The degrees of plasma cell clonality and marrow infiltration adversely influence the prognosis of AL amyloidosis patients.
OBJECTIVE
Primary amyloidosis is a lethal form of plasma cell (PC) dyscrasia characterized by deposits of monoclonal immunoglobulin light chains that cause organ dysfunction. In contrast to multiple myeloma, the amyloid clone is typically indolent and of small size, and marrow PC clonality is not always apparent. This is generally investigated by analyzing the light chain isotype ratio in bone marrow PC. We investigated whether the degree of PC infiltration (PC%) and clonality (PC isotype ratio) affected survival in 56 consecutive patients with primary amyloidosis.


METHODS
PC% was determined by morphologic examination. Immunofluorescence microscopy was used to determine the PC light chain isotype ratio. Statistical analysis was carried out using Cox regression models.


RESULTS
The degrees of PC clonality and infiltration were inversely correlated with survival (PC isotype ratio, p = 0.001; PC%, p = 0.008). The two variables were weakly correlated (p = 0.02; r = 0.3). Bone marrow PC isotype ratio demonstrated a powerful independent prognostic value at multivariate analysis when analyzed together with congestive heart failure (the major known negative prognostic factor) and PC%. k/l ratio cut-off values of 0.2 (l patients, p = 0.022) and 16 (k patients, p = 0.03) discriminated two groups with a similar number of patients and significantly different survivals.


CONCLUSIONS
PC clonality and marrow infiltration are important parameters that influence prognosis, presumably because they reflect the amount of pathogenic light chain synthesis.
Perfetti
V
V
Biotechnology and Organ Transplantation Research Laboratories, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
Colli Vignarelli
M
M
Anesi
E
E
Garini
P
P
Quaglini
S
S
Ascari
E
E
Merlini
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000235:genetics; D000686:Amyloidosis / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis
D000682:Amyloid; D007147:Immunoglobulin Light Chains