The Timing of Acute Renal Failure Strongly Affects Survival of Immunoglobulin Light Chain (AL) Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4120-4120
Author(s):  
Nelson Leung ◽  
Shaji Kumar ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  

Abstract Abstract 4120 Introduction: Autologous stem cell transplantation (ASCT) remains an effective treatment for immunoglobulin light chain (AL) amyloidosis but its high treatment related mortality is a concern. The development of acute renal failure can strongly affect the survival of these patients. This study looks at the impact of the timing of dialysis initiation on the overall survival (OS). Methods: AL patients who underwent ASCT from 3/96 to 1/10 were selected. Patients were placed into 4 groups: I - never dialyzed, II - initiated dialysis prior to ASCT, III - dialysis began within 30 days of ASCT and IV - dialysis was started after 30 days of ASCT. Results: Four hundred and ten patients were selected for study and 75 (18.3%) received dialysis. Baseline characteristics are listed in Table 1. In univariate analysis, serum creatinine (Scr) and b-2 microglobulin (b2m) were associated with dialysis post-ASCT. Both became non-significant in the multivariate model suggesting they are co-dependent. Dialysis had a strong influence on survival, p < 0.001 (Fig 1). This was most evident when dialysis was started after ASCT (group III (p = 0.003) and IV (p = 0.004)), but not before (II, p = 0.19).To explore the interactions of dialysis with cardiac biomarkers in their relationship with OS, cardiac troponins T (cTnT) and N terminal-pro-brain natriuretic peptide (NT-pro-BNP) were analyzed with timing of dialysis in a proportional hazard model. Timing of dialysis (p < 0.001), cTnT (p = 0.03) and NT-pro-BNP (p = 0.03) all were associated with OS. Using Receiver Operator Characteristic (ROC) curves, best cut points were chosen for cTnT (0.01 ng/ml) and NT-pro-BNP (1350 pg/ml) for survival. When treated as categorical variables, the proportional hazard model found that only NT-pro-BNP (p = 0.002) and timing of dialysis (p < 0.001) were independent predictors of OS but cTnT had loss its significance (p = 0.07). Using Kaplan Meier method, dialysis was a significant risk factor in patients with low cTnT and both high and low NT-pro-BNP (p < 0.001) but not in patients with elevated cTnT (p = 0.25). Discussion: The timing of acute renal failure strongly affects the OS of AL patients undergoing ASCT. In our study, patients who started dialysis prior to ASCT did not have an inferior OS compared to patients who never needed dialysis. On the other hand, starting dialysis after ASCT significantly shortened OS. The timing of dialysis was an independent predictor of OS even when combined with cardiac biomarkers. NT-pro-BNP appears to be the stronger marker when timing of dialysis is considered in the multivariate analysis. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1120-1120
Author(s):  
Michael Rosenzweig ◽  
David C. Seldin ◽  
Daniel G Remick ◽  
Martha Skinner ◽  
Karen Quillen ◽  
...  

Abstract Systemic AL amyloidosis is a clonal plasma cell disease related to multiple myeloma characterized by the wide spread deposition of amyloid fibrils into tissues and organs. Treatment for this disease is directed towards reducing amyloidogenic monoclonal light chains by attacking the underlying plasma cell dyscrasia. Aggressive treatment with high dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) is effective in inducing hematologic and clinical remissions and in extending survival. Tandem cycles of HDM/SCT have been shown to increase hematologic complete response (HCR) rates in patients with multiple myeloma and have therefore been included in the treatment of AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at Boston University Medical Center were treated with a second cycle of HDM/SCT after failing to achieve a HCR following a first transplantation. Eleven of 57 patients (19%) treated with tandem transplantation developed a high fever; 12-24 hours following melphalan administration. Other clinical features noted in some of the patients include hypotension, acute renal failure, and skin rash. Among the 11 patients described, there were 7 men and 4 women. The average age was 53.5 years (range 41-60). The average peak temperature of the 11 patients was 39.1º C (range, 38.1-39.4°C). All patients experienced resolution of fever within 24–48 hours. Six of the 11 patients developed a rash and 5 developed hypotension that was responsive to intravenous fluids or pressors when indicated. Two of the patients developed acute renal failure that improved following resolution of the fever. In all 11 patients, workup for an infectious etiology of fever was negative. One of the 11 patients described, had cytokine measurements before, during and after the febrile reaction. The concentration of several pro-inflammatory as well as anti-inflammatory cytokines increased significantly. IL-6, a classic endogenous, pyrogenic cytokine, increased 10 fold with this reaction demonstrating a clear physiologic response correlating with the clinical findings. Therefore, an unusual febrile reaction mediated by pyrogenic cytokines can occur in patients with AL amyloidosis exposed to a second cycle of high dose melphalan. While this reaction has not been observed in patients with multiple myeloma treated in similar fashion for unclear reasons, clinicians should be aware of this phenomenon we have termed a “melphalan recall” reaction in patients with AL amyloidosis treated with tandem cycles of HDM/SCT.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3468-3468
Author(s):  
Maria V Irazabal ◽  
Aflonso Eirin ◽  
Morie Abraham A. Gertz ◽  
Angela Dispenzieri ◽  
Shaji Kumar ◽  
...  

Abstract Abstract 3468 Engraftment syndrome (ES) is a complication of hematopoietic stem cell transplantation classically characterized by fever, rash, diarrhea, weight gain and non-cardiogenic pulmonary edema. Renal failure has been observed but is not considered to be a major part of the syndrome. We have noted that acute renal failure (ARF) is common around the time of leukocyte engraftment in light chain amyloidosis (AL) patients after autologous stem cell transplant (ASCT). We suspect this is due to ES and this retrospective review was conducted to further study this entity. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine (Scr) > 0.5 mg/dl within 4 days of leukocyte engraftment were selected. Patients who carried a diagnosis of ES were also included regardless of Scr elevation. Nephrotoxic insults were reviewed. Vitals were collected. Forty-one patients met criteria. Four patients were found not to have ES, 2 sepsis, 1 allergic interstitial nephritis (AIN), 1 acute cellular rejection. ES was noted in 37 (9.8%) patients, 2 presented with mainly pulmonary ES and 8 had both pulmonary and renal involvement. The degree of renal failure varied from mild and self-limited to severe and requiring dialysis. The renal failure is usually preceded by fever, rash, increasing edema, relative hypotension and low urine sodium (Figure 1). Treatment with glucocorticoids (60 mg/d) was successful in reversing the renal failure in most patients but those with pulmonary involvement required higher doses. Our study showed that ES presents more commonly with renal failure than pulmonary involvement in AL patients. Further complications may be prevented by early treatment with corticosteroids once infection is ruled out. Dosing depends on concurrent pulmonary findings. Distinguishing ES with AIN is difficult as presentations are similar but AIN will continue until the offending drug is removed while ES generally responds quickly to steroids alone. Figure 1. Figure 1. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.


2003 ◽  
Vol 63 (5) ◽  
pp. 1868-1873 ◽  
Author(s):  
Amit Fadia ◽  
Liam F. Casserly ◽  
Vaishali Sanchorawala ◽  
David C. Seldin ◽  
Daniel G. Wright ◽  
...  

2015 ◽  
Vol 15 ◽  
pp. e173
Author(s):  
S.K. Toprak ◽  
P. Ataca ◽  
E. Atilla ◽  
S.C. Bozdag ◽  
M.K. Yuksel ◽  
...  

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