Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis.
OBJECTIVE
To determine whether bone marrow (BM) angiogenesis progressively increases along the spectrum of plasma cell disorders ranging from monoclonal gammopathy of undetermined significance (MGUS) to advanced myeloma.


METHODS
Four hundred patients with the following disorders were studied: MGUS (76 patients); smoldering (indolent; early-stage) multiple myeloma (SMM; 112 patients); newly diagnosed, active multiple myeloma (MM; 99 patients); relapsed (advanced) multiple myeloma (RMM; 26 patients); and primary amyloidosis (AL; 87 patients). Forty-two normal control BM samples were studied for comparison. BM angiogenesis was studied in a blinded manner by immunohistochemical staining for CD34 to identify microvessels.


RESULTS
The median (range) microvessel density (MVD) per x400 high power field was 1.3 (0-11) in the controls, 1.7 (0-10) in AL, 3 (0-23) in MGUS, 4 (1-30) in SMM, 11 (1-48) in newly diagnosed MM, and 20 (6-47) in RMM; P < 0.001. MVD was significantly higher in MGUS, SMM, newly diagnosed MM, and RMM compared with controls and AL; P < 0.001. MVD was not significantly different between controls and AL. By grading, high-grade angiogenesis was present in 0% of controls and AL, 1% of MGUS, 3% of SMM, 29% of newly diagnosed MM, and 42% of RMM; P < 0.001. MVD correlated with the BM plasma cell labeling index (rho = 0.46, P < 0.001) and BM plasma cell percentage (rho 0.5, P < 0.001). Survival was 28 months in SMM and newly diagnosed MM with high-grade angiogenesis, compared with 53 months for those with low- and intermediate-grade angiogenesis; P = 0.02.


CONCLUSIONS
BM angiogenesis progressively increases along the spectrum of plasma cell disorders, from the more benign MGUS stage to advanced myeloma, indicating that angiogenesis may be related to disease progression.
Division of Hematology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. rajks@mayo.edu
S Vincent
SV
Rajkumar
Ruben A
RA
Mesa
Rafael
R
Fonseca
Georgene
G
Schroeder
Matthew F
MF
Plevak
Angela
A
Dispenzieri
Martha Q
MQ
Lacy
John A
JA
Lust
Thomas E
TE
Witzig
Morie A
MA
Gertz
Robert A
RA
Kyle
Stephen J
SJ
Russell
Philip R
PR
Greipp
D000686:Amyloidosis / Q000150:complications* / Q000628:therapy; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D009101:Multiple Myeloma / Q000150:complications* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010265:Paraproteinemias / Q000150:complications* / Q000628:therapy; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D001613:beta 2-Microglobulin / Q000378:metabolism
D018952:Antigens, CD34; D001613:beta 2-Microglobulin