A total of 96 patients with T-LGLL including 49 males and 47 females were identified (details in supplementary table S1). The median age was 59 years old(range: 28-89 years old). The baseline clinicopathologic characteristics were showed in Table 1. At the time of presentation, 71 patients (71/96, 74.0%) had symptoms, while fatigue was the most common one (53/96, 55.2%). In our cohort, only 4 cases (4/94, 4.2%) had rheumatoid arthritis. The median large granular lymphocytes count was 2.94×109/L (range: 0.2-19.75×109/L). Neutropenia, thrombocytopenia and anemia were found in 49 (51.0%), 16 (16.7%), and 53 (55.2%) cases, respectively. A total of 26 patients were confirmed to have PRCA by bone marrow examination. TCR clonal rearrangement was confirmed in all cases. STAT3 sequencing was performed in 64 patients, in which 7 patients had STAT3 mutations.
Table 1
Clinical, laboratory, and molecular features of 96 patients with T-cell large granular lymphocytic leukemia.
Parameters | Na (%)* |
Gender | |
Male | 49 (51.0) |
Female | 47 (49.0) |
Age | |
≥60 years | 45 (46.9) |
<60 years | 51 (53.1) |
Fatigue | 53 (55.2) |
B symptoms | 16 (16.7) |
Infection | 11 (11.5) |
Large granular lymphocyte count (⋅109/L) | 2.94 (0.27-19.75) |
Absolute lymphoctye count (⋅109/L) | 3.71 (0.52-23.03) |
Absolute neutrophil count (⋅109/L) | 1.53 (0.21-9.18) |
Hemoglobin (g/L) | 88.5 (32-165) |
Platelet count (⋅109/L) | 179.5 (11-465) |
Absolute neutrophil count ≤1.5 × 109/L | 49 (51.0) |
Absolute neutrophil count≤0.5 × 109/L | 9 (9.4) |
Hemoglobin ≤100 g/L | 53(55.2) |
Platelet count ≤100 × 109/L | 16 (16.7) |
Lactate dehydrogenase ≥271 U/L | 13 (13.5) |
β2-microglobulin ≥2.53 mg/L | 62 (64.6) |
Ferritin ≥336.2 ng/ml | 38(39.6) |
Splenomegaly | 22 (22.9) |
Hepatomegaly | 4 (4.2) |
Lymphadenopathy | 11 (11.5) |
Pure red cell aplasia | 26 (27.1) |
Rheumatoid arthritis | 4 (4.2) |
Immune thrombocytopenia | 3 (3.1) |
Systemic lupus erythematosus | 3 (3.1) |
Sjogren's syndrome | 2 (2.1) |
Demyelinating diseases of nervous system | 2 (2.1) |
Autoimmune hemolytic anemia | 1 (1.0) |
Hypothyroidism | 1 (1.0) |
Hyperthyroidism | 1 (1.0) |
Antiphospholipid syndrome | 1 (1.0) |
Nephrotic syndrome | 1 (1.0) |
B-cell malignant lymphoma | 3 (3.1) |
Myelodysplastic syndromes | 1 (1.0) |
Megaloblastic anemia | 1 (1.0) |
Multiple myeloma | 1 (1.0) |
Positive STAT3 mutation | 7 (7.3) |
Chromosomal abnormalities | 12 (12.5) |
Seventy-nine patients and 17 patients had typical immunophenotypes and atypical immunophenotypes, respectively. These 79 cases with typical immunophenotypes were CD8+CD4-TCRαβ + . In 17 cases with atypical immunophenotypes, 8 cases were CD4+CD8-TCRαβ + and 9 cases were TCRγδ + . In TCRγδ + cases, 7 cases were both CD4 and CD8 negative while the other two cases were CD4 negative and CD8 positive.
The clinical and laboratory findings of patients T-LGLL with typical and atypical immunophenotypes were summarized in Table 2. We compared the clinical and laboratory characteristics of patients with atypical immunophenotypes and those with typical immunophenotypes. We found that presence of PRCA was more frequent in patients with typical immunophenotypes than those with atypical immunophenotypes [26/79 (32.9%) vs. 0/17 (0%), p=0.005]. In addition, compared with cases with atypical immunophenotypes, cases with typical immunophenotypes had no difference in STAT3 mutations [7/52 (13.5%) vs 0% (0/12), p=0.331]. There were no significant differences in other clinical or laboratory parameters between these two groups.
Table 2
Comparison of baseline characteristics between cases with typical and atypical immunophenotypes.
Parameters | T-LGLL with typical immunophenotype | T-LGLL with atypical immunophenotype | p |
Gender | | | 0.863 |
Male | 50.6 (40/79) | 41.2 (9/17) | |
Female | 49.4 (39/79) | 58.8 (8/17) | |
Age | | | 0.987 |
≥60 year | 43.0 (37/79) | 41.2 (8/17) | |
<60 years | 57.0 (42/79) | 58.8 (9/17) | |
Absolute lymphoctye count ≥2.5×109/L | 73.1 (52/79) | 52.9 (13/17) | 0.394 |
Absolute neutrophil count ≤1.5 × 109/L | 52.0 (41/79) | 41.2 (7/17) | 0.423 |
Hemoglobin ≤100 g/L | 58.2 (46/79) | 41.2 (7/17) | 0.200 |
Platelet count ≤100 × 109/L | 17.7 (14/79) | 11.8 (2/17) | 0.729 |
Lactate dehydrogenase ≥271 U/L | 15.2 (12/79) | 5.9 (1/17) | 0.453 |
β2-microglobulin≥2.53 mg/L | 67.1 (53/79) | 52.9 (9/17) | 0.269 |
Ferritin ≥336.2 ng/ml | 43.0 (34/79) | 23.5 (4/17) | 0.136 |
Chromosomal abnormalities | 11.4 (9/79) | 17.6 (3/17) | 0.440 |
Fatigue | 57.0 (45/79) | 47.1 (8/17) | 0.456 |
B symptoms | 17.7 (14/79) | 11.8 (2/17) | 0.729 |
Rash | 3.8 (3/79) | 5.9 (1/17) | 0.548 |
Splenomegaly | 22.8 (18/79) | 23.5 (4/17) | 1.000 |
Pure red cell aplasia | 32.9 (26/79) | 0 (0/17) | 0.005* |
Positive STAT3 mutation | 13.7 (7/52) | 0 (0/12) | 0.331 |
We then compared the clinical and laboratory features of TCRγδ + T-LGLL with TCRαβ + T-LGLL (Table 3). The frequency of PRCA was slightly lower in patients with TCRγδ + T-LGLL than in those with TCRαβ + T-LGLL [0%(0/9) vs. 30.4%(26/87),p=0.108]. The frequencies of female, STAT3 mutation, fatigue, mouth ulcer, hepatomegaly and arthralgia were lower in TCRγδ + cases than in TCRαβ + cases, although there was no statistical significance. There were no differences in other parameters between TCRγδ + cases and TCRαβ + cases. We also explored the distinction between CD4+ cases and CD4-TCRαβ + cases (Table 4). The prevalence of PRCA was slightly higher in patients with CD4+ T-LGLL than in those with CD4-TCRαβ + T-LGLL [29.9% (26/79) vs. 0% (0/8), p=0.099]. The frequencies of female, anemia, mouth ulcer and STAT3 mutation were also lower in CD4+ T-LGLL than in CD4-TCRαβ + T-LGLL, although this was not statistically significant. No differences in other clinical or laboratory features between patients with CD4+ T-LGLL and patients with CD4- T-LGLL.
Table 3
Comparison of baseline characteristics between cases with TCRγδ+ T-LGLL and TCRαβ+ T-LGLL.
Parameters | TCRγδ+ T-LGLL(%) | TCRαβ+ T-LGLL(%) | p |
Gender | | | 0.487 |
Male | 66.7(6/9) | 49.4(43/87) | |
Female | 33.3(3/9) | 50.6(44/87) | |
Age | | | 1.000 |
≥60 years | 44.4(4/9) | 42.5(41/87) | |
<60 years | 55.6(5/9) | 57.5(46/87) | |
Absolute lymphoctye count ≥2.5×109/L | 66.7(6/9) | 67.8(59/87) | 1.000 |
Absolute neutrophil count ≤1.5 × 109/L | 44.4(4/9) | 50.6(44/87) | 1.000 |
Hemoglobin ≤100 g/L | 55.6(5/9) | 55.2(48/87) | 1.000 |
Platelet count ≤100 × 109/L | 11.1(1/9) | 17.2(15/87) | 1.000 |
Lactate dehydrogenase ≥271 U/L | 11.1(1/9) | 13.8(12/87) | 1.000 |
β2-microglobulin≥2.53 mg/L | 55.6(5/9) | 65.5(57/87) | 0.716 |
Ferritin ≥336.2 ng/ml | 33.3(3/9) | 40.2(35/87) | 1.000 |
Chromosomal abnormalities | 11.1(1/9) | 12.6(11/87) | 1.000 |
Fatigue | 55.6(5/9) | 55.2(48/87) | 1.000 |
B symptoms | 11.1(1/9) | 17.2(15/87) | 1.000 |
Rash | 0(0/9) | 4.6(4/87) | 1.000 |
Splenomegaly | 22.2(2/9) | 23.0(20/87) | 1.000 |
Pure red cell aplasia | 0(0/9) | 29.9(26/87) | 0.108 |
Positive STAT3 mutation | 0(0/7) | 12.3(7/57) | 0.100 |
LGLL, large granular leukemia; TCR, T cell receptor. |
Table 4
Comparison of baseline characteristics between cases with CD4+ T-LGLL and CD4−TCRαβ+T-LGLL.
Parameters | CD4+ T-LGLL(%) | CD4−TCRαβ+T-LGLL(%) | p |
Gender | | | 0.713 |
Male | 37.5 (3/8) | 50.6 (40/79) | |
Female | 62.5 (5/8) | 49.4 (39/79) | |
Age | | | 1.000 |
≥60 years | 37.5 (4/8) | 43.0 (37/79) | |
<60 years | 62.5 (4/8) | 57.0 (42/79) | |
Absolute lymphoctye count ≥2.5×109/L | 87.5 (7/8) | 65.8 (52/79) | 0.428 |
Absolute neutrophil count ≤1.5 × 109/L | 37.5 (3/8) | 51.9 (41/79) | 0.484 |
Hemoglobin ≤100 g/L | 25.0 (2/8) | 58.2 (46/79) | 0.132 |
Platelet count ≤100 × 109/L | 12.5 (1/8) | 17.7 (14/79) | 1.000 |
Lactate dehydrogenase ≥271 U/L | 0 (0/8) | 15.2 (12/79) | 0.592 |
β2-microglobulin≥2.53 mg/L | 50.0 (4/8) | 67.1 (53/79) | 0.439 |
Ferritin ≥336.2 ng/ml | 12.5 (1/8) | 43.0 (34/79) | 0.136 |
Chromosomal abnormalities | 25.0 (2/8) | 11.4 (9/79) | 0.266 |
Fatigue | 37.5 (3/8) | 57.0 (45/79) | 0.458 |
B symptoms | 12.5 (1/8) | 17.7 (14/79) | 1.000 |
Rash | 12.5 (1/8) | 3.8 (3/79) | 0.325 |
Splenomegaly | 25.0 (2/8) | 22.8 (18/79) | 1.000 |
Pure red cell aplasia | 0 (0/8) | 32.9 (26/79) | 0.099 |
Positive STAT3 mutation | 0 (0/5) | 13.5 (7/52) | 1.000 |
LGLL, large granular leukemia; TCR, T cell receptor. |
In patients who received first-line therapy, the overall response rate (ORR) in patients with atypical immunophenotypes was higher than that in patients with typical immunophenotype (88.9%(8/9) vs. 68.4%(39/57), p=0.428), although there was no statistical significance. The ORR was 83.3% (5/6) in patients with TCRγδ + T-LGLL, compared to 70.0% (42/60) in patients with TCRαβ + T-LGLL, however, the difference was not statistically significant (p=0.664). The ORRs in CD4-TCRαβ + T-LGLL patients and CD4+ T-LGLL patients were 68.4 % (39/57) and 100% (3/3), respectively (p=0.547). The overall survival (OS) of patients with typical immunophenotype and those with atypical immunophenotype were similar (4-year OS: 87% vs. 94%, p=0.174, Figure.1A). The median survival was not reached in each group. The OS of patients with TCRγδ + T-LGLL was also similar to that of patients with TCRαβ + T-LGLL (4-year OS: 89% vs. 88%, p=0.623, Figure.1B). The survival of patients with CD4+ T-LGLL cases was not statistically different to that of CD4-TCRαβ + T-LGLL cases (4-year OS: 100% vs. 87%,p=0.173, Figure.1C).