Prognostic Significance of Bone Marrow Infiltration Detected By PET-CT in Newly Diagnosed Diffuse Large B Cell Lymphoma

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 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

Disclosures: No relevant conflicts of interest to declare.

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