Abstract

Introduction

AL amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils accumulated in different organs. Translocation (11;14) (t(11;14)) is seen in about half of AL patients, but the clinical significance is still unknown. So our study has focused on the chromosome aberration of t(11;14). We report the relationship between the chromosome aberration and the organ response, the organ involvement which greatly influence prognosis of AL patients. Furthermore, we examined the prognosis and treatment response to compare t(11;14) influences of AL with t(11;14) influences of multiple myeloma (MM).

Patients and Methods

We analyzed in AL and symptomatic MM patients have t(11;14) using fluorescence in situ hybridization from January 2010 to December 2014 in Japanese Red Cross Medical Center. We examined the overall survival and the therapy response rate. In addition, we compared t(11;14)-positive and negative in AL and MM respectively. Besides, we investigated the involved organ parts and the organ response with melphalan and dexamethasone (MD) therapy in AL. Outcome was assessed based on remission after three months and one year. Remissions were determined according to consensus criteria in 2011 for AL and IMWG uniform criteria for MM. Survival distribution of OS was estimated using the Kaplan-Meier method and compared using the log-rank test. Data between t(11;14)-positive and negative were compared with the Mann-Whitney U test or X2 test. The statistical analysis was performed using IBM SPSS statistics ver.23.

Results

Among 27 patients with AL, 9 cases were t(11;14)-positive patients (age median, 64yr; range, 37-80), and 13 out of 46 were positive in MM (age median, 64yr; range, 34-86). (excluded complication of both AL and MM cases) In AL cases, the t(11;14)-positive group tended to shorter overall survival (OS) than negative cases. On the other hand, in the patients with MM, positive group tended to superior OS to negative (AL: P=0.442(Fig.1A), MM: P=0.327(Fig.1B)).

Compared with t(11;14)-negative AL group, t(11;14) positive group was tended to have much organ involved numbers of amyloid protein (67% v 34%; P=0.109) and much cardiac involvement patients (67% v 39%; P=0.171). On the other hand, there were little cardiac and renal response in both t(11;14)-positive and negative with MD therapy after 3 months (heartF17% v 0% P=0.462/renalF0% v 0%).

In MM patients, ORR after 3 months were 67% and 79% in t(11;14)-positive and negative cases respectively (P=0.386). That after 1 year were 78% and 74% respectively (P=0.889).

Conclusion

t(11;14) is important prognostic factor and showed conflict prognosis between AL and MM. From this investigation, the importance of connecting the chromosome abnormality every disease was shown. In addition, our investigation recognized tendencies that the amyloid involvement rate to the heart was high, and the cardiac response with MD therapy were low in AL t(11;14)-positive group. As these results, we thought that t(11;14)-positive AL patients' OS were shortened. The significant difference did not appear in this examination while these tendencies were clearly accepted in little number of patient cases. Further investigation using rather number of patient samples is needed.

In conclusion, the cardiac amyloid involvement is high in the AL t(11;14)-positive group, and the cardiac response by MD therapy is low. We should have doubt eyes of the amyloid involvement to the heart in AL t(11;14)-positive patients, and have the posture that can support cardiac amyloidosis immediately. In addition, breakthrough new treatments are expected urgently for AL patients.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.