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Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation.

ABSTRACT: The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic immunoglobulin light chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs 44%; P=0.01), less renal involvement (55% vs 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs 32%; P<0.0001) compared to those with a Low plasma cell proliferative index. Both progression-free survival and overall survival were lower in patients with an Elevated compared to Low plasma cell proliferative index: median progression-free survival 44 vs 95 months (P<0.0001) and median overall survival 102 vs 143 months (P=0.0003). All-cause mortality at 100 days was higher in patients with an Elevated plasma cell proliferative index (elevated 10.3% vs low 4.3%; P=0.008). On multivariate analysis Elevated plasma cell proliferative index was an independent prognostic factor for overall survival (Hazard Ratio 1.5, 95%CI: 1.1-2.1; P=0.021). The plasma cell proliferative index is an important prognostic tool in patients with AL amyloidosis undergoing stem cell transplant.

SUBMITTER: Sidiqi MH

PROVIDER: S-EPMC6029535 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation.

Sidiqi M Hasib MH Aljama Mohammed A MA Jevremovic Dragan D Morice William G WG Timm Michael M Buadi Francis K FK Warsame Rahma R Lacy Martha Q MQ Dispenzieri Angela A Dingli David D Gonsalves Wilson I WI Kumar Shaji S Kapoor Prashant P Kourelis Taxiarchis T Leung Nelson N Hogan William J WJ Gertz Morie M

Haematologica 20180419 7

The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic immunoglobulin light chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1<sup>st</sup> January 2003 and 31<sup>st</sup> August 2016. Two cohorts were identified according to Low or E ...[more]

PMID: 29674497

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Project description:The prognostic impact of increased beta-2 microglobulin (B2M) in patients with light chain (AL) amyloidosis undergoing autologous stem cell transplantation (ASCT) is unknown. The Mayo 2012 stage and increased bone marrow plasma cell (BMPC) percentage are known predictors for survival. Increased B2M is predictive of survival in patients with multiple myeloma. We evaluated the prognostic role of B2M in patients with newly diagnosed AL undergoing ASCT. We retrospectively reviewed patients with a diagnosis of AL amyloidosis who were treated with ASCT between July 1996 and September 2017. Patients with a creatinine level >1.2 mg/dL were excluded, because that affects B2M levels. The receiver operator characteristic curve was used to determine the best cutoff for B2M before ASCT in predicting survival, which was 2.5 µg/mL, which was also the upper limit of normal in our laboratory. Baseline characteristics were compared between patients with B2M >2.5 µg/mL and ≤2.5 µg/mL. Progression-free survival (PFS) was defined as the time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from the time of ASCT to death of any cause. Univariate and multivariate analyses were done for OS. Five hundred and ten patients were identified, 222 of whom (44%) had a B2M >2.5 µg/mL. These patients were more likely to be older (median age, 61 versus 57 years; P = .0002), to have Mayo 2012 stage III/IV disease (33% versus 8%; P < .0001), to have more than 2 organs involved (25% versus 14%; P = .001), and to have ≥10% BMPCs (56% versus 40%; P = .0002) compared with patients with B2M ≤2.5 µg/mL. The median PFS and OS were shorter in patients with B2M >2.5 µg/mL (median PFS, 64 months versus 80 months [P = .03]; median OS, 104.9 months versus 175.5 months [P < .0001]). On univariate analysis, predictors for OS included age >60 years (hazard ratio [HR], 1.61; P = .001), Mayo 2012 stage III/IV (HR, 3.36; P < .0001), more than 2 organs involved (HR, 1.36; P = .07), ≥10% BMPCs (HR, 1.5; P = .005), melphalan conditioning with 200 mg/m2 (HR, .29; P < .0001), B2M >2.5 µg/mL (HR, 1.82; P < .0001), and transplantation during or after 2010 (HR, .4; P = .0006). On multivariate analysis, only Mayo 2012 stage III/IV (HR, 1.89; P = .005), melphalan conditioning with 200 mg/m2 (HR, .39; P < .0001), B2M >2.5 µg/mL (HR, 1.84; P = .003), and transplantation performed during or after 2010 (HR, .58; P = .03) remained independent predictors of OS. Our findings identify B2M >2.5 µg/dL before ASCT as an independent predictor for OS in patients with AL amyloidosis and normal kidney function and should be routinely measured.

Dataset Information

Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation.

Publications

Plasma cell proliferative index predicts outcome in immunoglobulin light chain amyloidosis treated with stem cell transplantation.

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