Introduction Canine diffuse large B-cell lymphoma (cDLBCL) accounts for 30-40% of lymphoma cases. The persistence of cells unidentifiable through cytology is termed Minimal Residual Disease (MRD). Currently, MRD is measured by flow-cytometry (FC). The aim of the study was to determine the diagnostic and prognostic role of rearranged IgH (PARR analysis) in the lymph node (LN), peripheral blood (PB) and bone marrow (BM) in cDLBCL compared with FC. Materials and methods PB, BM aspirate and LN tissue from 17 DLBCL were available for PARR analysis at diagnosis (T0) and at the end of treatment (T1). The concordance between PARR and FC was analyzed for LN, PB and BM. Results At T0, the B-cell origin of the lymphomas was confirmed by IgH Major rearrangements in the LN of all dogs. Eleven dogs (64.7%) showed simultaneous IgH rearrangements in BM and PB, whereas 6 dogs (35.3%) had no rearrangements in none of the samples. At T1, IgH monoclonal rearrangement was found in 13 (81%), 8 (50%) and 6 dogs (38%) in LN, PB and BM, respectively. At T0, the concordance rate between FC and PARR was 100%, 82% and 47% for LN, PB and BM, respectively. The highest concordance rate was obtained in LNs (PARR-positive/FC-positive), whereas the highest discordance was obtained in BM (PARR-positive/FC-negative). At T1, the concordance rate was overall reduced, accounting for 47%, 50%, and 63% in LN, PB and BM, respectively. The highest discordance rate was found in LNs (PARR-positive/FC-negative), whereas the highest concordance was found in BM (PARR-negative/FC-negative). Discussion We propose the use of both, PARR and FC, in tandem to offset the possibility of false-negative MRD assessment; in case of discrepant results, dogs should be closely monitored to detect a possible early recurrence. The concordance rate was largely dependent on the time point, being higher in T0. The discordance between PARR and FC results in dogs in clinical remission may be due to the limited number of available cells, which reduces the sensitivity of FC.
Minimal Residual Disease assessment based on IgH rearrangements and flow cytometry in canine Diffuse Large B-cell Lymphoma
ARICO', ARIANNA;FERRARESSO, SERENA;GIANTIN, MERY;DACASTO, MAURO;GUADAGNIN, ELEONORA;ARESU, LUCA
2013
Abstract
Introduction Canine diffuse large B-cell lymphoma (cDLBCL) accounts for 30-40% of lymphoma cases. The persistence of cells unidentifiable through cytology is termed Minimal Residual Disease (MRD). Currently, MRD is measured by flow-cytometry (FC). The aim of the study was to determine the diagnostic and prognostic role of rearranged IgH (PARR analysis) in the lymph node (LN), peripheral blood (PB) and bone marrow (BM) in cDLBCL compared with FC. Materials and methods PB, BM aspirate and LN tissue from 17 DLBCL were available for PARR analysis at diagnosis (T0) and at the end of treatment (T1). The concordance between PARR and FC was analyzed for LN, PB and BM. Results At T0, the B-cell origin of the lymphomas was confirmed by IgH Major rearrangements in the LN of all dogs. Eleven dogs (64.7%) showed simultaneous IgH rearrangements in BM and PB, whereas 6 dogs (35.3%) had no rearrangements in none of the samples. At T1, IgH monoclonal rearrangement was found in 13 (81%), 8 (50%) and 6 dogs (38%) in LN, PB and BM, respectively. At T0, the concordance rate between FC and PARR was 100%, 82% and 47% for LN, PB and BM, respectively. The highest concordance rate was obtained in LNs (PARR-positive/FC-positive), whereas the highest discordance was obtained in BM (PARR-positive/FC-negative). At T1, the concordance rate was overall reduced, accounting for 47%, 50%, and 63% in LN, PB and BM, respectively. The highest discordance rate was found in LNs (PARR-positive/FC-negative), whereas the highest concordance was found in BM (PARR-negative/FC-negative). Discussion We propose the use of both, PARR and FC, in tandem to offset the possibility of false-negative MRD assessment; in case of discrepant results, dogs should be closely monitored to detect a possible early recurrence. The concordance rate was largely dependent on the time point, being higher in T0. The discordance between PARR and FC results in dogs in clinical remission may be due to the limited number of available cells, which reduces the sensitivity of FC.Pubblicazioni consigliate
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