Hairy cell leukemia treated initially with purine analogs: a retrospective study of 107 patients from the Spanish Cooperative Group on Chronic Lymphocytic Leukemia (GELLC)

Abstract

Purine analogs are highly effective in hairy cell leukemia (HCL) with response rates of 85%, but with many late relapses. We have retrospectively reviewed the clinical data from 107 patients treated with pentostatin (n = 27) or cladribine (n = 80), to investigate the long-term efficacy and to identify factors associated with the treatment-free interval (TFI). Complete remission and minimal residual disease (MRD) rates were similar in both groups. Median TFI was shorter (95 vs. 144 months) in the pentostatin group, although the difference was not significant (p = 0.476). MRD+ patients had shorter TFI than MRD- patients (97 months vs. not reached, p < 0.049). A hemoglobin level < 10 g/dL predicted for a shorter TFI only in the pentostatin group. Quality of response and number of hairy cells in the bone marrow are independent risk factors of treatment failure. The relationship between MRD+ and shorter TFI makes it of special interest to explore consolidation therapy with monoclonal antibodies to achieve durable responses.

Long-term follow-up after purine analogue therapy in hairy cell leukaemia

“…These results have been confirmed by recent studies, all retrospective (Table 1), including long-term data from three earlier series: from the Scripps Clinic [37], from Bologna [18], and our own series, updated in 2009 [19], and reviewed in 2011 with a focus on the implications for clinical practice [15]. There are also two series, from Spain and France, with some minor overlap of patients from previous reports [38], [39] and three new reports from Turkey, India and Mexico [40], [41], [42]. Four of these studies report results with both cladribine and pentostatin, while the other four report only cladribine.…”

“…This led to a CR in 14 patients (78%) [15]. Similarly, in the Spanish series 8 patients in PR were treated with a second cycle of cladribine, which led to a CR in 6 patients (75%) [38]. In the Indian series 2 patients received a second cycle of treatment at 6–8 months and both achieved a CR [41].…”

“…eval. 2nd line patients2nd line ORR %2nd line CR%2nd relapse % (after CR/PR)% 2nd malignanciesScripps Clinic USAa (pts aged ≤40 y only)Rosenberg et al., 2014 [37]Cladribine831008825151 (CR)80 (PR)279644–9 (after)Bologna, Italye , aZinzani et al., 2010 [18]Pentostatin10967710544588.573.564–Cladribine7541Royal Marsden Hospital UKa , bElse et al., 2009 [19]Pentostatin18896821724426d9769c(median RFS 129 m)1 (before)12 (after)Cladribine4510076c1083858dSpain (GELLC)aLopez et al., 2014 [38]Pentostatin271009214551–––––Cladribine8010088c6325–––––France multicentreaCornet et al., 2014 [3...…”

“…Three large series which included both agents, from France, Spain and the UK, found no difference in ORR or CR rates between pentostatin and cladribine [19], [38], [39]. The Italian series included both agents, but did not analyse the results separately [18].…”

Hairy cell leukemia: Past, present and future

“…MRD was initially quantified using immunohistochemistry markers, and was identified in 13–26% of patients following treatment with pentostatin or cladribine [9]. More sensitive tests including flow cytometry and PCR for immunoglobulin gene rearrangement using consensus or sequence specific primers demonstrate MRD in 27–50% of patients who are in CR [10, 11]. Application of digital PCR found that all patients treated with vemurafenib had detectable MRD by quantification of mutant BRAF in bone marrow despite being in CR [12].…”