A simplified prognostic score for T-cell large granular lymphocyte leukaemia

Figures & data

Table 1. Patients’ baseline characteristics of the included patients

Characteristics	N = 120
Age of diagnosis, year, median (IQR)	59 (49, 66)
Age of diagnosis >60 year, n (%)	52 (43.3)
Male sex, n (%)	62 (51.7)
Symptoms and signs
Asymptomatic, n (%)	28 (23.3)
Fatigue, n (%)	69 (57.5)
Recurrent infections, n (%)	22 (18.3)
Autoimmune phenomenon, n (%)	48 (40)
B symptoms, n (%)	24 (20)
Hepatomegaly, n (%)	4 (3.3)
Splenomegaly, n (%)	24 (20)
Lymphadenopathy, n (%)	18 (15)
ECOG PS >2, n (%)	13 (10.8)
Laboratory tests
LGL, × 10^9/L, median (IQR)	2.91 (1.11, 4.42)
LGL <1 × 10^9/L, n (%)	23 (19.2)
ALC, × 10^9/L, median (IQR)	3.6 (2.06, 6.52)
ALC >4 × 10^9/L, n (%)	55 (45.8)
ANC, × 10^9/L, median (IQR)	1.40 (0.89, 2.46)
ANC <1 × 10^9/L, n (%)	36 (30)
ANC <0.5 × 10^9/L, n (%)	14 (11.6)
Hemoglobin, g/L, median (IQR)	84.5 (64, 114.5)
Hemoglobin <110 g/L, n (%)	84 (70)
Platelets, × 10^9/L, median (IQR)	179.5 (130.75, 232.25)
Platelets <100 × 10^9/L, n (%)	22 (18.3)
LDH, U/L, median (IQR)	202 (176, 242)
LDH > UNL, n (%)	19 (15.8)
Positive STAT3 mutations, n (%)	14 (17.5)
Comorbidity
Pure red-cell anemia, n (%)	30 (25)
Rheumatoid arthritis, n (%)	6 (5)
aCCI score >2, n (%)	32 (26.7)

Missing data: STAT3 mutations (n = 40)

IQR: interquartile range; ECOG PS: Eastern Cooperative Oncology Group performance status; LGL: large granular lymphocyte; ALC: absolute lymphocyte count; ANC: absolute neutrophil count; LDH: lactate dehydrogenase; UNL: upper normal limit; aCCI: age-adjusted Charlson Comorbidity Index.

Figure 1. Overall survival curve for the entire study population.

Figure 2. Construction and validation process of a decision tree model for predicting the overall survival of patients with T-cell large granular lymphocyte leukaemia. (A–B) Feature selection steps carried out using the lasso regression model; (C) Univariate and multivariate Cox regression analyses; (D) A simplified decision-tree model; (E) Kaplan-Meier survival curves of the three risk groups; (F) Time-dependent receiver operating characteristic curves displaying predictive accuracy for various timeframes (2-, 5-, and 10-year overall survival); (G) Calibration curves for the same three survival periods; and (H) A comparison of time-dependent AUC between the decision tree model and the nomogram model. HR: hazard ratio; CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; aCCI: age-adjusted Charlson Comorbidity Index; LGL: large granular lymphocyte; Int: intermediate; TPR: true positive rate; FPR: false positive rate; AUC: area under the curve.

Figure 3. Correlation analysis of the correlation with performance status. ECOG PS: Eastern Cooperative Oncology Group performance status; aCCI: age-adjusted Charlson Comorbidity Index.

Table 2. Comparisons of baseline characteristics between different risk subgroups

Characteristics	Low risk	Int risk	High risk	Pint/low	Phigh/low	Phigh/int
	n = 89	n = 18	n = 13
Age of diagnosis, year, median (IQR)	59 (49–64)	56 (49–67)	65 (61–77)	0.825	0.062	0.147
Male sex, n (%)	44 (49.4)	10 (55.6)	8 (61.5)	0.636	0.415	1.000
Symptomatic, n (%)	62 (69.7)	17 (94.4)	13 (100)	0.059	0.048	1.000
Fatigue, n (%)	45 (50.6)	11 (61.1)	13 (100)	0.414	0.001	0.025
Recurrent infections, n (%)	12 (13.5)	7 (38.9)	3 (23.1)	0.025	0.622	0.452
Autoimmune phenomenon, n (%)	28 (31.5)	10 (55.6)	10 (76.9)	0.051	0.004	0.275
B symptoms, n (%)	11 (12.4)	8 (44.4)	5 (38.5)	0.004	0.045	1.000
Hepatomegaly, n (%)	2 (2.2)	1 (5.6)	1 (7.7)	1.000	0.836	1.000
Splenomegaly, n (%)	14 (15.7)	7 (38.9)	3 (23.1)	0.054	0.791	0.452
Lymphadenopathy, n (%)	10 (11.2)	7 (38.9)	1 (7.7)	0.010	1.000	0.095
ECOG PS >2, n (%)	0 (0)	0 (0)	13 (100)	–	<0.001	<0.001
LGL, × 10^9/L, median (IQR)	2.97 (1.16, 4.54)	1.81 (1.01, 4.09)	2.91 (0.73, 4.13)	0.363	0.416	0.837
ALC, × 10^9/L, median (IQR)	3.9 (2.25, 6.98)	2.75 (1.89, 5.85)	2.1 (1.07, 5.18)	0.224	0.138	0.465
ANC, × 10^9/L, median (IQR)	1.38 (0.83, 2.26)	1.5 (0.52, 2.55)	1.41 (1.05, 2.64)	0.774	0.446	0.496
Hemoglobin, g/L, median (IQR)	85 (64, 123)	95.5 (68.25, 111.75)	75 (61, 88)	0.864	0.049	0.033
Platelets, × 10^9/L, median (IQR)	199 (162, 236)	68 (34.25, 76.75)	168 (55, 282)	<0.001	0.388	0.003
LDH, U/L, median (IQR)	195.5 (169, 231.25)	239.5 (199.25, 297.75)	236 (215.75, 302.5)	0.023	0.005	0.882
Positive STAT3 mutation, n (%)	11 (17.2)	3 (30)	0 (0)	0.598	0.580	0.250
Pure red-cell anemia, n (%)	21 (23.6)	2 (11.1)	7 (53.8)	0.389	0.051	0.017
Rheumatoid arthritis, n (%)	4 (4.5)	1 (5.6)	1 (7.7)	1.000	1.000	1.000
aCCI score > 2, n (%)	18 (20.2)	4 (22.2)	10 (76.9)	1.000	<0.001	0.004

Missing data: STAT3 mutations (n = 40).

Int: intermediate; IQR: interquartile range; ECOG PS: Eastern Cooperative Oncology Group performance status; LGL: large granular lymphocyte; ALC: absolute lymphocyte count; ANC: absolute neutrophil count; LDH: lactate dehydrogenase; aCCI: age-adjusted Charlson Comorbidity Index.

Statistically significant p-values are written in bold.

Figure 4. Sankey plot Illustrating relationship and distribution between risk stratification and treatment. Int: intermediate; MTX: methotrexate; CTX: cyclophosphamide; CsA: cyclosporine; CR: complete remission; PR: partial remission.

Figure 5. Treatment outcomes of different risk groups for first-line therapies. Note: Data for cyclophosphamide is not shown due to the limited number of cases. The other treatment regimens used were CHOP (cyclophosphamide + doxorubicin + vincristine + prednisone), EPOCH (etoposide + doxorubicin + cyclophosphamide + vincristine + prednisone), FC (fludarabine + cyclophosphamide), and so on. ORR: overall response rate; CI: confidence interval; CRR: complete remission rate; Int: intermediate; MTX: methotrexate; CsA: cyclosporine.

Data availability statement

The data generated in this study are available upon request from the corresponding author.