Excessive Weight Gain during Mobilization Increases First Year Mortality Following High Dose Therapy and Stem Cell Transplantation in Patients with Primary Amyloidosis.
Authors: Leung Nelson , Leung Tessa R. , Dispenzieri Angela , Lacy Martha Q. , Gertz Morie A. 
Published: October 2019

Introduction: High dose melphalan followed by stem cell transplantation (HDM-SCT) is currently the most effective therapy for primary systemic (AL) amyloidosis. Recent data showed a 40% complete hematologic response rate and median survival of 4.6 years with HDM-SCT can be obtained. Despite its advantages, treatment mortality can be excessive in high-risk patients. Previously, extensive cardiac, hepatic or renal involvement had been identified as risk factors for poor outcome. We observed that patients who had more than 2% weight gain during mobilization also had a poorer survival after HDM-SCT. This study was undertaken to further examine the outcome of these patients.

Patients: Consecutive patients who underwent HDM-SCT for AL between 7/97 and 6/04 were retrospectively studied. Weight (kg) was measured just prior to mobilization, at its peak during mobilization and collection, and just prior to conditioning. Baseline characteristics were extracted from medical records along with left ventricular ejection fraction (LVEF), septal thickness, glomerular filtration rate (GFR), proteinuria, alkaline phosphatase, and the number of visceral organ involved with AL. Mobilization was achieved by cyclophosphamide (C) with granulocyte colony growth factor (GCSF), C with granulocyte-macrophage colony stimulating factor (GMCSF), GCSF alone and GMCSF alone or in combination with GCSF. Patients were conditioned with melphalan in doses of 100mg, 140mg or 200mg per m2 or 140 mg/m2 in combination with total body irradiation. Hematologic response was determined by A 50% reduction in measurable monoclonal protein levels or complete eradication by immunofixation if too small to quantify.

Results: During the time period, 128 patients underwent HDM-SCT for AL. One patient was excluded because no weight was recorded during mobilization and 1 refused consent. Weight gain of 2% or greater was noted in 51.6% (65) of the patients. Mortality at 1 year was significantly higher in patients with > 2% weight gain (32.3%) compared to those without (9.8%) (OR = 4.37, 95% CI 1.71 to 12.77, p = 0.004). Univariate analysis identified septal thickness, GFR, alkaline phosphatase, organ involvement and weight gain as risk factors of mortality at 1 year. Using the logistic model, only septal thickness (p =0.04), GFR (p = 0.009) and weight gain (p = 0.009) remained independent predictors of first year mortality in the multivariate analysis. No association was found between weight gain and mobilization regimen. Analysis of patient who survived the first 100 days posttransplant showed no correlation between weight gain and hematologic response. Finally, weight reduction to baseline prior to conditioning did not improve first year survival for those who gained > 2% during conditioning.

Conclusion: Our study found weight gain of 2% or more was associated with significantly higher first year mortality after HDM-SCT. The effect of weight gain was independent of both cardiac and renal involvement with AL. Fluid retention was not directly responsible for the higher mortality, as weight reduction to baseline failed to improve the outcome of these patients. Weight gain during mobilization appears to be a novel pretransplant risk factor that predicts the outcome of HDM-SCT based on response to mobilization.