Rituximab as treatment for minimal residual disease in hairy cell leukaemia

Abstract

Purine analogues have dramatically improved the outcome of patients affected by hairy cell leukemia (HCL), although complete eradication of disease was achieved in few cases. The purpose of this study was to evaluate the role of Rituximab in eradicating minimal residual disease (MRD) in HCL patients after a pre-treatment with 2-chloro-deoxy-adenosine (2-CdA). Ten patients received four cycles of Rituximab after administration of Cladribrine. Before starting anti-CD20 antibody, two patients were in complete remission, six in partial remission and two showed no significant response to Cladribrine. All cases resulted IgH-positive. Median time from the last 2-CdA infusion was 5.7 months. Eight of 10 patients [four in partial remission (PR), two in complete remission (CR) and two unresponsive after 2-CdA] were evaluable for response. Two months after the end of anti-CD20 therapy, all evaluated patients presented a complete haematological remission. Moreover, Rituximab increased percentage of molecular remission up to 100% 1 yr after the end of treatment. Interestingly, in all cases but one, including those persistently polymerase chain reaction (PCR)-positive, semi-quantitative molecular analyses showed MRD levels lower than those found before Rituximab administration. Toxicity was very mild. The present results not only confirm the therapeutic effect of Rituximab, but also show its relevance in eradicating MRD in HCL.

Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

“…Moreover, results are difficult to interpret because of the heterogeneity of the techniques and samples used for each patient. The low rate of MRD negativity we observe after rituximab (two of nine patients) may also be due to the fact that MRD evaluation was often performed quite early after treatment, whereas previously published data have shown that molecular responses increase over time and are still quite low at 2 and even 6 months [19,14].…”

“…For these patients, MRD was analyzed on a BM or PB sample using either immunophenotyping by flow cytometry or detection of an immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) [19,20].…”

Eradication of minimal residual disease in hairy cell leukemia

“…A different approach would be to evaluate the marrow for MRD at 3 to 6 months after the completion of therapy with cladribine and administer monoclonal antibody only to those patients with evidence of MRD as has been done by Cervetti et al 33 Alternatively, pretreatment features may be identified that would predict the likelihood of relapse, thereby allowing selection of appropriate patients for additional therapy.…”

Minimal Residual Disease in Hairy Cell Leukemia Patients Assessed by Clone-Specific Polymerase Chain Reaction

“…We reported that PCR of sequences encoding surface IgH using consensus primers was less sensitive than flow cytometry, the latter able to detect below one HCL cell in 10 4 normal cells (24). Capillary electrophoresis after fluorescent PCR using consensus primers allowed detection until one IgH + cell was diluted into 10 5 normal cells (21) and showed that MRD cleared in five of eight with CR, suggesting that rituximab might finally be an agent capable of eradicating HCL. We reasoned that assessing eradication of HCL would require even higher sensitivity PCR tests, previously reported for chronic lymphocytic leukemia and acute lymphoblastic leukemia.…”

“…Small clinical trials have reported a total of 18 (30%) CRs of 60 HCL patients (17 -20). Of eight HCL patients in CR after rituximab, five proved negative by PCR using consensus primers, a technique sensitive until one IgH-positive cell was diluted into 10 5 normal cells (21). BL22 is a recombinant immunotoxin containing truncated Pseudomonas exotoxin fused to the variable domains of an anti-CD22 monoclonal antibody, which induces CRs in 19 (61%) out of 31 purine analogue-resistant HCL patients (22,23).…”