THE SCRIPPS-CLINIC EXPERIENCE WITH 2-CHLORODEOXYADENOSINE IN THE TREATMENT OF HAIRY-CELL LEUKEMIA

Follow-up data is now available on 144 patients with hairy cell leukem ia treated with 2-chlorodeoxyadenosine (2-CdA) at the Scripps Clinic. Of 144 patients followed for a median of 14.2 months, 123 (85%) obtain ed complete responses, 17 (12%)partial responses, 3 (2%) did not respo nd and 1 patient was unevaluable. So far, only 4 patients have relapse d at a median of 36 months. Fever was the major toxicity occurring in 43% of patients. Five patients resistant (3 patients) or intolerant (2 patients) to 2'-deoxycoformycin were also treated. Of these 5 patient s, 4 obtained complete responses, including 2 patients resistant to 2' -deoxycoformycin, and 1 patient a partial response, suggesting a possi ble lack of cross-resistance between 2'-deoxycoformycin and 2-CdA in h airy-cell leukemia. More than 200 patients have been treated with 2-Cd A worldwide with 82% obtaining complete remissions and 12% partial rem issions. Serial peripheral blood immunophenotypic analyses have docume nted the absence of circulating hairy cells. When bone marrow biopsies were examined using sensitive immunohistochemical staining techniques , residual hairy cells were detected in 25-50% of morphologic complete responders. Patients will need to be observed longitudinally to deter mine if this staining is predictive of relapse. A double-blind, placeb o-controlled study of pentoxifylline, a modulator of tumor necrosis fa ctor-alpha and other cytokines, was performed in 2-CdA-treated hairy c ell leukemia patients to determine whether the incidence of neutropeni c fever would be reduced. Although pentoxifylline resulted in less feb rile, hospital and antibiotic therapy days than placebo, only the numb er of days in the hospitalized patients achieved statistical significa nce. 2-CdA is emerging as the treatment of choice for hairy cell leuke mia given the high percentage of long-lasting, complete responses that follow a single course of therapy.