EurekaMag.com logo
+ Site Statistics
References:
53,623,987
Abstracts:
29,492,080
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

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.

(PDF 0-2 workdays service: $29.90)

Accession: 035980625

Download citation: RISBibTeXText



Related references

Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis. British Journal Of Haematology. 93(2): 406-408, 1996

Moderate-dose cyclophosphamide in the treatment of relapsed/refractory T-cell large granular lymphocytic leukemia-associated pure red cell aplasia. Hematology 21(3): 138-143, 2016

Resolution of transfusion-dependent anemia in patients with refractory large granular lymphocytic leukemia following treatment with cyclosporine A. Blood 84(10 SUPPL 1): 460A, 1994

Efficacy and safety of long-term (>7 year) alemtuzumab therapy for refractory T-cell large granular lymphocytic leukaemia. British Journal of Haematology 150(4): 480-481, 2010

Phase I/II evaluation of pentostatin (2'-deoxycoformycin) in a five day schedule for the treatment of relapsed/refractory B-cell chronic lymphocytic leukaemia. Investigational New Drugs 16(2): 155-160, 1998

Efficacy of alemtuzumab treatment for refractory T-cell large granular lymphocytic leukemia. Blood 103(5): 1969-1971, 2004

Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia. Health Technology Assessment 14(Suppl. 2): 19-26, 2011

Successful treatment of refractory pure red cell aplasia secondary to chronic lymphocytic leukaemia with cyclosporine A: correlation between clinical and in vitro effects. Nouvelle Revue Francaise D'hematologie 36(4): 307-309, 1994

Chemotherapy of mantle cell lymphoma relapsed or refractory chronic lymphocytic leukaemia. Prescrire International 25(170): 91-91, 2016

Lessons from a case of T-cell large granular lymphocytic leukaemia suggesting that immunomodulatory therapy is more effective than intensive treatment. Leukemia Research 29(2): 225-228, 2004

A case of ALK negative anaplastic large cell lymphoma with leukaemic manifestation, transformed from CD4 positive T-cell large granular lymphocytic leukaemia. Pathology 47(1): 86-87, 2015