Complete Eradication of Minimal Residual Disease (MRD) in Patients with Hairy Cell Leukemia (HCL) after Cladribine (2CDA) Followed by an Extended Course of Rituximab.

The nucleoside analogs 2CDA and pentostatin are effective in the initial therapy of patients with HCL, but relapses are common. We have investigated whether an 8 week course of therapy with weekly rituximab after 2CDA can eradicate MRD assessed by flow cytometry as well as by immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) assay using framework-1, -2 and -3 primer sets. Treatment constituted 2CDA 5.6 mg/m² IV given over 2 hours daily for 5 days. One month after initiation of 2CDA, bone marrow (BM) MRD was assessed and rituximab 375 mg/m² IV was given weekly for 8 weeks. BM MRD was reevaluated again after the completion of rituximab. To date, 12 patients have been treated including 10 with newly diagnosed disease and 2 after relapse from prior therapy (2CDA in one patient and chlorambucil in another). The median age of the patients was 55 years (range 31–73). Two patients had variant HCL. Fluorescent in situ hybridization (FISH) was positive for the presence of a clone with p53 deletion/monosomy 17 in 2 patients. One patient with variant HCL had complex cytogenetics. Seven of 10 evaluable patients had mutated IgVH gene whereas IgVH was unmutated in 3 patients. All 12 patients (100%) have achieved CR defined as no hairy cells in BM and blood with normalization of counts (ANC >1.5 x 10⁹/L, Hgb >12.0 g/dL, Plt > 100 x 10⁹/L) after completion of all therapy; 5 patients still had 1% to 50% hairy cells in BM after 2CDA therapy. MRD by flow was positive in 11 patients after 2CDA therapy but became negative in all 12 patients after rituximab. MRD by PCR was positive in 5 of 10 evaluable patients after 2CDA therapy and became negative in 10 of 11 evaluable patients (equivocal in 1) after rituximab. With a median duration of follow-up of 11 months (range 3–13) no patients have relapsed (median response duration 6+ months, range 1–13). One patient has developed a second cancer (pancreatic). We conclude that therapy with an extended course of rituximab is effective in eradicating MRD in HCL. The predictive value of achievement of negative MRD, presence of chromosome 17 abnormalities, or the mutational status of IgVH on the risk of relapse should be evaluated in larger series and with longer follow-up.