T-Cell Large Granular Lymphocyte Leukemia. A Report on the Treatment of 29 Patients and a Review of the Literature

570 T-Cell Large Granular Lymphocyte Leukemia A Report on the Treatment of 29 Patients and a Review of the Literature Nnenna Osuji, MBChB, MSc1 Este...
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T-Cell Large Granular Lymphocyte Leukemia A Report on the Treatment of 29 Patients and a Review of the Literature

Nnenna Osuji, MBChB, MSc1 Estella Matutes, MD, PhD1 Geir Tjonnfjord, PhD2 Henri Grech, MBBS3 Ilaria Del Giudice, MD1 Andrew Wotherspoon, MBBCh4 John G. Swansbury, BSc1 Daniel Catovsky, MD, DSc1

BACKGROUND. To the authors’ knowledge, there is no standard treatment for patients with T-cell large granular lymphocyte (LGL) leukemia. Available data are limited by patient numbers and coexisting pathologies. METHODS. The authors report on the use of immunosuppressants (cyclosporin A [CSA] and low-dose oral methotrexate [MTX] given continuously) and cytotoxic agents in the treatment of 29 patients with T-cell LGL leukemia age over the past 20 years.

RESULTS. The overall response rate (ORR) to MTX (n ¼ 8 patients) was 85.7% (complete hematologic response [CHR] rate, 14.3%; partial response [PR] rate,

1 Institute of Cancer Research, London, United Kingdom. 2 Department of Medicine, Rikshospitalet University Hospital, Oslo, Norway. 3

Department of Haematology, Royal Berkshire Hospital, Reading, United Kingdom. 4 Department of Histopathology, Royal Marsden Foundation Trust Hospital, London, United Kingdom.

71.4%) with dose-dependent responses observed and safe usage of doses >10 mg/m2 per week in 2 patients. The ORR to CSA (n ¼ 23 patients) was 78.2% (CHR rate, 30.4%; PR rate, 47.8%). The median time to response for both agents was 1 month. Toxicity, although it was minor in most patients and was more common in the CSA group, included second malignancies in 5 patients. An ORR of 67% (all CHR) was attained with pentostatin (n ¼ 4 patients); recurrences developed after a median of 4.6 years. Successful retreatment with pentostatin was possible but with increasing drug resistance. Cyclophosphamide induced CHR that lasted >7 years with bone marrow clearance in 1 of 4 patients. Alemtuzumab induced a PR in 1 patient who had refractory disease. CONCLUSIONS. Both MTX and CSA were efficacious in the treatment of T-cell LGL leukemia but generally required long-term maintenance therapy. The authors highlight the risks of second malignancies and persistence of bone marrow disease. Although MTX and CSA were effective as first-line therapy, alemtuzumab and pentostatin merit further investigation, particularly for refractory disease. Cancer 2006;107:570–8.  2006 American Cancer Society.

KEYWORDS: T-cell large granular lymphocyte leukemia, methotrexate, cyclosporin A, pentostatin, cyclophosphamide.

Dr. Nnenna Osuji was funded by a grant from the Arbib Foundation. We are grateful to the many clinicians who have referred patients and/or samples over the years. Address for reprints: Nnenna Osuji, MBChB, MSc, Section of Haemato-Oncology, Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom; Fax: (011) 44 2087224266; E-mail: nnenna.osuji@ icr.ac.uk Received January 6, 2006; revision received March 9, 2006; accepted March 27, 2006.

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-cell large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of clonal CD3-positive cytotoxic T cells that was described first by Brouet et al.1 and defined by McKenna et al.2 The median age ay onset is 55 years with equal gender distribution. One-third of patients are asymptomatic.5 Clinical manifestations usually are because of neutropenia with recurrent infections and mouth ulcers. Eighty-five percent of patients are neutropenic,6 with severe neutropenia (

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