Hairy cell leukemia: long-term follow-up
Table I. Age-adjusted incidence of hairy cell leukemia in Sweden 2000–2007 (n¼230) (incidence/million/year).
Age group 30–49 years
50–59 years 60–69 years 70–79 years 80–99 years
Males 3.3
11.6 9.7
16.2 20.4
Females 0.5
2.5 2.4 2.7 3.2
Both sexes 1.9
7.1 6.0 8.7 9.3
47
so-called ‘PICC lines’ (peripherally inserted central catheters), are used there is an increased risk for phlebitis. We do not see any reason for further use of intravenous administration, especially not through continuous iv infusions, and suggest that subcuta- neous or oral self-administration will be the standard of care in the immediate future. Bolus iv infusions could, however, be preferred for in-hospital treat- ment of acute myeloid leukemia.
characteristics of lymphoid leukemia cells the acti- vated nucleotides (mono-, di-, and triphosphorylated metabolites) accumulated rapidly and strongly in- tracellularly, with nucleotide concentrations being 2.5-log higher than plasma concentrations of the mother compound. Furthermore, the half-life (t1/2) of the active intracellular nucleotides was prolonged, with an initial t1/2 of 13 h, and a terminal t1/2 of 30 h [7]. Thus, the intracellular AUC was almost identical with continuous infusion as compared to 2 h inter- mittent infusions.We were also able to show that the bioavailability from subcutaneous injection was 100%, with a plasma profile resembling a 1 h intravenous infusion [8]. Finally, we could show excellent clinical response to subcutaneous cladri- bine in a large clinical study [9]. A brand for subcutaneous cladribine therapy of HCL has now for many years been registered in Europe and other parts of the world, as well as for some other indications, i.e. chronic lymphocytic leukemia and indolent lymphomas, in certain countries. This brand has a concentration of 2 mg/mL, which simplifies subcutaneous (sq) administration, com- monly up to 10 mg once daily. However, since there are no local side effects when cladribine is injected sq [9] it is quite feasible to give also the original 1 mg/ mL brand subcutaneously, although not formally approved, and there is no need for multiple injection sites. In our HCL study with subcutaneous cladri- bine [9] we used both concentrations depending on drug availability during the study period. We could also show that the bioavailability of
cladribine in the standard saline solution is about 50% when given orally. The loss is due to degrada- tion to chloroadenine, but since the interindividual variation was limited [8] we found that oral therapy was highly feasible in a large study of patients with previously untreated chronic lymphocytic leukemia [10]. Cladribine tablets, with an oral bioavailability of 40%, are now in 2010 approved for the treatment of multiple sclerosis [11] in some countries, and undergoing evaluation for registration in the USA and Europe. Continuous intravenous infusions are cumber- some, and when central venous catheters, including
Survival of patients with hairy cell leukemia in the new millenium
The Swedish Lymphoma registry, a part of the Swedish Blood Cancer Registry, includes 95% of all Swedish patients diagnosed with lymphoprolifera- tive disorders since the year 2000, and is likely to be the most reliable population-based registry world- wide. Need for treatment was reported in 84% of patients with HCL diagnosed up to 2007, and most were given cladribine. The overall 6-year survival is currently 80%. Among patients younger than 60 years at diagnosis (median age 52 years) the 6-year survival was 93%, whereas for patients more than 60 years (median age 72 years) the survival was 68%.
Long-term follow up of Scandinavian patients treated with cladribine in the early 1990s
Our treatment studies with cladribine starting in 1990 were the first to be conducted outside the Scripps Clinic. Thus they recruited symptomatic patients from all over Europe, but mainly from Scandinavia, at a time when this was the sole source of cladribine for clinical therapy [9,12]. Our popula- tion with HCL was therefore highly selected, similar to most US studies, with median ages at diagnosis and at cladribine treatment of 51.5 years and 54 years (mean ages 52 and 56 years), respectively. We have now been able to achieve long-term follow-up on
almost all Scandinavian patients (n¼85), and the 15- year survival from cladribine treatment is over 80% in patients below 60 years at inclusion, but less than 50% in those aged 60 years and over [Figure 1(A)]. Sixty percent of the younger patients were progres- sion-free at 15 years, as compared to one-third of the older [Figure 1(B)]. Most patients with progressive disease were retreated with cladribine. Overall survival from first cladribine treatment of previously untreated patients was better than for previously treated patients. There was a median of 3.3 years from diagnosis to inclusion of previously treated patients, whereas most untreated patients were given cladribine shortly following diagnosis [Figure 1C)]. Of interest was that previously treated patients had a median age of 3 yearsmore than that of the untreated
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