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Dr. Gertz - Transplantation for Immunoglobulin Light Chain Amyloidosis. A Statistical Analysis of Factors Predicitng Outcome In Over 400 Patients
Morie Gertz, MD
Mayo Clinic
Rochester, Minnesota
USA
12.02.10

Morie Abraham A. Gertz, MD1, Martha Lacy, MD2, Angela Dispenzieri, MD2, Shaji Kumar, MD2, Francis Buadi, MD2, David Dingli, M.D., Ph.D.2, Stephen M. Ansell, MD, PhD3, Dennis Gastineau, MD2, David James Inwards, MD4, Patrick B Johnston, MD, PhD5, Mark R. Litzow, MD4, Ivana Micallef, MD2, Luis Porrata, MD4, Nelson Leung, MD6, Robert Wolf, PharmD, RPh7, William J Hogan, MBBCh2 and Suzanne R. Hayman, MD2

1Hematology, Mayo Clinic, Rochester, MN
2Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
3Division of Hematology, Mayo Clinic, Rochester, MN
4Mayo Clinic, Rochester, MN
5Department of Medicine/Division of Hematology, Mayo Clinic, Rochester, MN
6Dept. of Nephrology, Mayo Clinic, Rochester, Rochester, MN
7Pharmacy, Mayo Clinic, Rochester, MN

Introduction: Autologous stem cell transplantation for patients with amyloidosis results in high reported hematologic and organ response rates compared with conventional chemotherapy. 

Patients: Four-hundred and thirty-four patients have undergone transplantation between March 8, 1996, and April 13, 2010 Table 1. Clinical parameters seen in patients with amyloid are given in Table 2.  .  The overall day-100 mortality seen in this group of patients is 44 of 434 patients (10%).

Results: The most important determinant of outcome is stage defined by BNP and troponin levels.  Figure 1 demonstrates the survival for patients for all 3 cardiac stages.  Troponin <.035;  NT-proBNP <332. Stage 1 both low, Stage 3 both elevated. The survival of all patients based on whether they achieved a complete response, a partial response (>50%), or no response was analyzed.  Median survival has not been reached for the complete response group, is 107 months for the partial response group, and is 32 months for the no response group (p<0.0001).   Figure 2, divides the patients at the median dFLC level of 13.5 mg/dL demonstrating that for patients with a higher level of free light chain, the median survival is 87.6 months and has not been reached for those with a lower level of free light chain.  A proportional hazards model for variables that impact on survival was done in all patients, and the only relevant predictor of outcome was stage (p<0.0001).  When the same analysis was performed using a landmark of 6 months, the only predictor of outcome was stage (p=0.0005).  When best response was incorporated into the landmark model, it was the strongest predictor of survival.  The amyloid stage predicted survival (p= 0.0005), and the best response to therapy (p <0.0001).  When the same analysis was performed in the entire group of 434, stage and best response each remained significant (p<0.0001).

Discussion: There is a high response rate associated with high-dose therapy that was not observed in the melphalan and prednisone era.  For eligible patients who can be transplanted safely, high-dose melphalan is an effective therapy for many patients with amyloidosis.  Best response and stage at diagnosis are the best predictors of overall survival.

 

Table 1. Characteristics of Patients with Amyloidosis Prior to Autologous Stem Cell Transplant (n=434)

Number

Percentage (%)

Sex M/F

259/175

60

Renal involvement

304

70

Cardiac involvement

214

49

Peripheral nerve involvement

54

12

Liver involvement

59

14

Autonomic involvement

15

3

CTS

54

12

Tongue enlargement

44

10

Number organs involved:

    1

203

47

    2

168

39

    >2

63

14

Table 2. Laboratory Values in Patients with Amyloidosis (n=434)

Units

Median

Interquartile Range(IQR)

Liver edge N=59

cm BCM

7

(4-10)

Albumin

g/dL

2.7

(1.9-3.3)

Creatinine

mg/dL

1.1

(0.9-1.3)

Cholesterol

mg/dL

241

(185-336)

Alkaline phosphatase

U/L

88

(70-129)

Β2 Microglobulin

mg/L

2.59

(2.08-3.04)

24-hour urine total protein

g/day

3.68

(0.28-7.45)

% Marrow PC

7

(3-13)

IVS septal thickness

mm

12

(10-14)

EF

%

65

(60-69)

Age

years

57

(51-63)

Months from diagnosis to SCT

4

(3-7)

Figure 1: Survival by amyloidosis stage I-top, II-middle

III-bottom

Figure 2: Survival by the pretreatment d FLC greater than or less than13.5 mg/dL.

Top line <13.5, bottom >=13.5


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