Leung, Tessa R.

Abstract 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.

AbstractHigh-dose melphalan followed by stem cell transplantation (HDM-SCT) has become the treatment of choice for patients with immunoglobulin light chain amyloidosis (AL). Unfortunately, treatment mortality can be excessive in certain subpopulations. We have noted that patients who gained more than 2% body weight during mobilization had a poorer outcome following HDM-SCT. Excluding 2 patients for lack of weight record and denial of consent, 126 patients between July 1997 and June 2003 were retrospectively studied. Weight increased more than 2.0% during mobilization in 51.6% of the patients. Patients who accumulated more than 2.0% tended to have more proteinuria, more organs involved, lower serum albumin, more diuretic use, and dosage adjustment during mobilization. First-year mortality was significantly higher in those with more than 2% weight gain (33.9% versus 9.8%, P = .002). Multivariate analysis showed weight gain, glomerular filtration rate, and septal thickness to be independent predictors of first-year mortality. The increase in mortality was noted even after the excess weight was diuresed prior to conditioning. The impact on mortality dissipated after the first year. Weight gain during mobilization appears to be a new marker of adverse outcome following HDM-SCT. Better prognostication may improve the treatment mortality rate of these patients.