Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study

Abstract

Key Points• Translocation t(11;14) confers a favorable prognosis in AL amyloidosis patients treated with HDM.Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This longterm follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P 5 .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P 5 .05) and a trend for better overall survival (median, not reached vs 93.7 months; P 5 .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations. (Blood. 2016;128(4):594-602)

Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma

“…Conversely, rs10507419 was strongly associated with the IgG profiles while weakly opposite associations were found with this SNP and the LCO profiles. rs10507419 on chromosome 13q13.2 maps close to the NBEA locus (13q13.3) which is a fragile site causing deletion of the telomeric end of chromosome 13q in patients with MM, MGUS and AL-amyloidosis 22,[27][28][29] . We found in Hi-C data that rs10507419 shows long-range association with the NBEA locus.…”

Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry

“…Of 701 AL S patients, 463 (66%) had dFLC levels available at diagnosis. Finally, because bone marrow FISH has been associated with organ involvement and prognosis in AL S , [18][19][20] we examined whether there was any differential IGVL gene usage according to bone marrow FISH.…”

Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis

“…This raises the possibility that bortezomib may abrogate the poor prognosis of high-risk aberrations [44]. However, these high-risk cytogenetic aberrations may confer an unfavorable prognosis in HDM-treated patients [45]. …”

“…In a study assessing the prognosis of AL amyloidosis patients treated with high-dose melphalan (HDM) chemotherapy and ASCT, HDM was found to be safe, with only 1 out of 123 patients dying because of the treatment, and with a complete remission (CR) rate of 34%. Patients harboring t(11; 14) had an improved CR rate, translating into a prolonged event-free survival [45]. …”