OCTOBER 2004

Pulmonary embolism of polymethyl methacrylate during percutaneous vertebroplasty and kyphoplasty.
AJR Am J Roentgenol. 2004 Oct;183(4):1097-102.
Choe DH, Marom EM, Ahrar K, Truong MT, Madewell JE.
This study reviewed the findings of CXR taken after percutaneous vertebroplasty procedures in 64 patients. Pulmonary emboli of cement in lungs were noted in 3 of 65 (4.6%) vertebroplasty or kyphoplasty. The findings at the CXR were multiple radiodense opacities with a tubular and branching shape. All patients with cement pulmonary embolism to lungs were asymptomatic. Pulmonary embolism of cement was not correlated with the type of procedure performed, kyphoplasty vs vertebroplasty.

A technique to circumvent subcutaneous cement tracts during percutaneous vertebroplasty.
AJNR Am J Neuroradiol. 2004 Oct;25(9):1595-6.
Kaufmann TJ, Wald JT, Kallmes DF.

Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma.
Br J Haematol. 2004 Oct;127(2):159-64.
Hernández JM, García-Sanz R, Golvano E, Bladé J, Fernandez-Calvo J, Trujillo J, Soler JA, Gardella S, Carbonell F, Mateo G, San Miguel JF.
This is a randomized trial comparing MP (melphalan + prednisone, the standard arm) vs MD (melphalan + dexamethasone) in 201 myeloma patients 70 years old or older.
  - Response rates after 6 cycles were similar: 67.9% with MP and 64.5% with MD
  - Response rates after 12 cycles were similar: 49.4% with MP and 46.1% with MD
  - Rates of complete response after 12 cycles were higher in the MD arm: 9.1% with MP and 22.4% with MD (p <0.05)
  - Median event-free survival was similar: 15.9 months with MP and 23.3 months with MD
  - Median overall survival was similar: 29.4 months with MP and 27.2 months with MD (p= 0.63)
  - Toxicity was higher in the MD group, specifically the non-hematological toxicity.
At the time of the study, MP remained the standard treatment for myeloma patients not eligible for stem cell transplantation.

A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma.
Br J Haematol. 2004 Oct;127(2):165-72.
Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC.
In this phase II trail, 54 patients with relapsed/refractory myeloma were randomized to receive bortezomib 1.0 or 1.3 mg/m2 IV, for a maximum of 8 cycles. Patient received dexamethasone in case of no disease response. Results:
  - Response rate: 37% with 1.0 mg/m2 and 50% with 1.3 mg/m2
Most common grade III toxicities:
  - Thrombocytopenia (24%), neutropenia (17%)
  - Peripheral neuropathy (9%)

Tumour lysis syndrome in multiple myeloma after bortezomib (VELCADE) administration.
J Cancer Res Clin Oncol. 2004 Oct;130(10):623-5.
Terpos E, Politou M, Rahemtulla A
.

Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma.
Biol Blood Marrow Transplant. 2004 Oct;10(10):698-708.
Kröger N, Perez-Simon JA, Myint H, Klingemann H, Shimoni A, Nagler A, Martino R, Alegre A, Tomas JF, Schwerdtfeger R, Kiehl M, Fauser A, Sayer HG, Leon A, Beyer J, Zabelina T, Ayuk F, San Miguel JF, Brand R, Zander AR.
This study evaluated outcomes of 120 myeloma patients treated with melphalan/fludarabine-based allogeneic SCT. Results:
  - Treatment-related mortality at 1 year: 18%
  - CR 49%, PR 38%
  - With related donors (34 patients): 2-year EFS 60%, 2-year OS 75%
  - With MUD (12 patients): 2-year EFS 81%, 2-year OS 92%

 

NOVEMBER 2004

PI3-K/AKT/FKHR and MAPK signaling cascades are redundantly stimulated by a variety of cytokines and contribute independently to proliferation and survival of multiple myeloma cells.
Leukemia. 2004 Nov;18(11):1883-90.
Lentzsch S, Chatterjee M, Gries M, Bommert K, Gollasch H, Dörken B, Bargou RC.
Many different factors activate the growth and survival of MM cells. IL-6 and several bone marrow derived cytokines such as LIF, VEGF, bFGF, MIP-1alpha, SDF-1alpha, IL-1beta, SCF and IL-3 activated the MAPK pathway and induced proliferation of MM cells in vitro. These cytokines independently phosphorylated the PI3-K/AKT pathway and supported survival of primary human MM cells.

Multiple myeloma involving central nervous system: high frequency of chromosome 17p13.1 (p53) deletions.
Br J Haematol. 2004 Nov;127(3):280-4.
Chang H, Sloan S, Li D, Keith Stewart A.
These authors describe 9 patients with CNS MM. At FISH, 8 cases had p53 deletion and 4 had 13q deletion.

An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma.
Br J Cancer. 2004 Nov 29;91(11):1873-9.
Hus I, Dmoszynska A, Manko J, Hus M, Jawniak D, Soroka-Wojtaszko M, Hellmann A, Ciepluch H, Skotnicki A, Wolska-Smolen T, Sulek K, Robak T, Konopka L, Kloczko J.

Treatment of relapsed/refractory multiple myeloma with thalidomide-based regimens: identification of prognostic factors.
Leuk Lymphoma. 2004 Nov;45(11):2275-9.
Anagnostopoulos A, Gika D, Hamilos G, Zervas K, Zomas A, Pouli A, Zorzou M, Kastritis E, Anagnostopoulos N, Tassidou A, Anagnostou D, Dimopoulos MA.

Evaluation of gemcitabine in relapsed or refractory multiple myeloma.
Haematologica. 2004 Nov;89(11):ELT15.
Leleu X, Troncy J, Bouafia F, Michallet M, Facon T, Dumontet C.

Human multiple myeloma cells express peroxisome proliferator-activated receptor gamma and undergo apoptosis upon exposure to PPARgamma ligands.
Clin Immunol. 2004 Nov;113(2):203-13.
Ray DM, Bernstein SH, Phipps RP.

 

DECEMBER 2004

Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome.
Bone Marrow Transplant. 2004 Dec;34(12):1057-65.
Zeiser R, Deschler B, Bertz H, Finke J, Engelhardt M.
This study reviewed data of 78 myeloma patients treated with stem cell transplantation (autologous in 53 patients, and allogeneic in 25 patients), and it compared outcomes of 14 patients with "extramedullary relapse" vs 64 patients with "bone marrow relapse". The sites of extramedullary relapse were lungs, soft tissues, pericardium, skin, and CNS. OS and PFS survival in the group with extramedullary relapse were similar to those of the group with bone marrow relapse. Treatment with DLIs induced disease remission in 5 of 9 (56%) patients with bone marrow relapse, and in 3 of 4 (75%) patients with extramedullary relapse.

Results of a multicenter randomized phase II trial of thalidomide and prednisone maintenance therapy for multiple myeloma after autologous stem cell transplant.
Clin Cancer Res. 2004 Dec 15;10(24):8170-6.
Stewart AK, Chen CI, Howson-Jan K, White D, Roy J, Kovacs MJ, Shustik C, Sadura A, Shepherd L, Ding K, Meyer RM, Belch AR.
This is a randomized phase II trial using thalidomide 200 or 400 mg PO qhs + prednisone 50 mg PO qod as post-transplant maintenance in 77 patients with multiple myeloma. After a median follow-up of 37 months, discontinuation rate for thalidomide was 88% (24% with 200 mg and 59% with 400 mg), even allowing dose reductions. Dose reduction for prednisone were needed in 72% of patients. Median progression-free survival was 32.3 months from the time of transplant, and 42.2 months from the time of diagnosis.

In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model.
Blood. 2004 Dec 15;104(13):4181-7.
Frost P, Moatamed F, Hoang B, Shi Y, Gera J, Yan H, Frost P, Gibbons J, Lichtenstein A.

Abnormal cytogenetics and significant bone marrow plasmacytosis are predictive of early progression and short survival in patients with low tumor mass asymptomatic multiple myeloma.
Leuk Lymphoma. 2004 Dec;45(12):2481-4.
Depil S, Leleu X, Micol JB, Berthon C, Laď JL, Bauters F, Quesnel B, Facon T.

 

 


Giampaolo Talamo, M.D.