Prognostic Significance of Bone Marrow Infiltration Detected By PET-CT in Newly Diagnosed Diffuse Large B Cell Lymphoma
Authors: Liang Jin-Hua , Sun Jin , Wang Li , Fan Lei , Tian-Nv Li , Li Jian-Yong , Xu Wei 
Published: October 2019

Abstract
Purpose
The aim of this study was to examine the prognostic value of bone marrow involvement (BMI) assessed by PET-CT in treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL).
Patients and methods
All patients from a single centre diagnosed as DLBCL between 2005 and 2014 had data extracted from staging PET-CT, bone marrow biopsy (BMB), and treatment records. The final diagnosis of BMI was defined as: (i) positive bone marrow biopsy; (ii) positive PET-BMI confirmed by guided biopsy or targeted MR imaging; (iii) concomitant disappearance of bone marrow uptake and uptake in other lymphoma lesions on PET-CT after R-chemotherapy.
Results
Of 169 patients, 20 patients (12%) had BMI on BMB, whereas 35 patients (21%) had positive BMI according to PET-CT findings (PET-BMI(+)). Thirty-three out of the 35 patients with PET-BMI(+) showed a focal pattern and 2 a diffuse pattern, respectively. In multivariate analyses, PET-BMI(+) remained significant for overall survival (OS) (HR 2.90, 95%CI 1.21−6.96, P=0.017) while progressive-free survival (PFS) was significant only in univariate analysis (P<0.001) (Table 1). Among patients with PET-BMI(+) at diagnosis (N=35), patients with SUVmax of bone marrow (SUVmax(BM)) more than 8.6 were significantly associated with high IPI score (3−5) (P=0.002) and worse PFS and OS (P=0.025 and P=0.002, respectively) (Figure 1). In the 68 stage IV cases, three-year OS was higher for patients with negative PET-BMI (PET-BMI (−)) than patients with PET-BMI(+) (84.2%¡À6.5% vs. 44.1%¡À8.6%, respectively; P=0.003) while PFS only shown a trend of statistic significance (P=0.077) between the 2 groups, with estimates of 3-year PFS at 49.3%¡À9.2% and 28.6%¡À7.6%, respectively (Figure 2). Among the 69 patients with inter-risk of IPI (2−3), patients with PET-BMI(+) (N=21) had significantly inferior PFS and OS than patients with PET-BMI(−) (N=48) (P =0.009 and P<0.001, respectively) (Figure 3).
Conclusions
Our data raised several important issues about the predictive significance of BMI assessed by PET-CT in DLBCL: (i) The bone marrow status assessed by PET-CT is an independent predictor of OS independent of IPI; (ii) For baseline PET-BMI(+) patients, the optimal cutoff value of SUVmax(BM) to predict the survival outcomes was 8.6; (iii) In patients with stage IV disease, worse survival outcomes were observed in patients with BMI than that without BMI; (iV) Patients with PET-BMI(+) in the intermediate risk-group should be managed as high-risk group patients.
Table 1. Cox regression analysis for PFS and OS for all the patients with DLBCL (N=169) PFS OS Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis HR (95%CI) P HR (95%CI) P HR (95%CI) P HR (95%CI) P PET-BMI+ 3.96 (2.38-6.59) <0.001 - - 6.73 (3.40-13.34) <0.001 2.90 (1.21-6.96) 0.017 BMB-BMI+ 4.49 (2.53-7.98) <0.001 - - 6.24 (3.06-12.73) <0.001 - - IPI>2 7.27 (4.19-12.63) <0.001 3.12 (1.31-7.47) 0.010 9.02 (3.94-20.61) <0.001 3.62 (1.01-13.03) 0.049 Age >60 1.61 (0.98-2.64) 0.060 1.18 (0.61-2.27) 0.627 Stage III or IV 6.08 (2.77-13.36) <0.001 - - 6.78 (2.08-22.12) 0.002 - - ECOG 2-4 2.79 (1.65-4.71) <0.001 1.97 (1.12-3.47) 0.019 3.39 (1.75-6.55) <0.001 - - LDH>ULN 4.68 (2.82-7.78) <0.001 - - 4.31 (1.96-9.48) <0.001 - - Extranodal site >1 3.15 (1.91-5.18) <0.001 - - 3.04 (1.58-5.86) 0.001 - -
Figure 1. Survivals according to SUVmax in patients with PET-BMI(+) at diagnosis Figure 1. Survivals according to SUVmax in patients with PET-BMI(+) at diagnosis Figure 2. Survivals according to PET-BMI status in cases with stage IV Figure 2. Survivals according to PET-BMI status in cases with stage IV Figure 3. Survivals according to PET-BMI status in cases with IPI score of 2-3 Figure 3. Survivals according to PET-BMI status in cases with IPI score of 2-3

Disclosures
No relevant conflicts of interest to declare.