,
,
A Palumbo1, SV Rajkumar2, MA Dimopoulos3, PG Richardson4, J San Miguel5,
B Barlogie6, J Harousseau7, JA Zonder8, M Cavo9, M Zangari6, M Attal10, A Belch11,
S Knop12, D Joshua13, O Sezer30, H Ludwig14, D Vesole15, J Blade16, R Kyle17, J Westin18,
D Weber19, S Bringhen1, R Niesvizky20, A Waage21, M von Lilienfeld-Toal22, S Lonial23,
GJ Morgan24, RZ Orlowski25, K Shimizu26, KC Anderson4, M Boccadoro1, BG Durie27,
P Sonneveld28 MA Hussein29
1 - , . . , ,
; 2 - , , ; 3 ­
, , , ; 4 ­
, , , ; 5 ­
, , ,
, ; 6 ­ /, ,
- , , ; 7 ­ ,
, , ; 8 ­ -,
, , , 9 ­
() , , ; 10 ­
, , ; 11 ­
, , , ; 12 ­ -
, , ; 13 ­ ,
, , ; 14 ­ 1- ,
, , , ; 15 ­ ,
. , -, ; 16 ­
, , IDIBAPS
, , ; 17 ­ , ,
, , ; 18 ­ ,
. , , ; 19 ­ /, ..
, , ; 20 ­ ,
, ,
- ­ , -, ; 21 ­
, . , , ; 22 ­
, - , ,
; 23 ­ -, ,
, , ; 24 ­ ,
- , , ; 25 ­
/ , , ; 26 ­
, . , , ; 27 ­
, -, ; 28 ­
, , ; 29
­ , -
, , , 30
­ , , .
INTERNATIONAL MYELOMA FOUNDATION
12650 Riverside Drive, Suite 206, North Hollywood, CA 91607-3421 USA
Tel: 818-487-7455
Fax: 818-487-7454
Email: TheIMF@myeloma.org
Website: www.myeloma.org
TRANSLATION FROM ENGLISH TO RUSSIAN PROVIDED COURTESY OF CELGENE RUSSIA.
2
()
1%, .
(), ,
,
. ,
,
(), .

.
, /,
, ,
, (, ,

),
,



.
.
, ,
,
. ,
. ,
/ ,
( 40 ).
,
.

2 ­ 3, .

,
,
.

.
: , , , , .
Leukemia 2008; 22:414-423.

() -
() ­
().
1%, 0.5% 0.7% (1).
7% (2). , ,
(MM), (3).
.
3
.

.

­ ,
2% 55 5% 65 (1).
, , :
71%,
(4). ,

.
(5 ­ 9).
(, ),
, (),
, /
. ,
, III, C S,
, V,
(G20210A) (9).
, ,
. , ,
( , , 3 ) ,
, ,
, ,
( )
(6) ( 1). 1,
2 40 .

.
4

7 ­ 10 .
28 (3).
.
/ ,
1 6, .
, XII X.

,
X VII (10, 11).
4.1 ,
­ 6.5 .
.
3 58.2,
13.4,
(6). , , -
, , ,
.

0.2%, - 0.9%,
- 4.2% (12, 13). ,
,
, ­ , 3 ,
,
(14).
/ (6).
5
40% (15 ­ 18).
(FDA)
, ,
,
(19). 3
5





-

,

(13.5 / ), ,
(10.5­11.5 /)
(20, 21). ,


, , .
1.
(6)




95%

95%

()
1.38
1.09­1.74


, /2
0.98
0.96­1.00



2.5
1.40­4.46
4.32
1.76­10.61


11.83
5.14­
5.55
1.57­19.58

27.23



1.57
1.18­2.08



3
1.19­7.56



5.17
2.78­9.59
3.04
1.25­7.38


18.44
11.48­29.64


90



7.98
4.49­14.18






21.72
9.44­49.93



7.67
4.69­12.53



6

9.9
3.89­25.18
6.53
2.11­20.23
+


6.9
3.92­12.17
4.05
1.93­8.52



15
6.07­37.09



11.67
5.07­26.86



41
2.48­677.92




17.5
9.25­33.10



20.5
7.51­55.93
12.69
4.06­39.66

11
1.42­85.20



: ­ , ­ , ­ .

310
() 44 6.1% (22).

65 , - 16 / .
174 7.5%,
6 .
, 8 , ­ 27
(27). , ,
,
,
. ,
3% (24) 10% (23). ,
, 4
3­4% ,
(24), / (25, 26).
- 10% (23).
, , . ,
, ,
.
7
, ,
(27). ,

, -6 (28).
VIII,
S (29). ,

, .

,
/. ,
. ,
, ,
, , .
: 3­4% (30,
31), / 2­4% (32­34).

14­26% (24, 35, 36),
/ ­ 2­8% (37, 38).
, /
/, 17%,
- 3%.
(24).
10-20% (25, 26, 39),
/ - 11% (40).
III ,
12­20% ,
(25, 26).
10­27% (41-43),
­ 58% (44). 2
24­26, 30­53). ,
8

,
(54). , 3 .
.

Zangari et al. (63) ,
, 535 ,
, .
, 15%.

4.3 ,
2.5 , /
.
(64).

­ , ,
.
(55, 56). ,
,
75% (57),
/ - 8­16% (59, 60) ( 2).
, -
,
8­16 4%, (59, 60).
14%
(61).
/ (62).
2. ,
, .

(480 )
9
(160 ); 23 8%, (58).
,
,
(23 5%) (65), ,
(31 14%) (54).
2.



/

(%)

(%)



3­4a
30,31
2­4
32­34

14­26
24,35,36
2­8
37,38


10­20
25,26,39
11
40

10­27
41­43
58b
44


3b­11
45,46
4­8
47­50


16­34
51,52
15
53





0­33
55,56

8­75
57,58
8­16
59,60




14
61




0
62
: ­ , ­ .

b ,


(66, 67),
.
40 ,
. - (68),
9
,
10
,





.
, ,
,
,
.







3, 2 2 , .
(MEDENOX), 1102
(69). ,
40 , , (5.5
14.9%, P<0.001). 3706
(70); (2.8
5.0%, P=0.002). 849
(71). -,
(5.6 10.5%, P=0.03).

. - 8 ,
()
(72),
,
, ,
( 0.48; 95% , 0.23­1.00).
(73)


(74).





,





,
,
, ,
.
,
(74).
11
,
, , -

,
(75). 17 444 ,
,
160 . 1.6% ,
, 2.5% , ,
(76).


,




.


,
, (69
­ 71). ,
MEDENOX ,
( 0.50, 95% 0.14­1.72) (77).
(78) 311
IV
, .
1 6 ,
() 1.3­1.9.
4% , , 0.6% ,
.
6 ( = 0.03). .
,
. -,
, ­
, , . -,
(4%)
12
. -,
P-450 CYP2C9

(79). ,
.
,

,
, ,
.

( 3).
,
26%. ,
(1.25 ),
13% (35). ,
; 25%
(31). 26 ,
,
, ( 2.0-3.0), 8% (80).

, . 65 ,
, 20%,
40 4
3%. 2
(25). 412
­ ­ ­
­ . , ,
. 5% 9%
, 6 (81).
50 ,
13
,
(1.25 ), 14% (82).
105 , ,
, - ;
58%. , 58
(81 ), 18% (44).
256
( , , ,
, ) .
, ,
14%, , , - 34%. ,
, (1
), 31%, , ,
(40 ), - 15% (83). 162
, ,
, , , 34% 18%.
,
24%,
15% (51).
,
, , ,
.
34 , ,
(80­325 ), 3% (84).

(480 )
(160 ); 23 8%, ,
- , 14 5%, ,
(58). ,
,
,
. ,
14
( 100 ), 5%
(85). ,
85% ;
9% (81 ) (86). ,

.
: , (325 ) ,
, , 81 ­ 162 ,
(87).
, , ,
.

, , ,
,
(88, 89).

(74).

.
, 2.0­
3.0, ,
, ,
. ,
. , ,
,
.



, .
,
.
15
3.


(%)











13­25
8

31,35,80

3



25

9
14

18
44,81,82

15­24
31

51,83







3­14
58,84




5
85




9
86
: ­ , ­ , ­ .
,

, .

, 10%.



5% (30,31,54). ,

,


,

. ,
,
,
(31,35,80), .
, ,
16
,
(25). ,
,
(44, 83).
,
(90).
,
24% (51).
. ,
,
. /

. (2­15%) ,
(3­34%).
.

,
.

, ,
, 10% (59,84­86).

, ,
.

,
, 4. ,
, 2 40.
,
.
17
4.
,




:

81 ­ 325






: (

40

)

(

2-3)







,



(
b
40 )

(

2-3)
: ­ , ­ .
­ 30 /2
b 480 .

, , , ,
, (, ,
), (
) ;
, , ,
;
18
, , ,
.
,
. ,
, .


, , ,
, .

, ,



, , ,
, ,
.
,
, .
, ,
.

, .
, , ,

­ ,
.
, ,
.
,
19
, (
) ,
.
40 1
5000 .
,
.
(< 30 ) ,
.
(91, 92).
.
12
(6).
6 , 12
(25,52,83).
4-6 , ­
, ­
.

.
.
, ,

.


,

,
,
. ,
. ,
-
, -
,
(93, 94).
20



, ,
. 25%
,
(95). ,
, , 50% (96).
,
95%.
.
­
.
. -
-





(97).


, ,
/ , .

.
. ­
100 / 12 200 / ; 1 / 12
1.5 / ; 86 / 12 171 /
.
, , .
6 , ,
2.0 3.0 .
.
21
, ,
10% (98).
,
, (99).
,
,
, ,
.
, ,
,

(81). ,
, ,
.

,
, , ,
. , ,
, ( ) .

, . ,

( 4).
, ,
.

, ( ,
),
( 40 )
( 2­3). , (
, ),
22
.
,
. - ,
, ,
10%.

1 Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ. Trends in the incidence of deep
vein thrombosis and pulmonary embolism. A 25-year population-based study. Arch Intern Med 1998; 158: 585­
593.
2 Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency
and characteristics. Thromb Haemost 2002; 87: 575­579.
3 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancy, prothrombotic mutations, and the risk of venous
thrombosis. JAMA 2005; 293: 715­722.
4 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Predictors of survival after
deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 1999; 159:
445­453.
5 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the
Sirius study. Arch Intern Med 2000; 160: 3415­3420.
6 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein
thrombosis and pulmonary embolism. Arch Intern Med 2000; 160: 809­815.
7 Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN et al. Relative impact of risk
factors for deep vein thrombosis and pulmonary embolism. Arch Intern Med 2002; 162: 1245­1248.
8 Ageno W, Squizzato A, Garcia D, Imberti D. Epidemiology and risk factors of venous thromboembolism.
Semin Thromb Hemost 2006; 32: 651­658.
9 Bauer KA. The thrombophilias: well-defined risk factors with uncertain therapeutic implications. Ann Intern
Med 2001; 135: 367­373.
10 Bick RL. Cancer-associated thrombosis. N Engl J Med 2003; 349: 109­111.
11 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol 2005; 6: 401­410.
12 Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J et al. A randomized clinical trial
evaluating tamoxifen in the treatment of patients with mode-negative breast cancer who have estrogenreceptor-
positive tumors. N Engl J Med 1989; 320: 479­484.
13 Fisher B, Dignam J, Wolmark N, DeCillis A, Emir B, Wickerham DL et al. Tamoxifen and chemotherapy for
lymph node-negative, estrogen receptor positive breast cancer. J Natl Cancer Inst 1997; 89: 1673­1682.
14 White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective
or urgent surgical procedures. Thromb Haemost 2003; 90: 446­455.
15 Bona RD. Thrombotic complications of central venous catheters in cancer patients. Semin Thromb Haemost
1999; 25: 147­155.
16 Bern MM, Lokich JJ, Wallach SR, Bothe Jr A, Benotti PN, Arkin CF et al. Very low doses of warfarin can
prevent thrombosis in central venous catheters: a randomized prospective trial. Ann Intern Med 1990; 112: 423­
428.
17 Monreal M, Alastrue A, Rull M, Mira X, Muxart J, Rosell R et al. Upper extremity deep venous thrombosis
in cancer patients with venous access devices-prophylaxis with low molecular weight heparin (Fragmin).
Thromb Haemost 1996; 75: 251­253.
18 Verso M, Agnelli G. Venous thromboembolism associated with long term use of central venous catheters in
cancer patients. J Clin Oncol 2003; 21: 3665­3675.
19 FDA Alert. Information For Healthcare Professional: Eyrthropoiesis Stimulating Agents (ESA) [Aranesp
(Darbopoietin), Epogen (Epoietin Alfa), and Procrit (Epoietin Alfa)]. Food and Drug Administration: Rockville,
MD, March 9, 2007. Accessed May
25, 2007, at http://www.fda.gov/cder/drug/InfoSheets/HCP/ RHE2007HCP.htm..
20 Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M et al. Correction of anemia with epoietin
alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085­2098.
23
21 Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D et al. Normalization of
hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355:
2071­2084.
22 Sallah S, Husain A, Wan J, Vos P, Nguyen NP. The risk of venous thromboembolic disease in patients with
monoclonal gammopathy of undetermined significance. Ann Oncol 2004; 15: 1490­1494.
23 Srkalovic G, Cameron MG, Rybicki L, Deitcher SR, Kattke- Marchant K, Hussein MA. Monoclonal
gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of
venothromboembolic disease. Cancer 2004; 101: 558­566.
24 Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR, Eastern Cooperative Oncology Group. Phase III
clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed
multiple myeloma: A clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006;
24: 431­436.
25 Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V et al. Oral melphalan and prednisone
chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple
myeloma: randomised controlled trial. Lancet 2006; 367: 825­831.
26 Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus
thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in
elderly patients with multiple myeloma (IFM 99-06): a randomized trial. Lancet 2007; 370: 1209­1218.
27 Zangari M, Saghafifar F, Mehta P, Barlogie B, Fink L, Tricot G. The blood coagulation mechanism in
multiple myeloma. Semin Thromb Hemost 2003; 29: 275­282.
28 Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of
clinical studies. Thromb Haemost 2005; 94: 362­365.
29 Auwerda JJA, Sonneveld P, de Maat MPM, Leebeek FWG. Prothromboic coagulation abnormalities in
patients with newly diagnosed multiple myeloma. Haematologica 2007; 92: 279­280.
30 Rajkumar SV, Gertz MA, Lacy MQ, Dispenzieri A, Fonseca R, Geyer SM et al. Thalidomide as initial
therapy for early-stage myeloma. Leukemia 2003; 17: 775­779.
31 Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for
previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16­19.
32 Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and
refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2
study of 169 patients. Blood 2001; 98:492­494.
33 Neben K, Moehler T, Benner A, Kraemer A, Egerer G, Ho AD et al. Dose-dependent effect of thalidomide
on overall survival in relapsed multiple myeloma. Clin Cancer Res 2002; 8: 3377­3382.
34 Schey SA, Cavenagh J, Johnson R, Child JA, Oakervee H, Jones RW. An UK myeloma forum phase II study
of thalidomide; long term follow-up and recommendations for treatment. Leuk Res 2003; 27: 909­914.
35 Cavo M, Zamagni E, Tosi P, Cellini C, Cangini D, Tacchetti P et al. First-line therapy with thalidomide and
dexamethasone in preparation for autologous stem cell transplantation for multiple myeloma. Haematologica
2004; 89: 826­831.
36 Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR et al. Combination therapy with
thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319­4323.
37 Anagnostopoulos A, Weber D, Rankin K, Delasalle K, Alexanian R. Thalidomide and dexamethasone for
resistant multiple myeloma. Br J Haematol 2003; 121: 768­771.
38 Palumbo A, Bertola A, Falco P, Rosato R, Cavallo F, Giaccone L et al. Efficacy of low-dose thalidomide and
dexamethasone as first salvage regimen in multiple myeloma. Hematol J 2004; 5: 318­324.
39 Dimopoulos MA, Anagnostopoulos A, Terpos E, Repoussis P, Zomas A, Katodritou E et al. Primary
treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with
multiple myeloma. Haematologica 2006; 91: 252­254.
40 Offidani M, Corvatta L, Marconi M, Olivieri A, Catarini M, Mele A et al. Thalidomide plus oral melphalan
compared with thalidomide alone for advanced multiple myeloma. Hematol J 2004; 5: 312­317.
41 Osman K, Comenzo R, Rajkumar SV. Deep venous thrombosis and thalidomide therapy for multiple
myeloma. N Engl J Med 2001; 344: 1951.
42 Schutt P, Ebeling P, Buttkereit U, Brandhorst D, Opalka B, Poser M et al. Thalidomide in combination with
vincristine, epirubicin and dexamethasone (VED) for previously untreated patients with multiple myeloma. Eur
J Haematol 2005; 74: 40­46.
43 Zervas K, Dimopoulos MA, Hatzicharissi E, Anagnostopoulos A, Papaioannou M, Mitsouli Ch et al. Primary
treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-
VAD doxil): a phase II multicenter study. Ann Oncol 2004; 15: 134­138.
44 Baz R, Li L, Kottke-Marchant K, Srkalovic G, McGowan B, Yiannaki E et al. The role of aspirin in the
24
prevention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple
myeloma. Mayo Clin Proc 2005; 80: 1568­1574.
45 Sidra G, Williams CD, Russell NH, Zaman S, Myers B, Byrne JL. Combination chemotherapy with
cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed
myeloma. Haematologica 2006; 91: 862­863.
46 Wu P, Davies FE, Horton C, Jenner MW, Krishnan B, Alvares CL et al. The combination of
cyclophosphomide, thalidomide and dexamethasone is an effective alternative to cyclophosphamide­
vincristine­doxorubicin­methylprednisolone as induction chemotherapy prior to autologous transplantation for
multiple myeloma: a case-matched analysis. Leuk Lymphoma 2006; 47: 2335­2338.
47 Dimopoulos MA, Hamilos G, Zomas A, Gika D, Efstathiou E, Grigoraki V et al. Pulsed cyclophosphamide,
thalidomide and dexamethasone: an oral regimen for previously treated patients with multiple myeloma.
Hematol J 2004; 5: 112­117.
48 Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, Polo-Zarzuela M, Sureda A, Barrenetxea C et al. The
oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in
relapsed/refractory multiple myeloma. Leukemia 2004; 18: 856­863.
49 Kropff MH, Lang N, Bisping G, Domine´ N, Innig G, Hentrich M et al. Hyperfractionated
cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary
refractory or relapsed multiple myeloma. Br J Haematol 2003; 122: 607­616.
50 Suvannasankha A, Fausel C, Juliar BE, Yiannoutsos CT, Fisher WB, Ansari RH et al. Final report of toxicity
and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with
relapsed or refractory multiple myeloma: a Hoosier Oncology Group Trial, HEM01-21. Oncologist 2007; 12:
99­106.
51 Barlogie B, Tricot G, Anaissie E, Shaughnessy J, Rasmussen E, van Rhee F et al. Thalidomide and
hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021­1030.
52 Zangari M, Siegel E, Barlogie B, Anaissie E, Saghafifar F, Fassas A et al. Thrombogenic activity of
doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002; 100: 1168­1171.
53 Lee C-K, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J et al. DTPACE: an effective, novel
combination chemotherapy with thalidomide for previously treated patients with myeloma. J Clin Oncol 2003;
21: 2732­2739.
54 Zonder JA. Thrombotic complications of myeloma therapy. Hematology Am Soc Hematol Educ Program
2006; 1: 348­355. 55 Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al.
Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed
multiple myeloma. Blood 2002; 100: 3063­3067.
56 Zangari M, Tricot G, Zeldis J, Eddlemon P, Saghafifar F, Barlogie B. Results of phase I study of CC-5013
for the treatment of multiple myeloma (MM) patients who relapse after high dose chemotherapy. Blood 2001;
98: 775a (abstract [3226]).
57 Zonder JA, Barlogie B, Durie BG, McCoy J, Crowley J, Hussein MA. Thrombotic complications in patients
with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin
prophylaxis. Blood 2006; 108: 403.
58 Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M et al. Phase III trial of
lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose Dexamethasone in newly
diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin
Oncol 2007; 25: 447s (abstract [8025]).
59 Dimopoulos MA, Spencer A, Attal M, Prince M, Harousseau J, Dmoszynska A et al. Study of lenalidomide
plus Dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of a
phase 3 study (MM-010). Blood 2005; 106: 6a (abstract [6]).
60 Weber D, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer E et al. Lenalidomide plus high-dose
dexamethasone provides improved overall survival compared to high-dose Dexamethasone alone for relapsed or
refractory multiple myeloma (MM): results of a North American phase III study (MM-009). J Clin Oncol 2006;
24: 427s (abstract [7521]).
61 Morgan GJ, Schey SA, Wu P, Srikanth M, Phekoo KJ, Jenner M et al. Lenalidomide (Revlimid), in
combination with cyclophosphamide and dexamethasone (RCD), is an effective and tolerated regimen for
myeloma patients. Br J Haematol 2007; 137: 268­269.
62 Richardson P, Schlossman R, Munshi N, Avigan D, Jagannath S, Alsina M et al. A phase 1 trial of
lenalidomide (REVLIMID(R)) with bortezomib (VELCADE(R)) in relapsed and refractory multiple myeloma.
Blood 2005; 106: 110a (abstract [365]).
63 Zangari M, Barlogie B, Thertulien R, Jacobson J, Eddleman P, Fink L et al. Thalidomide and deep vein
thrombosis in multiple myeloma: risk factors and effect on survival. Clin Lymphoma 2003; 4: 32­35.
25
64 Galli M, Elice F, Crippa C, Comotti B, Rodeghiero F, Barbui T. Recombinant human erythropoietin and the
risk of thrombosis in patients receiving thalidomide for multiple myeloma. Haematologica 2004; 89: 1141­
1142.
65 Knight R, DeLap RJ, Zeldis JB. Lenalidomide and venous thrombosis in multiple myeloma. N Engl J Med
2006; 354: 2079­2080.
66 Cohen AT, Alikhan R, Arcelus JI, Bergmann JF, Haas S, Merli GJ et al. Assessment of venous
thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94:
750­759.
67 Haas SK. Venous thromboembolic risk and its prevention in hospitalized medical patients. Semin Thromb
Hemost 2002; 28: 577­584.
68 Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA. Metaanlaysis: anticoagulant prophylaxis to
prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146:
278­288.
69 Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C et al. A comparison of enoxaparin
with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999;
341: 793­800.
70 Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ, PREVENT Medical
Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of
venous thromboembolism in acutely ill medical patients. Circulation 2004; 110: 874­879.
71 Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W et al. Efficacy and safety of
fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomized
placebo controlled trial. BMJ 2006; 332: 325­329.
72 Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D et al. Prevention
of venous thromboembolism in Thalidomide- and lenalidomide-associated thrombosis internal medicine with
unfractionated or low-molecular-weight heparins: a meta-analysis of randomized clinical trials. Thromb
Haemost 2000; 83: 14­19.
73 Francis CW. Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med 2007; 356:
1438­1444.
74 Geerts WH, Pineo GF, Heit JA, Berggvist D, Lassen MR, Colwell CW et al. Prevention of venous
thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126:
338­400.
75 Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: III.
reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and
medical patients. BMJ 1994; 308: 235­246.
76 Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism
Prevention (PEP) trial. Lancet 2000; 355: 1295­1302.
77 Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al. Prevention of venous
thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood
Coagul Fibrinolysis 2003; 12: 341­346.
78 Levine M, Hirsh J, Gent M, Arnold A, Warr D, Falanga A et al. Double-bind randomised trial of a very-low-
dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994; 343: 886­889.
79 Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin
sensitivity and risk of overanticoagulation in patients on long-term treatment. Blood 2000; 96: 1816­1819.
80 Wang M, Weber D, Delasalle K, Alexanian R. Thalidomide­ dexamethasone as primary therapy for
advanced multiple myeloma. Am J Hematol 2005; 79: 194­197.
81 Minnema MC, Breitkreutz I, Auwerda JJ, van der Holt B, Cremer FW, van Marion AM et al. Prevention of
venous thromboembolism with low molecular-weight heparin in patients with multiple myeloma treated with
thalidomide and chemotherapy. Leukemia 2004; 18: 2044­2046.
82 Offidani M, Corvetta L, Piersantelli MN, Visani G, Alesiani F, Brunori M et al. Thalidomide,
dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly
diagnosed multiple myeloma. Blood 2006; 108: 2159­2164.
83 Zangari M, Barlogie B, Anaissie E, Saghafifar F, Eddlemon P, Jacobson J et al. Deep vein thrombosis in
patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and
therapeutic anticoagulation. Br J Haematol 2004; 126: 715­721.
84 Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B et al. Combination therapy with
lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050­4053.
85 Palumbo A, Falco P, Corradini P, Falcone A, Di Raimondo F, Giuliani N et al. Melphalan, prednisone, and
Lenalidomide treatment for newly diagnosed myeloma. J Clin Oncol 2007; 25: 4459­4465.
26
86 Baz R, Walker E, Karam MA, Choueiri TK, Jawde RA, Bruening K et al. Lenalidomide and pegylated
liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy.
Ann Oncol 2006; 17: 1766­1771.
87 Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention for
atherothrombosis. N Engl J Med 2005; 353: 2373­2383.
88 US Food and Drug Administration Web site. Thalidomide package insert.
http://www.fda.gov/cder/foi/label/2006/021430s000, 020785s031lbl.pdf. Accessed September 6 2006.
89 US Food and Drug Administration Web site. Lenalidomide package insert.
http://www.fda.gov/cder/foi/label/2006/021880s001. pdf. Accessed September 6 2006.
90 Zangari M, Barlogie B, Lee CK, Tricot AE, Fassas A, Anaissie E et al. Protective effect of VELCADEs on
thalidomide-associated deep vein thrombosis (DVT). Blood 2004; 104: 13a (abstract [4914]).
91 Cestac P, Bagheri H, Lapeyre-Mestre M, Sie P, Fouladi A, Maupas E et al. Utilisation and safety of low
molecular weight heparins: prospective observational study in medical inpatients. Drug Saf 2003; 26: 197­207.
92 Nagge J, Crowther M, Hirsh J. Is impaired renal function a contraindication to the use of low-molecular-
weight heparin? Arch Intern Med 2002; 162: 2605­2609.
93 Thromboembolic Risk Factors (THRIFT) Consensus Group. Risk of and prophylaxis for venous
thromboembolism in hospital patients. BMJ 1992; 305: 567­574.
94 Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for
ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126
(Suppl 3): 483S­512S.
95 Lagerstedt CI, Olsson CB, Fagher BO, Oqvist BW, Albrechtsson U. Need for long term anticoagulant
treatment in patients with symptomatic calf-vein thrombosis. Lancet 1985; 2: 515­518.
96 Moser KM, Fedullo PF, LittleJohn JK, Crawford R. Frequent asymptomatic pulmonary embolism in patients
with deep venous thrombosis. JAMA 1994; 271: 223­225.
97 Bozlar U, Gaughen JR, Nambiar AP, Hagspiel KD. Imaging diagnosis of acute pulmonary embolism. Expert
Rev Cardiovasc Ther 2007; 5: 519­529.
98 Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to
clinical and thrombophilic risk factors: prospective cohort study. Lancet 2003; 362: 523­526.
99 Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Martin Prins MB et al. Low-molecular-weight
heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N
Engl J Med 2003; 349: 146­153.
###

Document Outline