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Treatment of T-cell large granular lymphocytic leukaemia the role for methotrexate and cyclosporine A in new, relapsed and refractory cases

Treatment of T-cell large granular lymphocytic leukaemia the role for methotrexate and cyclosporine A in new, relapsed and refractory cases

Blood 102(11): 404a, November 16

Large granular lymphocytic (LGL) leukaemia is a malignant proliferation of CD3+ cytotoxic T cells (T-LGL) or rarely, CD3- natural killer cells (NK-LGL). One third of cases are asymptomatic at diagnosis. Symptomatic neutropenia is the most common indication for treatment. A variety of modalities have been used to treat LGL leukaemia. Responses and criteria for response have been variable. Importantly eradication of the clone and/or complete normalisation of the blood count may not be necessary. Treatment with low dose oral methotrexate (MTX) has been reported with complete response (CR) in the blood in 60% of patients, and molecular CR in 50% of these (Loughran et al, Blood; 1994). Since this report, no study has focused on this treatment. Additionally, few reports address the impact of treatment on the bone marrow. We reviewed records from 13 patients with LGL leukaemia (12 T-LGL, 1 NK-LGL) treated at the Royal Marsden Hospital. CR was defined by a normal blood count and absence of organomegaly, partial response (PR) by an improvement in organomegaly and cytopenia by >/=50% and good PR (GPR) if neutrophils were >1.0X109/l. Improvements short of PR were termed minimal response (MR). Bone marrow criteria have not been included in definitions of response in this or other reported series. Five patients were treated with once weekly MTX. All five responded with CR in 1, GPR in 3 and PR in 1. MTX was used as first line treatment in 2 cases. Maximum responses have not yet been achieved in most. Bone marrow biopsies were assessed pre and post treatment in 2 patients (1 CR and 1 GPR). Despite responses in the peripheral blood, no marked difference in degree of infiltration was observed in the bone marrow. MTX induced responses despite failure of multiple previous therapies (up to 8 in one case) including stem cell transplantation. Mean time to PR was 1.1 month with median follow up of 16.9 months (range 8-27). Despite low doses of <10mg/m2/week in 3 patients, responses were still induced with CR in 1 patient. Improved responses were induced in 2 patients by increasing the dose to >10mg/m2/week. No serious adverse events were observed. Oral cyclosporine A (CSA) was used in 6 patients (first line therapy in 4) of whom 5 were evaluable yielding 1 CR, 2 GPR, 1 PR and 1 MR. Bone marrow biopsy features showed no evidence of residual infiltration by morphology, immunohistochemistry and PCR for T cell gene rearrangement in the only patient achieving CR. Mean time to PR was longer than MTX (3.95 months; range 0.75-13). Hypertension and headaches were reported in 2 patients. We confirm the efficacy and safety of low dose MTX and CSA in treatment of patients with LGL leukaemia. MTX may have a role in resistant cases and may show a dose dependent effect. Doses above the reported 10mg/m2/week may be safely used.

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Accession: 035980625

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