J Korean Med Sci.  2022 Jan;37(1):e2. 10.3346/jkms.2022.37.e2.

Diagnostic Accuracy and Prognostic Relevance of Immunoglobulin Heavy Chain Rearrangement and 18F-FDGPET/CT Compared With Unilateral Bone Marrow Trephination for Detecting Bone Marrow Involvement in Patients With Diffuse Large B-Cell Lymphoma

• Kim M
• Ahn SY
• Ahn JS
• Song GY
• Jung SH
• Lee JJ
• Kim HJ
• Lee JH
• Shin MG
• Song SY
• Yang DH

• KMID: 2524180
• DOI: http://doi.org/10.3346/jkms.2022.37.e2

Abstract

Background
In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction.
Methods
A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis.
Results
A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively).
Conclusion
This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

Keyword

Immunoglobulin Heavy Chain; PET/CT; Bone Marrow Involvement; Diffuse Large B Cell Lymphoma

Figure

• 

  Fig. 1 Case example of PET/CT images showing FDG BM uptake in DLBCL patients. (A) Coronal images show focal increased marrow FDG uptake with iliac crest. (B) Coronal and sagittal image show focal increased FDG BM uptake in T6-T7 vertebrae without iliac crest. (C) Coronal and sagittal images show diffuse increased FDG BM uptake.FDG = fluorodeoxyglucose F 18, PET/CT = positron emission tomography-computed tomography, DLBCL = diffuse large B-cell lymphoma.

• 

  Fig. 2 Kaplan-Meier survival curves of patients with diffuse large B-cell lymphoma according to the bone marrow involvement status assessed by (A) BM biopsy; (B) combined assessment with polymerase chain reaction-based clonality and morphology; (C) combined assessment with PET/CT and morphology. Survival panels present the 3-year PFS curves (left) and 3-year OS curves (right). Statistical differences were calculated using the Breslow test and log rank test.PFS = progression-free survival, mBMI = morphologic bone marrow involvement, IgH BMI = immunoglobulin heavy chain rearrangement bone marrow involvement, OS = overall survival, PET BMI = positron emission tomography-computed tomography bone marrow involvement.

• 

  Fig. 3 Kaplan-Meier survival curves of patients with diffuse large B-cell lymphoma according to the bone marrow involvement status assessed by (A) combined PET/CT and PCR-based clonality; (B) combined assessment with PET/CT, PCR-based clonality and morphology. Survival panels present the 3-year PFS curves (left) and 3-year OS curves (right). Statistical differences were calculated using the Breslow test and log rank test.PFS = progression-free survival, PET BMI = positron emission tomography-computed tomography bone marrow involvement, IgH BMI = immunoglobulin heavy chain rearrangement bone marrow involvement, OS = overall survival, mBMI = morphologic bone marrow involvement, PET/CT = positron emission tomography-computed tomography, PCR = polymerase chain reaction.

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