18-FDG PET-CT Scan Is a Good Tool to Detect Bone Marrow Involvement in Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Analysis of 602 Patients

Background:

Bone marrow biopsy is considered a gold standard to detect the involvement in lymphomas. Multi-color flow cytometry improves the detection of low-volume disease and is expected to increase the sensitivity over a BM Biopsy. These procedures are painful, expensive and with the widespread use of ¹⁸FDG PET-CT scan as the preferred staging scan, their utility is being re-evaluated. We analyzed the utility of BM studies, including multi-color flow cytometry in DLBCL and developed an algorithm to identify patients where it would be useful.

Methods:

This is a retrospective study from a tertiary care center in India conducted on patients registered from 01/2018 till 12/2019. De-novo patients aged ≥15 years with DLBCL who underwent their staging workup including both a PET-CT scan and BM studies were included for this analysis. Bone marrow studies include assessment by morphology, flow cytometry (optional) and biopsy. A 13-16 color multi-parameter flow cytometry (BD Fortessa) was used and 500,000 to 1 million events were acquired for the analysis. We recorded the baseline characteristics, Lugano staging and findings from the PET-CT scan and Bone marrow studies. The primary objective was to study the value of BM studies in altering the stage and management compared to a PET-CT scan. Additionally, the positive and negative predictive value of PET-CT scan, reasons for discordant findings, value of flow cytometry studies and impact of BM studies on the final prognostic index were analyzed.

Results:

A total of 698 DLBCL patients were registered during the period, 602(86%) of whom underwent both a PET-CT scan and Bone marrow studies. Flow cytometry was performed in 572 patients (95%). The median age was 52 years (15-82 years), 425 (70%) were male patients. The stage-wise distribution was; stage I-64(11%), stage II-118(20%), stage III- 74(12%) and stage IV- 346(57%) patients. The utility of PET-CT scan and BM studies in classifying a patient as stage IV is summarized in Table 1. BM studies upstaged a patient to stage IV in only 18 (3%) cases. In the absence of BM studies, these patients would be classified as stage I (4), stage II (4) and stage III (10) (Table 2). A change in prognosis would happen in only 4 of these patients due to a change in stage in 3 (stage I-1, stage II-2) and a change in NCCN-IPI from low-intermediate to high-intermediate in one patient. A change in treatment would occur in only 1 patient. The PPV and NPV of PET-CT for BM involvement using BM studies as a gold standard were 44.2% and 92.3% respectively. While 23/29 (79%) diffuse uptake on PET scan was detected by BM studies, only 35/102 (34%) focal uptake was detected by BM studies. The histological involvement was concordant in 63 patients, while 32 patients had a discordant histological finding. Flow cytometry alone was positive in 32(5.6%) patients, of which 27 patients were already classified as advanced stage (Stage III-7, Stage IV-20).

Conclusions:

Bone marrow studies, including flow cytometry can be avoided in patients with DLBCL who undergo a PET-CT scan. The additional value of BM studies from a prognostic or therapeutic view is too low to justify a regular use of this painful and expensive test.