Large granular lymphocyte leukemia: natural history and response to treatment

Abstract

Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.

How I treat LGL leukemia

“…These results were confirmed in further series, and MTX has been mainly proposed as first-line therapy. 59,65,69 In a larger series of 62 patients, we recently demonstrated that the 55% overall response rate was slightly lower than that reported in the limited series and that a significant proportion of patients relapsed on therapy. Indeed, 12 of 18 patients (67%) followed more than one year relapsed, raising the question of the long-term efficacy of such treatment.…”

“…12,65,69,[76][77][78][79][80][81][82] The overall ORR indicates overall response rate; CHR, complete hematologic response; -, not applicable; PRCA, pure red cell aplasia; and CR, complete response. *A total of 50-100 mg/day or 250-500 mg intravenously.…”

“…12,13,[65][66][67]69,[72][73][74][75] Response rates vary from one study to another and are usually better in the small series. Patients with pure red cell aplasia appear to have a good response.…”

Białaczki z dużych ziarnistych limfocytów T i komórek naturalnej cytotoksyczności

“…Metotreksat (MTX, methotrexate) jest lekiem I linii w białaczce T-LGL; zalecana dawka to 5-10 mg/m² powierzchni ciała raz w tygodniu [41,69]. W badaniu Bareau i wsp.…”

“…Jednak większość autorów proponuje CsA jako II linię leczenia, ponieważ nie powoduje ona eradykacji komórek białaczkowych. Odsetek odpowiedzi jest bardzo różny w poszczególnych badaniach i nierzadko w trakcie terapii dochodzi do utraty odpowiedzi [20,40,41,69,[71][72][73].…”