Minimal Residual Disease as a Possible Predictive Factor for Relapse in Patients With AL Amyloidosis

This protocol will assess patients with AL amyloidosis who achieve a complete response (CR) or very good partial response (VGPR) to therapy for minimal residual disease (MRD). Three approaches to MRD testing will be used since there is no established method. The investigators will clone and sequence each patient's light chain (LC) gene and design patient-specific primers to evaluate genomic DNA from future marrow specimens. Whole genome sequencing (WGS) will be used to test baseline and follow-up marrow cell DNA, seeking copy number variations in chromosomes 1 and 2 or 22, and structural variations in chromosomes 11 and 14, consistent with the known genetic abnormalities in AL and with clonal LC gene use. Plasma protein analysis by mass spectrometry will also be used to look for fragmentary protein sequences associated with the culprit LC gene of each subject. The feasibility and predictive value of these three approaches in patients achieving CR or VGPR will be evaluated. This protocol will help provide insight into the ways that the disease changes and progresses. MRD testing is likely an important next step in AL management.

Sex

All

Inclusion Criteria:

* Patients with AL amyloidosis at Tufts Medical Center who have baseline bone marrow samples available and achieve a CR or VGPR to treatment. Patients may consent and register at diagnosis and have a baseline marrow collected at the time of consent; or patients may consent during therapy prior to achieving a response, if they have previously banked marrow cells for research.

Exclusion Criteria:

* Patients who do not have available baseline bone marrow samples.

• BACKGROUNDAbraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA, Gertz MA, Fonseca R. Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood. 2003 May 15;101(10):3801-8. doi: 10.1182/blood-2002-09-2707. Epub 2002 Dec 19. PMID 12515719
• BACKGROUNDPerfetti V, Casarini S, Palladini G, Vignarelli MC, Klersy C, Diegoli M, Ascari E, Merlini G. Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood. 2002 Aug 1;100(3):948-53. doi: 10.1182/blood-2002-01-0114. PMID 12130507
• BACKGROUNDBodi K, Prokaeva T, Spencer B, Eberhard M, Connors LH, Seldin DC. AL-Base: a visual platform analysis tool for the study of amyloidogenic immunoglobulin light chain sequences. Amyloid. 2009 Mar;16(1):1-8. doi: 10.1080/13506120802676781. PMID 19291508
• BACKGROUNDComenzo RL. Plasma cell neoplasms, their precursor States, and their prediction of organ damage. J Clin Oncol. 2014 Sep 1;32(25):2679-82. doi: 10.1200/JCO.2014.56.2892. Epub 2014 Jul 14. No abstract available. PMID 25024079
• BACKGROUNDComenzo RL, Wally J, Kica G, Murray J, Ericsson T, Skinner M, Zhang Y. Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid-related organ involvement and survival after stem cell transplantation. Br J Haematol. 1999 Sep;106(3):744-51. doi: 10.1046/j.1365-2141.1999.01591.x. PMID 10468868
• BACKGROUNDComenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood. 2001 Aug 1;98(3):714-20. doi: 10.1182/blood.v98.3.714. PMID 11468171