Plasma Cell Myeloma with IGHV Deletion: A Subset of Patients with Poor Prognosis.
Gary Lu, Shaoying Li, Faisal Alseraye, Ramya Muddasani, Lynne Abruzzo, Michael Wang, James M You, L Jeffrey Medeiros. UT MD Anderson Cancer Center, Houston, TX
Background: IGH rearrangement is one of the most common cytogenetic abnormalities in plasma cell myeloma (PCM). A number of different partner genes are involved in IGH rearrangements. With the exception of IGH/CCND1, IGH gene translocations/rearrangements identified have been associated with high risk disease. The goal of this study is to elucidate the clinical significance of deletions of the variable segments of the IGH gene (IGHV) in PCM.
Design: We collected PCM cases with del(IGHV) detected by fluorescence in situ hybridization (FISH) from the cytogenetics database over 2 years from 02/2008 to 02/2010. FISH probes used included IGH breakapart, del(13q)/Rb1, del(17p)/TP53, IGH/FGFR3, IGH/MAF, c-MYC, and IGH/CCND1. Results of conventional cytogenetic analysis were also reviewed. Clinicopathologic data were systemically collected from the medical records.
Results: The study cohort consisted of 17 cases of PCM with del(IGHV). The estimated frequency of this abnormality is 5%. There were 12 men and 5 women with a median age of 64 years (range, 49 – 79 years). Clinical features included an elevated serum β2M in all 16 cases assessed, and bone lesion and/or renal failure in 14/17 (82%) patients. Morphologically the plasma cells were further classified as low-grade/mature in 3/17 (18%), intermediate-grade in 8/17 (47%), and high-grade/highly atypical in 6/17 (35%). Plasma cell clonality was confirmed in all the 17 cases, with 13 (76%) cases CD56+ and 3 (18%) cases CD20+. At the molecular level, these cases can be divided into four subgroups: (1) isolated del(IGHV) (4/17; 24%); (2) del(IGHV) and IGH/CCND1 without other abnormalities (3/17; 18%); (3) del(IGHV) and c-MYC rearrangement (4/17; 24%); and (4) del(IGHV) and IGH breakapart with other markers (6/17; 35%). Group 4 included del(13q)/Rb1 and del(17p)/TP53 (n=3), IGH/FGFR3 (n=1), del(13q)/Rb1 (n=1), and del(17p)/TP53 (n=1). A chromosomal abnormality involving 14q32 was detected by routine cytogenetics in 5 cases including 2 with a t(8;14)(q24.1;q32). Patients received high-dose chemotherapy (16/16 available) with a partial to poor response to therapy in 15 patients (94%). Del(IGHV) was detected at time of presentation, prior to any therapy, in 8 patients.
Conclusions: Del(IGHV) occurs in 5% or less of cases of PCM. The clinicopatholoic findings of this cohort suggest that del(IGHV) is a marker of poor prognosis. Routine assessment of PCM cases for del(IGHV), conveniently assessed by FISH, is appropriate in cytogenetic workup of PCM patients.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 243, Tuesday Morning