Prognostic significance of PCR-based molecular staging in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy

Abstract

The prognostic role of detecting clonal immunoglobulin gene rearrangement (IgR) from bone marrow (BM) aspirates was evaluated by BIOMED-2 PCR in 97 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP immunochemotherapy. Sixteen (16.5%) patients had BM involvement (BMI) defined by BM biopsy (MOR+) and 39 (40.2%) had positive IgR (PCR+). Patients with MOR + BMI showed inferior event-free survival (EFS) compared to those with MOR-/PCR- (p < 0.001) or those with MOR-/PCR + BMI (p = 0.002), while no significant difference in EFS was observed between patients with MOR-/PCR + and those with MOR-/PCR - BMI (p = 0.497). Use of the BIOMED-2 for PCR resulted in significant increase in detection of BMI. However, the increased sensitivity by PCR did not translate into improved prediction of prognosis, emphasizing the essential role of histopathological review of trephine biopsy for the detection of BMI.

Monoclonal gammopathies regardless of subtypes are associated with poor prognosis of diffuse large B-cell lymphoma

“…[ 3 ] However, the International Prognostic Index (IPI), which was developed in the era of chemotherapy treatment for aggressive lymphoma, has proven to be less powerful in the rituximab era. To better distinguish tumor prognosis, several models [ 4 , 5 ] and algorithms [ 6 , 7 ] have been developed. In addition, several markers have been discovered in DLBCL, to better identify patients who will likely have a poor therapeutic response.…”

Diagnostic accuracy and prognostic relevance of immunoglobulin heavy chain rearrangement and 18 F-FDG- PET/CT compared with unilateral bone marrow trephination for detecting bone marrow involvement in patients with diffuse large B-cell lymphoma

“…If the additional less invasive tools for determining BMI can use for detecting focal or diffuse BM involvement, it will be helpful to diagnosis or prognosis in patients with DLBCL. Many approaches have been used for determining BMI, such as PCR ampli cation of immunoglobulin gene rearrangement or FDG/PET-CT [7,19,20,[24][25][26]. To our knowledge, this was the rst trial to evaluate the prognostic value of a combination of FDG PET/CT and PCR-based clonality for the treatment of DLBCL.…”

B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy

“…Resistance in lymphoid cells for ABT-199 has been documented [ 189 ]. Some diseases are liable to be as dependent on one Bcl-2 protein as CLL; the majority of tumors will likely require combinations of these drugs to have a significant therapeutic impact; however, these combinations may show unacceptable toxicity [ 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 ].…”

“…Bcl-2 is a 26 kDa, 239 amino-acid protein that composes four domains, BH1, BH2, BH3, and BH4 [38,76]. The BH4 domain residues (10-30), BH3 domain residues (93-107), BH1 domain residues (136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151)(152)(153)(154)(155), and BH2 domain residues (187)(188)(189)(190)(191)(192)(193)(194)(195)(196)(197)(198)(199)(200)(201)(202) [76] (https://www.uniprot.org/uniprot/P10415#structure; accessed on 15 August 2021) (Figure 3A) and the amino acid sequences of the BH1-4 domains of Bcl-2 [76] (Figure 3B) are provided. The structure of a Bcl-2 chimeric protein comprising a truncated loop obtained from Bcl-xL among the Hα1 as well as Hα2 was initially observed through NMR spectroscopy [77].…”