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Hairy Cell Leukemia
By Jerome W. Yates, MD, Vice President for Research (Emeritus), American Cancer Society, Senior Scientist, National Institute on Aging, NIH. Dr. Yates reports no financial relationship relevant to this field of study.
A 51-year-old man was brought to the emergency department with severe abdominal pain and hypotension. He had no known chronic medical disease but for the past few months had experienced a loss of appetite, weakness, and fatigue. Despite these symptoms, he had not missed work (electrical engineer). Over the six months, his weight had fallen from 190 to 175 pounds. He did not recall night sweats or fever, but did mention that he experienced a loss of appetite and occasional nausea. On two occasions during the prior week, he vomited.
Upon presentation to the emergency room, he was noted to have severe abdominal pain, particularly on the left side, was markedly pale, and there were petechiae over his trunk and upper and lower extremities. Blood pressure was palpable at 60 mm Hg (systolic), and his pulse was 140 and regular. His abdomen was distended, and bowel sounds were absent.
Laboratories revealed his hemoglobin was 6.3 g/dL, total white blood count was 1,500/uL, and platelet count was 45,000/uL. Computerized tomography obtained in the emergency room demonstrated an enlarged spleen, with apparent extravasation of contrast raising the likelihood of splenic rupture.
The patient was taken to the operating room where an enlarged spleen (850 gm) with two focal lacerations was removed. There was approximately 1,100 cc of free blood within the abdominal cavity. Post-operative management was uneventful, and he was discharged on the 20th hospital day. At that time, his hemoglobin was 11.1 g/dL, WBC 3,800/uL, and platelet count 220,000/uL.
Pathology of the spleen revealed changes consistent with hairy cell leukemia (HCL), with diffuse involvement throughout the red pulp and, to a lesser extent, the white pulp. Peripheral blood immunophenotyping revealed the characteristic pattern of HCL (CD11c, CD25, CD103, CD123 and CD20). A bone-marrow biopsy obtained approximately one week prior to discharge revealed a generally fibrotic and hypocellular marrow with an infiltration of mononuclear cells that stained brightly with anti-CD20. The patient was referred for management of hairy cell leukemia.
Although, historically, splenectomy was the initial treatment for many patients with HCL, the success of current chemotherapeutic approaches precludes such an approach in the great majority of cases. Of course, in this case, surgery was life-saving and an effective initial treatment for his disease. The patient was fortunate to receive such prompt and aggressive management. From the data, as presented above, no immediate additional therapy would be warranted. Instead, the patient should be carefully followed with the expectation that, down the road, treatment will be required. Currently, there are no data that would indicate early intervention in cases such as this, or for patients with minimal residual disease (MRD), which translates to longer survival.
Before considering HCL-specific treatments, it is important to recognize that patients without a spleen are susceptible to bacterial infection and sepsis, and a strategy for vaccination and prophylactic antibiotics should be defined.1
The timing for initiating chemotherapy is not well established but, typically, intervention is warranted coincident with progressive cytopenias or the appearance of constitutional symptoms. Keeping in mind that the standard initial approach involves the use of purine nucleoside analogs, which themselves can be associated with granulocytopenia, treatment should begin before the granulocyte count falls to levels much below 2000/uL. Just as there is no consensus regarding the time to start therapy, there is none regarding initial treatment, other than the use of drugs in the purine nucleoside analog class and the need to attain a complete remission. The largest experience is with cladribine, and when administered by continuous infusion over seven days (0.1 mg/kg per day), complete remissions have been reported in over 90% of cases.2,3 Comparable responses also have been observed in patients treated on intermittent schedules (e.g., daily dose for five days or weekly dose for six weeks),4 or even when the drug is administered subcutaneously.5 Another commonly used, and most likely equally successful, purine nucleoside analog is pentostatin. Whereas the most substantial data for cladribine is with the initial seven-day infusion, pentostatin is typically administered on an interrupted schedule (e.g., every two weeks), which involves more frequent office visits and a more protracted treatment phase but offers the advantage of being able to adjust doses on the basis of blood counts and renal function, thereby minimizing the risk for protracted cytopenias.6
HCL cells typically express CD20, and there is current interest in exploring a role for rituximab, either with a purine nucleoside analog in patients with relapsed disease or as a single agent for patients with MRD.7,8 Also, interferon alpha is known to be effective, and newer immunological agents, such as the recombinant immunotoxins directed against CD25 (LMB-2) or against CD22 (BL22), hold promise for patients refractory to purine nucleoside analogs.
In summary, this patient was diagnosed with HCL at the time of emergency laparotomy for splenic rupture. Post-operatively, and for a yet-to-be defined period of time thereafter, he should be monitored closely. When the trajectory of his peripheral blood counts indicates impending risk, or as he develops constitutional symptoms, a purine nucleoside analog should be prescribed. In this case, in light of his prior health and presumably normal renal function, I would favor a single course of cladribine rather than a more protracted course of pentostatin, although the latter offers more fine tuning with regard to the aversion of protracted cytopenias and is the approach I would take in older or more impaired patients. The likelihood of success is high but, upon relapse, a number of active drugs and biologics are currently available and offer an excellent chance for durable second or even third remissions. There is no definitive proof that the disease is curable, and treatment, when asymptomatic with minimal disease, remains in the domain of clinical research.
1. Davies JM, Barnes R, Milligan D. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med. 2002;2:440-443.
2. Golomb HM. Hairy cell leukemia: Treatment successes in the past 25 years. J Clin Oncol. 2008;26:2607-2609.
3. Goodman GR, Burian C, Koziol JA, Saven A. Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol. 2003;21:891-896.
4. Robak T, et al. Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: Final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial. Blood. 2007;109: 3672-3675.
5. Lauria F, et al. Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications. Haematologica. 1999;84:22-25.
6. Grever MR. How I treat hairy cell leukemia. Blood. 2010;115:21-28.
7. Else M, et al. The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia. Cancer. 2007;110:2240-2247.
8. Thomas DA, Ravandi F, Kantarjian H. Monoclonal antibody therapy for hairy cell leukemia. Hematol Oncol Clin North Am. 2006;20: 1125-1136.