Patients diagnosed with DLBCL and admitted to Shandong Cancer Hospital from November 2011 to December 2018 were enrolled in this retrospective study. Approval was granted by the Ethics Committee of Shandong Cancer Hospital, and all clinical records came from the electronic medical record database of Shandong Cancer Hospital.
The study criteria were as follows: 1) confirmation of DLBCL by pathological diagnosis with no prior treatment; 2) at least 6 cycles of CHOP or CDOP (liposome doxorubicin instead of epirubicin) or R-CHOP or R-CDOP regimen after diagnosis and a standard dose initial treatment regimen; 3) no bone marrow infiltration. The exclusion criteria were as follows: 1) incomplete bone marrow toxicity records; 2) lack of follow-up; 3) primary diffuse large B-cell lymphoma of the central nervous system or transformed large B-cell lymphoma of the central nervous system; 4) primary treatment in other hospitals; 5) presence of second or multiple cancers. According to the inclusion and exclusion criteria, 236 patients with DLBCL were identified and chosen for this study. The specific selection criteria are shown in Figure 1.
Treatment regimen and dose intensity
To reduce the deviation caused by the number of treatment cycles, all patients received at least 6 cycles of first-line treatment with CHOP (like) or R-CHOP (like) regimens. The initial chemotherapy doses were cyclophosphamide (750 mg/m2, Vi, d1), doxorubicin (50 mg/m2, Vi, d1-2), vincristine (1.4 mg/m2, maximum 2 mg, Vi, d1) and prednisone (100 mg, d1-5) with or without rituximab (375 mg Vi, d0). Each cycle was 21 days. Granulocyte colony-stimulating factor (G-CSF) was used when there was grade 3-4 neutropenia, but prophylactic treatment without neutropenia was prohibited.
Assessment of neutropenia
Routine blood tests were performed every 3-5 days from the first day of chemotherapy until the following cycle. In this study, CIN severity was determined by the minimum absolute neutrophil count (ANC) in the peripheral blood tested during this period. According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 4.0), CIN severity is defined as follows: Grade 1, ANC 1.5-2.0 x 109 / L; Grade 2, ANC 1.0-1.5 x 109 / L; Grade 3, ANC 0.5-1.0 x 109 / L; and Grade 4, ANC 0-0.5 x 109 / L. Absence of CIN is defined as ANC > 2.0 x 109 / L. Grade 1 and Grade 2 neutropenia are considered mild neutropenia, and Grade 3 and Grade 4 neutropenia are considered severe neutropenia. According to the CIN occurrence times, CIN occurring during the third cycle of treatment was regarded as the bound, early-onset was CIN occurring during weeks 1-3, late-onset was CIN occurring during the fourth cycle or later, and absence of CIN was no CIN occurrence during the entire treatment. Among them, the late-onset group and CIN-absent group were collectively referred to as the non-early-onset group.
Efficacy and survival assessment
Efficacy was evaluated according to imaging remission (CT/MRI) or metabolic remission (PET/CT) as per the revised 2014 Lugano criteria. Efficacy was evaluated every two cycles after treatment and divided into complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD). The objective response rate (ORR) was the proportion of patients with CR and PR.
The follow-up end points were OS and PFS, and the follow-up deadline was January 30, 2021. OS is defined as the duration from the beginning of treatment to date of death for any cause. PFS is defined as the duration from the beginning of treatment to time of tumor progression or death of any cause.
IBM SPSS Statistics software (version 22.0) and GraphPad Prism software (version 5.0) were used for the statistical analysis and to generate the graphs. Descriptive statistics was used to describe the baseline characteristics of patients, and a chi-square test was used to compare the baseline characteristics. The Kaplan-Meier method (logarithmic rank test) was used to construct the survival curve. Prognostic factors of OS and PFS were determined through univariate and multivariate Cox regression (enter method) analyses. Variables with P<0.1 from the univariate analysis were entered into multivariate analysis. P < 0.05 was defined as a statistically significant difference.