Leukemia & Lymphoma, June 2011; 52(S2): 1–2 EDITORIAL
Treatment of Hairy Cell Leukemia in its Second Half-Century: An International Conference on Hairy Cell Leukemia at the National Institutes of Health, April 26–27, 2010, Bethesda, MD
ROBERT J. KREITMAN1, AARON POLLIACK2, & MICHAEL GREVER3
1Laboratory of Molecular Biology, NCI, NIH, Bethesda, MD, 2Department of Hematology, Hadassah University Hospital, Hebrew University Medical School Jerusalem, Israel, and 3Department of Medicine, Ohio State University Medical Center, Columbus, OH
Since the original description of hairy cell leukemia (HCL) in 1958 by Dr. Bertha Bouroncle, this fascinating disease, constituting 2% of all leukemias, has captivated the interest of many physicians, and researchers and continues to do so today. The long filamentous cytoplasmic projections, defined in detail in the early 1970’s by both transmission and scanning electron microscopy, give these cells and the leuke- mia a unique appearance. HCL was first treated effectively by splenectomy, and later in the 1980s interferon was reported as the first effective systemic therapy for this disease. Later in that same decade, a substantial breakthrough came from the development of purine analogs. These included 2-deoxycoformy- cin (DCF, pentostatin) and 2-chlorodeoxyadenosine (CdA, cladribine), which revolutionized the treat- ment of HCL. Either pentostatin given once every two weeks by an intravenous short infusion, or cladribine, given in a single 5 to 7 day course, enabled 70–90% of the patients to achieve complete remission, with 7–8 year disease-free survivals of 60– 75%. Large studies documented excellent response and safety profiles. A randomized comparison showed clear superiority of pentostatin over inter- feron and a variety of investigators around the world confirmed the activity and safety of purine analogs. Gradually, treatment of HCL patients moved from the large referral centers of universities to the infusion centers of local physicians, and patients were often informed that they were cured and would not have to be concerned about their disease in the future. In the past 20–25 years since the advent of purine
analogs for HCL, no new agents have been approved for HCL, but along with this the expected plateaus
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.552478
on the disease-free survival curves were not forth- coming. Instead, relapse of HCL occurred at a rather constant rate, and although excellent results could be consistently attained with second line purine analog, remissions rates were statistically lower with repeated courses of these drugs, and long-term toxicity to the
immune system, particularly CD4þ lymphocytes, accumulated. Furthermore, improved techniques to detect minimal residual disease (MRD) documented the presence of hairy cells in a surprisingly high percentage of patients considered to be in complete remission. Although a small number of patients have been indentified without MRD a median of 16 years after cladribine, and MRD may not always lead to clinical relapse, it has become increasingly clear that HCL is not entirely a ‘beaten’ disease. Because HCL cells comprising MRD remain strongly positive for CD22 and CD20, recombinant immunotoxins tar- geting CD22 and rituximab targeting CD20 were tested as therapy and found to be active. In fact, it has been suggested that monoclonal antibody thera- pies could possibly eradicate HCL cells in some patients, when used either alone or in combination with purine analogs. How best to incorporate monoclonal antibody therapy into the treatment of early and relapsed HCL still remains undefined, and clinical trials are underway to explore several options.
Attempting to address unfinished challenges
relating to this chronic disease, we organized an international meeting of HCL experts, the first in many years and the first ever at the NIH. The meeting was made possible by the NIH Office of Rare Disease Research, the Center for Cancer Research of the NCI, and generous donations from
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