International Myeloma Foundation
2650 Riverside Drive, Suite 206
North Hollywood, CA 9607-342
Hotline (USA & Canada): (800) 452 CURE (2873)
Tel: (88) 487-7455
Fax: (88) 487-7454
Email: TheIMF@myeloma.org
Website: www.myeloma.org
Dedicated to improving the quality of life
of myeloma patients while working
towards prevention and a cure.
2007
Published by the International Myeloma Foundation
© 2007, International Myeloma Foundation
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4
7.
· Major P, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy:
a pooled analysis of two randomised, controlled clinical trials. Journal of Clinical Oncology 2001; 19, 558-67.
· McCloskey EV, et al. A randomised trial of the effect of clodronate on skeletal morbidity in multiple myeloma.
. 12.
Br J Haematol 1998; 100: 317-25.
· Berenson J, et al. Long-term pamidronate treatment of advanced multiple myeloma reduces skeletal events.
(, Doxil®)
Journal of Clinical Oncology 1998; 16: 593-602.
(CNTO 328, -IL-6 Avastin®,
· Mundy, GR, Yoneda T. Bisphosphonates as anticancer drugs. New England Journal of Medicine 1998;
-VEGF ), [,
339: 398-400.
(ATO), ZIO-101 ( ),
· Berenson J, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple
myeloma. New England Journal of Medicine 1996; 334: 488-493.
], HSP , , .
· Bataille R, et al. Mechanism of bone destruction in multiple myeloma. The importance of an unbalanced process
,
in determining the severity of lytic bone disease. Journal of Clinical Oncology 1989; 7: 1909.
IMF [800-452-2873 , +1-818-
· Durie BGM, Salmon SE, Mundy GR. Relation to osteoclast activating factor production to extent of bone disease
487-7455 ] (www.myeloma.org),
in multiple myeloma. Br J Haematol 1981; 47: 21-26.
.
:
Myeloma Matrix© .
· Dewald GW, Therneau T, et al. Relationship of patient survival and chromosome anomalies detected in meta-
, ,
phase and/or interphase cells at diagnosis of myeloma. Blood. 2005;106(10):3553-8.
. (2005)
· Jaksic W, Trudel S, Chang H, et al. Clinical outcomes in t(4,14) multiple myeloma: a chemotherapy sensitive
disease characterized by rapid relapse and alkylating agent resistance. J Clin Oncol 2005;23(28):7069-73.
, ,
· Konigsberg R, Zojer N, Ackermann J, et al. Predictive role of interphase cytogenetics for survival of patients with
ASH, ASCO,
multiple myeloma. Journal of Clinical Oncology. 2000; 18: 804-812.
EHA IMWG ( , IMF
· Durie BGM, et al. Cytogenetic abnormalities in multiple myeloma. Epidemiology and Biology of Multiple
www.myeloma.org).
Myeloma. New York: Springer-Verlag, 1991: 137-41.
MGUS :
· Kyle RA, Therneau TM, Rajkumar SV, Offord JR. A long-term study of prognosis in mono-clonal gammopathy of
undetermined significance. New England Journal of Medicine. 2002; 346: 564-569.
· Weber DM, et al. Prognostic features of asymptomatic multiple myeloma. British Journal of Haematology. 1997;
97: 810-4.
:
· Kyle RA, Greipp PR. Smoldering multiple myeloma. New England Journal of Medicine. 1980; 302: 1347-49.
· Gahrton G, Durie BGM, Samson DM. Multiple Myeloma and Related Disorders. Oxford University Press 2004
ISBN: 0-89603-706-1.
:
· Berenson James R. Biology and Management of Multiple Myeloma. Humana Press. 2004 ISBN 0-89603-706-1.
· Greipp PR , Durie, BGM, et al. International Staging System for multiple myeloma. J Clin Oncol.
· Mehta J, Singhal S, eds. Myeloma, Dunitz M. Taylor and Francis Group, 2002: ISBN 1-901865-50-9.
2005:23(15):3412-20.
· Bataille R, Harousseau JL. Multiple myeloma. New England Journal of Medicine. 1997; 336: 1657-1664.
· Gahrton G, Durie BGM, et al. Multiple Myeloma and Related Disorders, The role of imaging in myeloma. Arnold
2004. 10:155-63.
:
· Jacobson J, Hussein M, Barlogie B, Durie BGM, Crowley J. A new staging system for multiple myeloma patients
· Kyle RA. History of multiple myeloma. In: Neoplastic Diseases of the Blood, 3rd edition. (Wiernik PH, Canellos
based on the Southwest Oncology Group (SWOG) experience. Br J Haematol 2003; 122: 441-450
GP, Kyle RA, Schiffer CA, eds). New York: Churchill Livingstone, 1996.
· Greipp RR, San Miguel JF, Fonesca R, Avet-Loiseau H, Jacobson JL, Durie BGM. Development of an International
· Kyle RA. History of multiple myeloma. In: Neoplastic Diseases of the Blood, 2nd edition.(Wiernik PH, Canellos
Prognostic Index (IPI) for myeloma: report of the International Myeloma Working Group. Haematol J 2003; 4
GP, Kyle RA, Schiffer CA, eds). New York: Churchill Livingstone, 1991: 325-32.
(suppl.1): p 7.1, S43-S44.
:
· Facon T, et al. Chromosome 13 abnormalities identified by FISH analysis and serum ß²- microglobulin produce a
· American Cancer Society Facts & Figures 2007.
powerful myeloma staging system for patients receiving high-dose therapy. Blood 2001; 97: 1566-71.
· Jemal A, Thomas A, Murray T, Thun M. Cancer statistics 2002. CA Cancer J Clin 2002; 52: 23-47.
· Zojer N, et al. Deletion of 13q14 remains an independent prognostic variable in multiple myeloma despite its
· Schwartz GG. Multiple myeloma: clusters, clues, and dioxins. Cancer Epidemiol Biomarkers Prev. 1997;
frequent detection by interphase fluorescence in situ hybridization. Blood 2001; 95: 1925-30.
6: 49-56.
· Bataille R, Boccadoro M, Klein B, et al. C-reactive protein and ß2-microglobulin produce a simple and powerful
· Schottenfeld D, Fraumeni JF Jr. (eds). Cancer Epidemiology and Prevention, 2nd edn. New York: Oxford
myeloma staging system. Blood 1992; 80: 733-7.
University Press; 1996: 946-970.
· Durie BGM, Stock-Novack D, Salmon SE, et al. Prognostic value of pre-treatment serum ß² microglobulin in
· Herrington LJ, Weiss NS, Olshan AF. The epidemiology of myeloma. In: Myeloma Biology and Management
myeloma: a Southwest Oncology Group study. Blood 1990; 75: 823-30.
(Malpas JS, Bergsagel DE, Kyle RA eds.). Oxford, England, Oxford University Press: 1995: 127-168.
· Greipp PR, et al. Value of ß²-microglobulin level and plasma cell labeling indices as prognostic factors in patients
with newly diagnosed myeloma. Blood 1988; 72: 219-23.
:
· Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S et al. Collapsing focal segmental glomerulo-
· Durie BGM, Salmon SE. A clinical staging system for multiple myeloma. Cancer 1975; 36: 842-54.
sclerosis following treatment with high-dose pamidronate. J AM Soc Nephrol 2001; 12: 1164-1172.
:
· Rosen LS, Gordon D, Antonio BS, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metasta-
· Durie BGM, Jacobson J, Barlogie B, Crowley J. Magnitude of Response with Myeloma Frontline Therapy Does
ses in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase II, double blind, compara-
Not Predict Outcome: Importance of Time to Progression in Southwest Oncology Group Chemotherapy Trials.
tive trial. Cancer J 2001; 7: 377-387.
Journal of Clinical Oncology 2004; 22:1857-1863.
42
43
· Durie BGM, Kyle RA, Belch A, Bensinger et al. Myeloma management guidelines, a consensus report from the
· Fernaud JP, Ravaud P, Chevert S, et al. High-dose therapy and autologous peripheral blood stem cell transplanta-
Scienctific Advisors of the International Myeloma Foundation. The Hematology Journal 2003; 4:379-398.
tion in multiple myeloma: upfront or rescue treatment? Results of a multicenter sequential randomized clinical
· Kumar A, Loughran MA, Durie BGM, et al. Management of multiple myeloma: a systematic review and critical
trail. Blood 1998; 92: 3131-3136.
appraisal of published studies. Lancet Oncology 2003; 4: 293-304.
· Attal M, Harousseau JL, Stoppa A-M, et al. A prospective, randomized trial of autologous bone marrow transplan-
· Myeloma Trialists' Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as
tation and chemotherapy in multiple myeloma. New England Journal of Medicine 1996; 335: 91-97.
treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. Journal of Clinical
· Gore ME, Viner C, Meldrum M. Intensive treatment of multiple myeloma and criteria for complete remission.
Oncology 1998; 16: 3832-42.
Lancet 1989; 14:879-882.
· Alexanian R, et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887-90.
· McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet 1983;
· MacLennan ICM, et al, for the MRC Working Party on Leukaemia in Adults. Combined chemotherapy with ABCM
2: 822-824.
versus melphalan for treatment of myelomatosis. Lancet 1992; 339: 200-5.
:
· Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for myeloma. American Journal of
· Maloney DG, Sahebi F, Stockerl-Goldstein KE, et al. Combining an allogeneic graft-vs.-myeloma effect with high-
Hematology 1990; 33: 86-9.
dose autologous stem cell rescue in the treatment of multiple myeloma [abstract]. Blood 2001; 98 (11. pt 1):
· Alexanian R, et al. Treatment for multiple myeloma: combination chemotherapy with different melphalan dose
435a Abstract 2063.
regimens. Journal of the American Medical Association 1969; 208: 1680-5.
· Gahrton G, et al. Progress in allogeneic hematopoietic stem cell transplantation for multiple myeloma. Bone
:
Marrow Transplant 2000; 25 (suppl. 1): S54.
· Richardson P, Barlogie B, Berenson J, et al. A phase II multicenter study of the protease inhibitor bortezomib
· Bensinger WI, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: an analy-
(VELCADE® formerly PS-341) in multiple myeloma patients (pts) with relapsed/refractory disease. New England
sis of risk factors on outcome. Blood 1996; 88: 2787-2793.
Journal of Medicine 2003; 348:2609-2617.
· Bensinger WI, Demirer, T, Buckner CD, et al. Syngeneic marrow transplantation in patients with multiple
· Alexanian R, Dimopoulus M. The treatment of multiple myeloma. New England Journal of Medicine 1994; 330:
myeloma. Bone Marrow Transplant 1996; 18: 527-31.
484-9.
· Gahrton G,. et al. Allogeneic bone marrow transplantation in multiple myeloma. Br J Haematol 1996;
· Buzaid AC, Durie BGM. Management of refractory myeloma -a review. Journal of Clinical Oncology 1988;
92:251-254.
6: 889-905.
· Durie BGM, Gale RP, Horowitz MM. Allogeneic and twin transplants for multiple myeloma: an IBMTR analysis.
:
Multiple myeloma. From biology to therapy. Current concepts. INSERM, Mulhouse, 24-26 October, 1994
· Hideshima T, Bergsagel PL, Kuehl WM et al. Advances in biology of multiple myeloma: clinical applications.
(abstract).
Blood 2004; 104:607-618.
· Samson D. The current position of allogeneic and autologous BMT in multiple myeloma. Leukemia and
· Bladé J, Estve J. Viewpoint on the impact of interferon in the treatment of multiple myeloma: benefit for a small
Lymphoma 1992; 7: 33.
proportion of patients? Med Oncology 2000; 77-84.
:
· Mandelli F, et al. Maintenance treatment with alpha 2b recombinant interferon significantly improves response
· Oken M, Pomeroy C, Weisdorf D, et al. Prophylactic antibiotics for the prevention of early infection in multiple
and survival duration in multiple myeloma patients responding to conventional induction chemotherapy. Results
myeloma. American Journal of Medicine. 1996; 100: 624-28.
of an Italian randomized study. New England Journal of Medicine 1990; 322: 1430.
· Osterborg A, Boogaerts MA, Cimino R, et al. Recombinant human erythropoietin in trans-fusion-dependent
· Ludwig H, Fritz E, Kotzmann H, et al. Erythropoietin treatment of anemia associated with multiple myeloma.
anemic patients with multiple myeloma and non-Hodgkin's lymphoma-a randomized multicenter study. Blood
New England Journal of Medicine 1990; 322: 1693-9.
1996; 87:2675-2682.
· Musto P, et al. Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory
· Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin
multiple myeloma: role of cytokines and monitoring of erythropoiesis. European Journal of Haematology 1997;
Hematology. 1995; 32: 45-59.
58: 314-19.
· Chapel HM, Lee M, Hargreaves R, et al. Randomized trial of intravenous immunoglobulin as prophylaxis against
:
infection in plateau-phase multiple myeloma. Lancet. 1994; 343: 1059-1063.
· Cavo M, Zamagni E, Tosi P, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicin-
· Johnson WJ, Kyle RA, Pineda AA, et al. Treatment of renal failure associated with multiple myeloma.
dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma.
Plasmapheresis, hemodialysis and chemotherapy. Arch Internal Medicine. 1990; 150: 863-69.
Blood. 2005;106:35-9.
· Ludwig H, Fritz E, Kotsmann H, et al. Erythropoietin treatment of anemia associated with multiple myeloma. New
· Bensinger WI. The Role of Hematopoietic Stem Cell Transplantation in the Treatment of Multiple Myeloma.
England Journal of Medicine 1990; 233:1693-1699.
Journal of National Comprehensive Cancer Network 2004; 2: 371-378.
:
· Dispenzieri A, Kyle RA, Lacy MQ, et al. Superior survival in primary systemic amyloidosis patients undergoing
Blood Journal
peripheral blood stem cell transplantation: a case-control study. Blood 2004; 103: 3960-3963.
· Harousseau J-L, Marit G, Caillot D, et al. VELCADE/dexamethasone vs VAD as induction treatment prior to ASCT
· Desikan KR, Barlogie B, Sawyer J, et al. Results of high-dose therapy for 100 patients with multiple myeloma:
in newly diagnosed multiple myeloma: A preliminary analysis of the IFM 2005-01 randomized multicenter phase
durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 2000;
3 trial. Blood 2006; 108: abstract #56.
95: 4008-4010.
· Orlowski RZ, Peterson BL, Sanford B, et al. Bortezomib and pegylated liposomal doxorubicin as induction
· Martinelli G, Terragna C, Zamagni E, et al. Molecular remission after allogeneic or autologous transplantation of
therapy for adult patients with symptomatic multiple myeloma: Cancer and Leukemia Group B study 10301.
hematopoietic stem cells for multiple myeloma. Journal of Clinical Oncology 2000; 18: 2273-81.
Blood 2006; 108: abstract #797.
· Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple
· Orlowski RZ, Zhuang SH, Parekh T, et al. The combination of pegylated liposomal doxorubicin and bortezomib
myeloma. Blood 1999; 93: 55-65.
significantly improves time to progression of patients with relapsed/refractory multiple myeloma compared
· Cunningham D, et al. A randomized trial of maintenance interferon following high-dose chemotherapy in mul-
with bortezomib alone: results from a planned interim analysis of a randomized phase III study. Blood 2006;
tiple myeloma: long-term follow-up results. Br J Haematol 1998; 102: 495-502.
108: abstract #404.
· Mehta J, Powles RL. Autologous blood and marrow transplantation. In: Leukaemia and Associated Diseases.
· Palumbo A, Ambrosini MT, Benevolo G, et al. Combination of bortezomib, melphalan, prednisone and tha-
(Whittaker JA, Holmes JA, eds). Oxford: Blackwell Science, 1998; 455-81.
lidomide (VMPT) for relapsed multiple myeloma: results of a phase I/II clinical trial. Blood 2006; 108: abstract
#407.
44
45
· Palumbo A, Flaco P, Falcone A, et al. Oral Revlimid® plus melphalan and prednisone (R-MP) for newly diagnosed
multiple myeloma: results of a multicenter phase I/II study. Blood 2006; 108: abstract #800.
· Rajkumar SV, Hussein M, Catalano J, et al. A multicenter, randomized, double-blind, placebo-controlled study
of thalidomide plus dexamethasone versus dexamethasone alone as initial therapy for newly diagnosed multiple
myeloma (MM 003). Blood 2006; 108: abstract #795.
· Rajkumar SV, Jacobus S, Callender N, et al. A randomized phase III trial of lenalidomide plus high-dose dexa-
methasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a
trial coordinated by the Eastern Cooperative Oncology Group. Blood 2006; 108: abstract #799.
· Richardson PG, Jagannath S, Avigen DE, et al. Lenalidomide plus bortezomib (Rev-VEl) in relapsed and/or refrac-
tory multiple myeloma (MM): final results of a multicenter phase 1 trial. Blood 2006; 108: abstract #405.
· Palumbo A, Bertola A, et. al. A prospective randomized trial of oral melphalan, prednisone, thalidomide (MPT) vs.
oral melphalan, prednisone (MP): an interim analysis. [abstract] Blood. 2005;104(11):63a. Abstract 207.
· Rajkumar SV. Multiple myeloma: the death of VAD as initial therapy. Blood. 2005;106:2.
· Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with CC-5013 (lenalidomide; Revlimid) plus
dexamethasone (Rev/Dex) for newly diagnosed myeloma (MM) [abstract]. Blood. 2004;104:98a. Abstract 331.
· Barlogie B, Desikan KR, Eddelman P, 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;
32: 45-59.
· Hussein MA, Mason J, Ravandi F, Rifkin R. A phase II clinical study of arsenic trioxide (ATO) in patients with
relapsed or refractory multiple myeloma; a preliminary report. Blood 2001; 98: 378a.
· Richardson P, Schlossman RL, Hideshima F, et al. A Phase I study of oral CC5013, an immunomodulatory thalido-
mide (Thal) derivative, in patients with relapsed and refractory multiple myeloma. Blood 2001; 98: 775a.
· Thomas D, Cortes J, O'Brian SM, et al. R115777, a farnesyl transferase inhibitor (FTI), has significant anti-leukae-
mia activity in patients with chronic myeloid leukaemia (CML). Blood 2001; 98: 727a.
British Journal of haematology
· Berenson JR, Boccia R, Sigel D, et al. Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid com-
bination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicenter, phase II,
single-arm study. Br J Haem 2006; 135:174-183.
· Jagannath S, Durie BGM, et al. Bortezomib therapy alone and in combination with dexamethasone for previously
untreated symptomatic multiple myeloma. Br J Haematol. 2005;129:776-83.
· Oakervee HE, Popat R., et al. PAD combination therapy (PS341/bortezomib, doxorubicin and dexamethasone) for
previously untreated patients with multiple myeloma. Br J Haematol. 2005;129:755-62.
Journal of CliniCal onCology
· Barlogie B, Anaissie E, Bolejack V, et al. High CR and near-CR rates with bortezomib incorporated into up-front
therapy of multiple myeloma with tandem transplants. J Clin Oncol 2006; 24: abstract #7519.
· Niesvizsky R, Jayabalan DS, Furst JR, et al. Clarithromycin, lenalidomide and dexamethasone combination
therapy as primary treatment of multiple myeloma. J Clin Oncol 2006; 24: abstract #7545.
· Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility of peripheral neu-
ropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 2006;24:3113-3120.
· Richardson PG, Chanan-Khan A, Schlossman R, et al. Single-agent bortezomib in previously untreated, symptom-
atic multiple myeloma (MM): results of a phase 2 multicenter study. J Clin Oncol 2006; 24: abstract #7504.
lanCet onCology
· Bruno B, Rotta M, Giaccone L, et al. New drugs for treatment of multiple myeloma Lancet Oncology 2004;
5(July) 1-16.
mayo CliniC
· Rajkumar SV and Kyle R. Multiple Myeloma: Diagnosis and Treatment. Mayo Clinic Proc. 2005;80(10):1371-
1382.
new england Journal of mediCine
· Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple
myeloma. New Engl J Med 2005;352:2487-2498.
ameriCan soCiety of CliniCal onCology
· Richardson PG, Barlogie B, Berenson J, et al. Phase II study of the proteasome inhibitor PS341 in multiple
myeloma patients with relapsed/refractory disease. Proc Am Soc Clin Oncol 2002; 21: 11a.
46