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 leukemia 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-deoxycoformycin (DCF, pentostatin) and 2-chlorodeoxyadenosine (CdA, cladribine), which revolutionized the treatment 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 interferon 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 on the disease-free survival curves were not forthcoming. 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 CD4+ 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 targeting CD22 and rituximab targeting CD20 were tested as therapy and found to be active. In fact, it has been suggested that monoclonal antibody therapies 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 the Hairy Cell Leukemia Consortium. The Hairy Cell Leukemia Research Foundation, which has supported HCL research for many years, was also represented at the meeting. The goals of the meeting were to 1) discuss standard treatments of HCL and evidence supporting their administration, 2) determine needs and current and future opportunities for clinical research, 3) disseminate results of newer diagnostic techniques, 4) discuss recent advances in HCL biology, including the molecular characterization of HCL cells with implications for disease origin and prognosis, 5) discuss new treatments for relapsed and refractory disease, including investigational agents, and 6) improve patient access to treatment and clinical trials. The meeting took place on April 26–27, 2010 on the NIH campus and the program of this meeting is included in this issue of the journal. Many of the speakers who discussed HCL topics contributed a short version of their talks in a summary for this issue of Leukemia and Lymphoma.
It is our combined hope that renewed energy from this conference will lead to continuing basic and clinical research in this disease, stimulate the development of new strategies for improving the very long-term outcome of patients and encourage international co-operation in HCL worldwide. We look forward to progress in this field and hope that these workshops in HCL will become a permanent feature on our calendars in the years to come.
Robert Kreitman
Aaron Polliack
Michael Grever