additional doses of the drug were delivered
titration of alkylating agents or splenectomy, but the before stopping therapy. On the interferon arm, the
inability to alter the clinical course of the patients with agent was delivered for up to 12 months or until the
thisrareformofleukemiadidnotsubstantiallychange patientachievedacompleteresponse.Ifpatientsfailed
until the introduction of a interferon in 1984 [2]. toachieveanobjectiveresponseat6months,theywere
Shortly thereafter, observations that a purine nucleo- crossed over to the alternative therapy. Patients were
sideanalog(pentostatin)couldinduceahighdegreeof then observed for the duration of response and the
complete remissions in this previously ‘untreatable’ frequency of complications (including infections). In
chronic leukemia changed the natural history of this 1995,Greverreportedthatthecompleteresponserate
disease in record time [3–8]. Another purine nucleo- toinitialpentostatininthismulti-institutionaltrialwas
side analog (cladribine) produced identical high 76%,andthecompleteresponseratewasonly11%on
remission rates with a single course of therapy [9]. a-interferon. In patients who crossed over from initial
The follow-up studies with both of these analogs interferon to pentostatin, the complete response rate
showed that remissions were long-lived for the most was 66% (Table I).
part, yet*30–40% of patients will relapse with long- In 2000, Flinn et al. reported the long-term results
term follow-up [10–13,14–16]. for 241 patients on this same trial who were evaluable
Approximately 25 years following the introduction for the follow-up. The median duration of the follow-
of purine nucleoside analog therapy, we now have the up was 9.3 years. The projected 10-year overall
Correspondence: Michael R. Grever, Department of Medicine, The Ohio State University, Columbus, Ohio, USA. E-mail: michael.grever@osumc.edu
ISSN 1042-8194 print/ISSN 1029-2403 online C211 2009 Informa Healthcare USA, Inc.
DOI: 10.3109/10428190903141820
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46