Long‐term follow‐up of patients with hairy cell leukaemia treated with pentostatin: lymphocyte subpopulations and residual bone marrow infiltration

Abstract

Peripheral blood lymphocyte (PBL) subsets and bone marrow biopsies were analysed in six patients with hairy cell leukaemia (HCL) treated with 2'-deoxycoformycin (pentostatin, DCF) according to a phase II trial of the EORTC Leukemia Cooperative Group. All patients responded to DCF with four complete and two partial remissions according to conventional criteria. Within the PBL subsets, major changes concerned the CD4+ T cells, which during DCF therapy were distinctly suppressed to nadir values of 0.038-0.18 (median 0.126) x 10(9)/l. In five patients these cells returned to normal 3.0-49.5 (median 14.5) months after the last DCF injection. CD8+ cells were decreased to a lesser extent, and NK cell numbers improved during treatment. Bone marrow immunohistology applying the MoAb B-ly7 demonstrated residual hairy cells (HCs) in all of the six patients following DCF treatment with nadir HC numbers of 0.2-3.0% of bone marrow cells. Immunoglobulin gene rearrangement analysis of DNA obtained from these biopsies showed only germline bands, whereas rearranged bands had been present on the pretreatment specimens. Within the observation period of 15.5-54.0 (median 47.0) months after discontinuation of DCF therapy, immunohistology demonstrated a continuous increase in HC numbers in five of the six patients with clonal rearrangement detectable in bone marrow specimens from three of these patients at last follow-up date. Although established on the basis of a small number of patients, these data suggest that DCF treatment as currently employed in HCL is unable to eradicate the malignant B cell clone.

Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-α-resistant hairy cell leukemia: 7-year follow-up

“…This depth of CD4 + lymphocytopenia is comparable to the median nadir values of 126/l (range 38 References to 180/l) and 54/l (range 11 to 203/l) reported previously following DCF. 20,21 These values also appear very similar to…”

“…Our data demonstrate that with a median follow-up beyond 7 years and in spite of resistphocytopenia following treatment with DCF. [17][18][19][20][21] In the current study, despite normal pre-therapy CD4…”

“…After DCF, nadir CD4 + and CD8 + lymphoconsequences of the long-term immunosuppressive effects of cyte counts were significantly lower than prior to therapy (P Ͻ Ͻ Ͻ 0.0001 and P = 0.05, respectively), but returned to baseline DCF, particularly on T cells. [17][18][19][20][21] To address these issues, we levels during follow-up. Median times to attainment of the lower have examined the duration of remission, survival, long-term limit of the normal range of CD4 + and CD8 + lymphocytes were complications, and kinetics of recovery of CD4 + lymphocytes 54 and 36 months, respectively.…”

The significance of minimal residual disease in hairy cell leukaemia treated with deoxycoformycin: a long‐term follow‐up study

“…Studies describing MRD in HCL have addressed mainly the effect of IFN or CDA, but few have investigated MRD after treatment with DCF (Thaler et al, 1990(Thaler et al, , 1993. A summary of the studies documenting MRD in HCL is shown in Table IV.…”

“…Several studies have addressed this issue by examining the possible role of immunological markers or DNA analysis to detect residual hairy cells (Di Celle et al, 1994;Ellison et al, 1994;Filleul et al, 1994;Foa et al, 1990;Hakinian et al, 1993;Pileri et al, 1994;Thaler et al, 1990Thaler et al, , 1993Wheaton et al, 1996). These studies have focused mainly on monitoring disease status during treatment (Ambrosetti et al, 1989;Thaler et al, 1990;Foa et al, 1994) and few have been done after stopping treatment with IFN, CDA and, rarely, DCF (Di Celle et al, 1994;Ellison et al, 1994;Filleul et al, 1994;Hakinian et al, 1993;Pileri et al, 1994;Wheaton et al, 1996;Thaler et al, 1993). The follow-up in most of these series has been relatively short and, considering the low proliferative rate of HCL, relapses may become apparent after a long period of time following remission.…”