Pentostatin and cladribine for hairy cell leukemia
majority of these achieved a durable CR. Patients whose response does not improve could perhaps benefit from the addition of rituximab. We have not encountered problems with delivery of this second cycle in terms of cytopenias or infectious complica- tions. However, in rare patients with prolonged cytopenias, provided this is due to BM aplasia and not to residual HCL, it would be advisable to delay any further treatment until count recovery. No variable was found to be a significant predictor
of response to treatment in our series. In multivariate analysis the most significant predictor of shorterDFS was response (PR vs. CR), followed by low hemo- globin and/or platelet counts. The median DFS for patients with low hemoglobin (510 g/dL) and/or low
platelets (51006109/L) was 9 years versus 20þ years (not reached) for all others [7]. Older age only showed a significant association with shorter DFS when response was not included in the model. Other available variables were gender, disease burden (white blood count and spleen size), time from diagnosis to treatment, type of treatment (pentostatin vs. cladribine), and other prior therapy. None of these was a predictor of DFS.
In the 21st century patients with hairy cell leukemia can anticipate normal life-expectancy
The number of deaths in our series of patients was 45 (19%), which is equivalent to the rate for the general population when matched by age and sex. Overall survival 15 years after first treatment was 78%, or 96% when non-HCL-related deaths were censored. Only eight deaths (3.4%) were HCL-related, follow- ing refractory disease, of which all but one occurred before 1998 [7]. In the context of this normal life-expectancy, other
concerns regarding the late effects of treatment become important to patients. Excluding non-mela- noma skin cancers, 31 patients in our series devel- oped second malignancies (28 subsequent to HCL treatment). This number was equivalent to the incidence of cancers in the general population, matched by age and sex [7]. We have no documented cases of aplastic anemia or myelodysplastic syn- drome. In addition, both male and female patients treated
with purine analogs in our series have proceeded to parenthood, with normal unassisted pregnancies and delivery of healthy children.
Conclusion
Although still not regarded as a curable disease by conventional criteria, the majority of patients with HCL can now expect a normal lifespan, without
23
significant impairment of their quality of life through treatment-related effects. Even the minor- ity of patients who have multiply relapsed or refractory disease can be helped by more novel treatment interventions with monoclonal antibodies [8]. Given the excellent survival, the emphasis has turned to ensuring the safest and least intrusive means of delivering effective therapy. In this regard some of the important findings from our study are in relation to the quality and duration of remis- sions. Although it is possible to achieve second and subsequent remissions with repeated lines of treatment, patients prefer to have durable remissions without the requirement for further therapy. We have shown that the patients in whom a CR is achieved, at any line of therapy, have longer DFS than those who only attained a PR. In relation to choice of purine analog we have no evidence from our data that there are any differences in outcome between patients treated with pentostatin or cladribine. The choice of agent rests therefore with the patients and their treating clinician. For ease of administration, cost-effective- ness, and lack of infusional and other side effects (e.g. nausea), subcutaneous cladribine has many advantages. Since the introduction of purine analogs nearly 30
years ago the incidence of deaths related to HCL in our series has been less than 4%. Only one HCL- related death has occurred in the last decade. This later improvement is mainly due to the better management of infections, particularly at presenta- tion, and the ability to salvage refractory patients with monoclonal antibody therapy. Many patients pre- senting in the mid-1980s who would have had a life- expectancy of around 4–5 years with conventional treatment are alive and disease-free today following treatment with purine analogs. The achievement of a CR is critical to this success and should be the goal of therapy at each stage.
Acknowledgements
Monica Else was funded by the Arbib Foundation. We would also like to thank E. Matutes, A. Wotherspoon, A. Morilla, R. Morilla, Nnenna Osuji, Juan Garcia-Talavera, Ama Z. S. Rohatiner, Steve A. N. Johnson, Nigel T. J. O’Connor, Andy Haynes, Francesco Forconi, Francesco Lauria, and all the other investigators who took part in this study.
Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at
www.informahealthcare.com/ lal.
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 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122