Very long-term eradication of minimal residual disease in patients with hairy cell leukemia after a single course of cladribine.

Cladribine induces protracted remissions in patients with hairy cell leukemia (HCL). However, many long-term responders ultimately relapse. We sought to determine whether long-term complete responders subsequent to a single 7-day course of cladribine were without minimal residual disease (MRD) and potentially cured of HCL. From the 358-person Scripps Clinic cladribine database, we identified 19 patients in continuous and complete hematologic response (median age, 75 years; median time from diagnosis, 18 years; and median time from cladribine, 16 years). Nine of 19 (47%) patient samples had no evidence of residual disease; 7 of 19 (37%) samples had MRD; and 3 of 19 (16%) had morphologic evidence of HCL in hematoxylin and eosin-stained bone marrow sections. These results indicate that HCL is potentially curable after cladribine treatment. In addition, patients with MRD and even gross morphologic disease can live many years without manifesting hematologic relapses.

How I treat hairy cell leukemia.

The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of alpha-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed this disease into a highly treatable form of leukemia, and patients with the classic form of this rare leukemia now have a near-normal life expectancy. However, other clinical entities mimicking this disease do not respond; thus, accurate diagnosis is important. Immunophenotypic features in classic hairy cell leukemia show that the leukemic cells express CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high percentage of durable complete remissions with modern therapy, the long-term disease-free survival curves have not reached a plateau. Many patients who achieve a complete remission by morphologic criteria have minimal residual disease demonstrable by either flow cytometry or immunohistochemical staining, and this population may be at higher risk for earlier relapse. Continued clinical research is essential to optimize therapy for this disease.

Eradication of minimal residual disease in hairy cell leukemia.

Although the nucleoside analogs cladribine and pentostatin produce high response rates in patients with hairy cell leukemia (HCL), a significant number of patients eventually relapse. Several studies have demonstrated that patients with complete remission (CR) have a longer disease-free survival. Therefore, strategies to improve on the initial response to nucleoside analog therapy are likely to be beneficial, at least for a proportion of patients. We have treated 13 patients with newly diagnosed HCL (n = 11) or after failure of one prior chemotherapy (n = 2) with cladribine (5.6 mg/m(2) given intravenously over 2 hours daily for 5 days) followed by 8 weekly doses of rituximab (375 mg/m(2)). All patients achieved a CR and minimal residual disease (MRD) assessed by consensus primer polymerase chain reaction (PCR) or flow cytometry was eradicated in 11 (92%) of 12 and in 12 (92%) of 13 of patients, respectively. There was no decline in the absolute CD4 and CD8 lymphocyte number after rituximab. We conclude that eradication of MRD in HCL is possible. Whether this leads to a reduced risk of relapse would need to be evaluated in a larger number of patients and with longer follow-up. Disease characteristics may potentially be used to identify patients that are more likely to benefit from such additional therapy.

Chimeric monoclonal anti-CD20 antibody (rituximab)--an effective treatment for a patient with relapsing hairy cell leukaemia.

A case story is presented, describing a 46 y old man, with a relapsing hairy cell leukaemia. After treatment with monoclonal anti CD-20 antibodies (rituximab) 375mg/week, four times, a complete remission was obtained which has lasted >9 months. The rituximab treatment produced a better remission than earlier treatments with alpha-interferon and chlorodeoxyadenosine. In addition, in contrast to other treatments, no initial worsening of the pancytopenia was observed.

Minimal residual disease in patients with hairy cell leukemia in complete remission treated with 2-chlorodeoxyadenosine or 2-deoxycoformycin and prediction of early relapse.

The purine nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) induce complete remission (CR) in the majority of patients with hairy cell leukemia. However, minimal residual disease (MRD) has been detected in bone marrow core biopsies using immunohistochemical techniques in patients achieving CR by conventional criteria. This study was designed to compare the prevalence of MRD with each agent in patients in CR by using conventional criteria and the relapse-free survival for patients with and without MRD. Bone marrow biopsies from 39 patients treated with a single cycle of 2-CdA and 27 patients treated with multiple cycles of 2'-DCF were studied. The monoclonal antibodies anti-CD20, DBA.44, and anti-CD45RO were used to evaluate the paraffin-embedded bone marrow core biopsies for MRD. Five of 39 patients (13%) treated with 2-CdA had MRD, as compared to 7 of 27 patients (26%) treated with 2'-DCF (two-tailed P = 0.21). Relapse has occurred in two of the five patients with MRD after 2-CdA treatment and in four of the seven patients with MRD after 2'-DCF treatment. In total, 6 of the 12 patients (50%) with MRD have relapsed, whereas 3 of 54 patients (6%) without MRD have relapsed, and 2 patients have died without evidence of relapse. The estimated 4-year relapse-free survival among patients with MRD is 55% (+/- 15%, SE), compared to 88% (+/- 5%, SE) among patients without MRD (two-tailed P = 0.0023). The prevalence of MRD detected in a subset of patients in CR after either 2-CdA or 2'-DCF treatment did not differ significantly. However, the presence of MRD is associated with an increased risk of relapse.