Role of FDG-PET/CT for Detection of Occult Bone Marrow Involvement in Patients from the Middle East and North Africa Region with Hodgkin Lymphoma
Authors: Damlaj Moussab , Gmati Giamal Edin Mohamed , Syed Ghulam , Al Zahrani Mohsen , Abuelgasim Khadega Ahmed , Rather Mushtaq , Hend Salama , Ayman Hejazi , Jazieh Abdul-Rahman , Askar Ahmed 
Published: October 2019

Abstract
Background: Routine bone marrow biopsy (BMB) for the initial staging of Hodgkin Lymphoma (HL) is not recommended in the era of FDG-PET/CT staging (J Clin Oncol. 2014;32(27):3059). However, patients from the Middle East and North Africa (MENA) region have epidemiologic and clinical features of lymphoma that are different from patients of other ethnicities (J Natl Compr Canc Net2010;8:S-29-S-35). Therefore, it is unknown whetherFDG-PET/CT can substitute for staging BMB in this population.At our center, we perform routine BMB for all newly diagnosed lymphoma cases.
Aim: To investigate whether routine BMB is essential in detecting bone marrow disease where FDG-PET/CT is used in initial staging for HL in patients from the MENA region.
Methods: Patients with HL at our institution between 2010 - 2015 were identified. Inclusion criteria included newly diagnosed patients who had BMB and FDG-PET/CT as part of initial staging. All baseline and laboratory features were retrospectively extracted. Pathology reports of bone marrow aspirate and trephine biopsies were reviewed by two independent Hematologists. All written FDG-PET/CT reports were retrieved and carefully reviewed and cases with positive skeletal uptake were re-interpreted by an experienced radiologist. Pattern of skeletal FDG-PET/CT uptake was determined and classified as unifocal or multifocal. Sensitivity and specificity was computed while defining bone marrow disease by positive BMB and / or focal skeletal uptake on FDG-PET/CT. Categorical and continuous variables were analyzed using Pearson's chi-squared and Student's t-test, respectively.
Results:
A. Baseline characteristics:
A total of92 patients met the inclusion criteria and were considered for this analysis. All patients were from the MENA region and > 90% were from the Arabian peninsula. From this cohort, bone marrow disease was detected in 7 (7.6%) patients using BMB while 20 (21.7%) patients had unifocal or multifocal bone marrow uptake on FDG-PET/CT. An additional 21 patients (23%) had diffuse homogenous FDG uptake and was not considered to represent HL. The cohort was characterized by a male to female ratio of 1.4 and a median age at diagnosis of 27 years (6-83). About two thirds of the cases were classical HL of the nodular sclerosis subtype (Table 1). Almost 60% of cases were stage III - IV with corresponding median IPS of 2 (0-6). Incidence of bulky disease and B-symptoms among the entire cohort was 32% and 50%, respectively.
B. Comparison of FDG-PET/CT and BMB
No patient with involved BMB (iBMB) had early stage disease on FDG-PET/CT and BMB identified only one patient with positive BM involvement yet negative skeletal uptake on FED-PET/CT. Involvement by BMB upstaged 3 patients previously assessed by CT scan as having stage III, however, none of the patients were allocated to a different treatment plan based on the BMB result. On the other hand, FDG-PET/CT upstaged 24 patients (26%); 9 patients from stage III to IV and 14 patients from early to advanced stage resulting in change of therapeutic plan in the latter group. Focal skeletal FDG-PET/CT lesions identified positive marrow disease with a sensitivity and specificity of 95.2% and 70.4%, respectively. On the other hand, sensitivity and specificity of BMB was 35% and 100%, respectively (Table 2).
Abnormal skeletal FDG uptake was seen in a total of 20 patients (21.7%); 11 (55%) had unifocal / bifocal while 9 (45%) had multifocal disease of the axial skeleton. Patients with iBMB compared to those with negative BMB but positive unifocal / multifocal skeletal FDG-PET/CT lesions were more likely to be male (p = 0.002), have B-symptoms (p = 0.028), extranodal disease (p = 0.017) and more likely to have multifocal uptake on FDG-PET/CT (0.017) (Table 3).
Conclusion:To our knowledge, this is the first analysis to examine the role of FDG-PET/CT for detection of bone marrow involvement in HL in a patient cohort from the MENA region. We observed that FDG-PET/CT had a higher sensitivity and negative predictive value compared to BMB leading to a treatment change in a significant proportion of patients. This analysis highlightsthat FDG-PET/CT can substitute for BMB in routine staging for newly diagnosed patients with HL from the MENA region.

Disclosures
No relevant conflicts of interest to declare.