Infections and hairy cell leukemia Table I. Infections During Drug Treatment.
Infection and or
Drug
Pentostatin5–9 2-CDA10–14
Interferon15–17 Rituxan18–20
Patients 649
1444 339 49
neutropenic fever
188 495 74 1
Herpes Zoster Death
9 4 0 0
11 6 6 0
Although most patients went into remission, there were still 11 reported deaths during treatment. Besides the usual bacterial infections, there were nine cases of herpes zoster, usually in the few months post-treatment. In five series of 1444 patients who received cladribine (2-CDA) as initial treatment, there was a 32% incidence of infection or neutro- penic fever, with six reported deaths [10–14]. Herpes zoster was reported in four patients, but in several of these series there was not adequate reporting of infections or complications to compare with the results of penostatin trials. In four trials of interferon [5,15–17], 339 patients were reported, and here infections were significantly less, amounting to only 17% of patients with infection or neutropenic fever. In fact, in several studies no infections were seen and no reports of zoster were noted. The recent introduction of rituximab as treatment
has led some to be concerned about an increase in infections in treated patients. In a review of three series of 49 patients treated with rituximab as a single agent post-purine nucleoside therapy and with recurrent or refractory disease, only one neutropenic patient was reported as infected and no cases of herpes zoster were seen [18–20]. The frequency and severity of infections during
active disease is in sharp contrast to long-term follow- up of patients treated with the purine nucleosides. In over 500 patients in follow-up for 7 years, including three different clinical trials using pentostatin or 2- CDA, there were no significantly increased infections in patients in clinical remission [21–23]. Studies of immune defects after purine nucleosides showed recovery of neutrophils, monocytes, and natural killer activity, but long-term reduction of CD4 counts [4]. Even though the depression of CD4 counts remained low, there were no documented opportunistic infec- tions, as opposed to patients with these counts and human immunodeficiency virus (HIV). These investigations have taught us valuable
lessons about hairy cell leukemia and its manage- ment. First, clinicians should be vigilant in following patients with HCL and active disease, including during treatment. They need to aggressively work up and treat patients with fever and/or clinical symp-
51
toms. Second, continued evaluation of the infectious risk during treatment, and innovative therapy to prevent it, are necessary. The use of granulocyte- colony stimulating factor (G-CSF) and/or interferon is an example of prior attempts that have had variable success. G-CSF did not appear to make a difference in neutropenic patients on treatment [22], but inter- feron may have reduced the infectious risk on treatment [24]. Third, re-examination of the causes of infection in patients with HCL may afford a means of predicting who will develop infection and institu- tion of early interventions. Finally, long-term follow- up of treated patients for recurrent infection will demonstrate the safety of our current drugs and the importance of achieving remission in our patients. Arthur Clarke has alluded to new technology’s transformative power, and in the case of HCL our new treatment has ‘magically’ changed the natural history of this disease.
Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at
www.informahealthcare.com/lal.
References
1. GolombHM,Hadad L. Infectious complications in 127 patients with hairy cell leukemia. Am J Hematol 1984;16:393–401.
2. Stewart DJ, Bodey GP. Infections in hairy cell leukemia. Cancer 1981;15:801–805.
3. Bouza E, Burgeleta C, Golde DW. Infections in hairy cell leukemia. Blood 1978:51 851–859.
4. Dasanu CA, Ichim TE, Alexandrescu DT. Inherent and iatrogenic immune defects in hairy cell leukemia revisited. Expert Opin Drug Saf 2010;9:55–59.
5. Grever M, Kopecky K, Foucar MK, et al. Randomized comparison of pentostatin and interferon alpha-2a in pre- viously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 1995;4:974–982.
6. Maloisel F, Benboubker L, Gardembas M, et al. Long term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients. Leukemia 2003;17:45–51.
7. Catovsky D, Matues E, Talavera JG, et al. Long term results with 20deoxycoformycin in hairy cell leukemia. Leuk Lym- phoma 1994;14(Suppl. 1):109–113.
8. Rafel M, Cervantes F, Beltran JM, et al. Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients. Cancer 2000;88: 352–357.
9. Riberio, P, Bouaffia F, Peaud PY, et al. Long term outcome of patients treated with pentostatin. Cancer 1999;85:65–71.
10. Saven A, Burian C, Koziol JA, Piro LD. Long term followup of patients with hairy cell leukemia after treatment with cladribine. Blood 1998;92:1919–1926.
11. Hoffman MA, Janson D, Rose E, Rai KR. Treatment of hairy cell leukemia with cladribine response, toxicity and long term followup. J Clin Oncol 1997;15:1138–1142.
12. Cheson BD, Sorensen JM, Vena DA, et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer
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