Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases

Abstract

BackgroundLarge granular lymphocyte leukemia is a rare lymphoproliferative disorder associated with autoimmune diseases and impaired hematopoiesis. This study describes the clinical and biological characteristics of 229 patients with T-cell or NK-cell large granular lymphocyte leukemia. Design and MethodsThe diagnosis was based on a large granular lymphocyte expansion (> 0.5¥10 9 /L) lasting more than 6 months. Monoclonal T-cell receptor γ gene rearrangement was detected in all the cases of T-cell large granular lymphocyte leukemia. Patients with chronic NK-cell lymphocytosis had an indolent disease, while those with multiorgan large granular lymphocyte infiltration and an aggressive clinical disease were considered to have NK-cell large granular lymphocyte leukemia. ResultsThe diagnosis of T-cell large granular lymphocyte leukemia was confirmed in 201 cases, chronic NK-cell lymphocytosis in 27 cases and NK-cell large granular lymphocyte leukemia in one case. Associated auto-immune diseases or other neoplasms were present in 74 and 32 cases, respectively. One hundred patients (44%) required treatment, mainly for neutropenia-associated infections (n=45), symptomatic auto-immune diseases (n =24), transfusion-dependant anemia (n=18), and other causes (n=13). Patients were treated with steroids (n= 33), methotrexate (n=62), cytoxan (n=32), or cyclosporine (n=24) either as first-, second-, third-or fourth-line therapy. The overall response rate at 3 months and complete response rate for the various treatments were as follows: steroids (12% and 3%), methotrexate (55% and 21%), cytoxan (66% and 47%), cyclosporine (21% and 4%), respectively. Four out of 13 patients responded to splenectomy. Eleven out of 15 patients responded to cytoxan after methotrexate treatment had failed. The mean number of treatments was 3.4 (range, 1-7). There were 15 large granular lymphocyte leukemia-related deaths. ConclusionsPatients with T-cell large granular lymphocyte leukemia and chronic NK-cell lymphocytosis have similar clinical and biological features and responses to treatment. First-line therapy with cytoxan should be tested in a prospective trial.Key words: large granular lymphocyte leukemia, LGL leukemia, NK lymphocytosis.Citation: Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, Schleinitz N, Tournilhac O, Roussel M, Fest T, and

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…T‐LGL leukemia is a rare condition within the spectrum of lymphoproliferative disorders on the interface between neoplasia and extensive antigen‐driven CTL response and is frequently associated with autoimmune disorders 98, 99, 100. According to this new study, the clinical criteria for an expanded LGL population in association to an autoimmune disorder101 were met in more than half of the 38 investigated IBM patients. Greenberg and colleagues controversially argue that, at least in some cases of IBM, an initial autoimmune process might transform into a neoplasia‐like condition with extensive clonal expansion of large granular CTLs resembling those of T‐LGL leukemia 97.…”

Białaczki z dużych ziarnistych limfocytów T i komórek naturalnej cytotoksyczności

“…Średni okres pojawienia się objawów od momentu postawienia diagnozy to 37 miesięcy, a średni czas przeżycia pacjentów z białaczką T--LGL przekracza 10 lat [18][19][20][21].…”

“…Największe opublikowane retrospektywne badanie Bareau i wsp. [20] obejmowało grupę 229 pacjentów leczonych w latach 1999-2007 w 35 ośrodkach we Francji. Przedstawiono w nim kliniczną i biologiczną charakterystykę pacjentów z białaczkami T/NK-LGL oraz wyniki odpowiedzi na zastosowane leczenie (opisane poniżej przy omawianiu poszczególnych rodzajów terapii).…”

“…[20] odsetek wszystkich odpowiedzi u chorych na T/NK-LGL leczonych MTX wynosił 55%, a czas do uzyskania odpowiedzi -2-12 tygodni. Niestety, u znaczące-go odsetka chorych obserwowano nawrót choroby w trakcie terapii, a neutropenia pojawiała się ponownie nawet u pacjentów, którzy uzyskali całkowitą remisję molekularną [20]. Czas leczenia MTX nie został zdefiniowany.…”

“…W badaniu Bareau i wsp. [20] łączny odsetek odpowiedzi był nawet większy niż w przypadku MTX i wynosił 65%. Warto odnotować, że 11 z 15 pacjentów, którzy nie zareagowali na leczenie MTX, uzyskało odpowiedź po podaniu Cy [20].…”