Patient characteristics

A total of 199 patients were identified (Table 1), with a median age of 70 years (range 28–87). 81% were > 60 years, 51% were male, 68% were Stage III/IV, 60% had IPI score 3–5, and 16% were diagnosed in other facilities. Forty-eight percent were treated with CHOP, 52% were given dose-reduced THP-COP regimen, and 94% were combined with rituximab. The reasons for omitting Rituximab were CD20 negativity (n = 1), severe infusion reaction (n = 1), early death before using Rituximab (n = 2), concerns about tumor lysis syndrome (n = 4), and details unknown (n = 4).

Table 1 Patient clinical and laboratory characteristics.

A median DTI was 22 days (range 0–393) (Fig. 1). Seventy-five percent of patients received treatment within 36 days from pathological diagnosis and 97% within 100 days. Six patients received treatment 100 days after diagnosis. Although the cause of treatment delay was not fully recorded, the reason of the delay for these six patients seems to due to comorbidities (n = 5) and poor economy (n = 1). When we divided patients into two groups by DTI, short DTI (0–22 days) was associated with clinical factors such as older age, poorer PS, B symptoms, lower serum albumin, elevated LDH, higher Ann Arbor stage, and higher IPI. Sex, extranodal lesions, bulky lesion, facility of initial diagnosis, and treatment regimen were not associated with DTI.

Figure 1
figure1

Distributions of diagnosis-to-treatment interval.

Overall and progression-free survival

With a median follow-up of 1091 days (range 31–3951), 69 patients had died and 88 patients had PFS events (75 progression and 13 death without progression). The 2-year OS and PFS were 74.6% and 65.4%, respectively. The median survival was not reached. The median PFS was 91 months.

At 2 years, patients with short DTI (0–22 days) showed significantly poorer OS (62.7% vs 86.4%; p < 0.001, Fig. 2a) and PFS (55.1% vs 75.9%; p < 0.001, Fig. 2b) compared to those with long DTI (over 22 days). When we divided patients into quartile by DTI, shorter DTI (0–10 days,11–22 days) remained to be associated with significantly poorer OS compared to longer DTI (23–36 days, over 36 days, Fig. 2c). Patients with DTI of 23–36 days tend to show better OS compared to those with DTI of over 36 days (p = 0.108). We observed a nonlinear association with 2-year OS and DTI (Fig. 2d). The 2-year OS was lowest for patients with DTI of 5–15 days, highest for those with DTI of 30–40 days, and decreased afterward.

Figure 2
figure2

Survival of patients. Kaplan–Meier curves of overall survival (OS) (a) and progression-free survival (b) by diagnosis-to-treatment interval (DTI) divided into two groups. (c) Kaplan–Meier curves of OS by DTI divided into quartile. *p < 0.001; #p < 0.05. (d) Two-year OS according to DTI. Nonlinear relationship was modeled using polynomial regression.

Univariate and multivariate analysis

Univariate analysis showed that the parameters negatively affecting OS and PFS were as follows: short DTI (0–22 days), poorer PS, B symptoms, lower serum albumin, elevated LDH, higher Ann Arbor stage, extranodal lesions, higher IPI score, and nonuse of rituximab (Table 2). Older age and dose-reduced THP-COP regimen negatively affected OS alone.

Table 2 Factors associated with survival by univariate analysis.

Short DTI (0–22 days), B symptoms, lower serum albumin, higher IPI score, nonuse of rituximab, and dose-reduced THP-COP regimen were evaluated with multivariate analysis for OS. Short DTI (0–22 days) (HR 2.03, 95% CI [1.18, 3.52], p = 0.011), nonuse of rituximab (HR 2.88, 95% CI [1.39, 5.96], p = 0.005), and IPI score (HR 1.25, 95% CI [1.001, 1.55], p = 0.049) were revealed as independent factors affecting OS (Table 3). Short DTI (0–22 days), B symptoms, lower serum albumin, higher IPI score, and nonuse of rituximab were evaluated with multivariate analysis for PFS. Similar as for OS, short DTI (0–22 days) (HR 2.08, 95% CI [1.31, 3.33], p < 0.001), nonuse of rituximab (HR 3.68, 95% CI [1.67, 8.09], p = 0.001), and IPI score (HR 1.45, 95% CI [1.22, 1.72], p = 0.002) were revealed as independent factors affecting PFS (Table 3). With a multivariate analysis including the additional factors such as age, Ann Arbor stage, extranodal lesions, elevated LDH, and poorer PS, the significance of short DTI (0–22 days) and nonuse of rituximab for OS and PFS remained.

Table 3 Factors associated with survival by multivariate analysis.