Leukemia & Lymphoma, June 2011; 52(S2): 46–49
Hairy cell leukemia: epidemiology, pharmacokinetics of cladribine, and long-term follow-up of subcutaneous therapy
GUNNAR JULIUSSON & HENRIK SAMUELSSON; FOR THE SWEDISH LYMPHOMA REGISTRY
Stem Cell Center, Department of Laboratory Medicine, Lund University and Department of Hematology, Ska Hospital, Lund, Sweden
˚ne University
Abstract Hairy cell leukemia is often reported as a disease of young males. The male predominance is strong, 4:1, but the median age in the Swedish national compulsory cancer registry is similar to that of follicular lymphoma, i.e. 62 years. The overall 6-year survival in the Swedish registry of patients diagnosed since 2000 is 80%, 93% of patients560 years, and 68% of those460 years. The yearly risk of secondary cancers is 1.75%. Cladribine is a prodrug which is selectively activated intracellularly. The intracellular initial half-life is 13 h and the terminal half-life is 30 h. Subcutaneous injection once daily is simple and effective due to 100% bioavailability and no local side effects from injection, and self-administration is easy. Long-term follow-up of Scandinavian patients treated with cladribine (mostly as subcutaneous injections) in the early 1990s shows a480% 15-year survival from cladribine treatment in560 years of age, but550% in older patients. Survival from diagnosis of these patients was similar for those previously treated and untreated.
Keywords: Hairy cell leukemia, epidemiology, population-based, cladribine, subcutaneous, long-term survival
Epidemiology of hairy cell leukemia Hairy cell leukemia (HCL) is often said to be a disease of young males. Indeed the male predomi- nance is strong, 4:1 in all age groups. However, the age distribution is similar to that of follicular lymphoma, with a median age of 62 years (males 61 years, females 64 years). Forty-two percent of patients are over 65 years at diagnosis, and one- quarter over 75 years. The incidence of HCL in Sweden since 2000 according to age and sex is shown in Table I. Sweden has a national compulsory cancer registry, running since 1958, i.e. the year of the first HCL publication by Bouroncle et al. [1]. However, few patients were diagnosed with HCL in Sweden until the mid-1980s, when the successful therapies interferon [2] and deoxycoformycin [3] were re- ported. The incidence of HCL in Sweden has been stable since the late 1980s, and we thus believe that the reports in the new millennium are valid. Thus, HCL, like most other hematologic malignancies, is rare before 50 years of age, increases from age 50, and is most common in males over 70 years. However, older patients with HCL are rarely
Correspondence: Prof. Gunnar Juliusson, Ska E-mail:
Gunnar.Juliusson@med.lu.se
reported in the literature. This might reflect inade- quate diagnostic attempts with older patients, or reluctance to refer such patients to medical centers and clinical studies.
Pharmacology of cladribine: implications for treatment of hairy cell leukemia
Cladribine (2-chlorodeoxyadenosine; 2-CdA) was given as a 7-day continuous infusion in the early studies by Beutler [4]. This schedule was used since the plasma half-life is short, and with the insensitive techniques used in the 1980s the plasma concentra- tions were undetectable 24 h from the end of infusion, while in vitro studies suggested a need for continuous exposure for cytotoxicity. The serendipi- tous finding of an extraordinary efficacy in HCL [5] prompted adherence to the original treatment pro- tocol, although 2 h intravenous (iv) infusions were used for other indications. However, in 1990 we could show that the area under the curve (AUC) for plasma concentration of cladribine was similar for continuous intravenous and 2 h iv infusions [6], but more importantly we found that due to the metabolic
˚ne University Hospital and Lund University, Department of Hematology, Getingeva
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.565842
¨gen 4, Lund, 22185 Sweden.
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