Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis.
Leukemia. 2007 Jan;21(1):143-50.
Gutiérrez NC, Castellanos MV, Martín ML, Mateos MV, Hernández JM, Fernández M, Carrera D, Rosińol L, Ribera JM, Ojanguren JM, Palomera L, Gardella S, Escoda L, Hernández-Boluda JC, Bello JL, de la Rubia J, Lahuerta JJ, San Miguel JF; GEM/PETHEMA Spanish Group.
260 myeloma patients were analyzed by FISH. Patients with t(4;14), Rb or p53 deletions had a shorter overall survival than patients without these abnormalities, but patients with Rb deletions without other abnormalities had a similar outcome to patients with negative FISH (46 vs 54 months, p= 0.3).

Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma.
Haematologica. 2007 Jan;92(1):56-65.
Agnelli L, Bicciato S, Fabris S, Baldini L, Morabito F, Intini D, Verdelli D, Callegaro A, Bertoni F, Lambertenghi-Deliliers G, Lombardi L, Neri A.
These authors analyzed the transcriptional features of monosomy 13 in MM. Plasma cells from 80 newly diagnosed MM patients were characterized by cytogenetics, FISH, and gene expression profiling. 67 differentially expressed genes in patients with and without -13 were identified. Functional analyses of selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation.

A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7.
Br J Haematol. 2007 Jan;136(2):203-11.
Shustik C, Belch A, Robinson S, Rubin SH, Dolan SP, Kovacs MJ, Grewal KS, Walde D, Barr R, Wilson J, Gill K, Vickars L, Rudinskas L, Sicheri DA, Wilson K, Djurfeldt M, Shepherd LE, Ding K, Meyer RM.
466 older patients were randomized to either MP (melphalan + prednisone) or M-Dex (melphalan + dexamethasone) as induction therapy, then treated with dexamethasone or observation as maintenance therapy. Dexamethasone did not improve outcomes in induction therapy, when combined with melphalan: MP and M-Dex produced similar outcomes, in terms of median progression-free survival (1.8 vs 1.9 years, p= 0.2] and median overall survival (2.5 vs 2.7 years, p = 0.3). Maintenance therapy with dexamethasone improved progression-free survival but not overall survival: the group treated with maintenance dexamethasone had better PFS (2.8 vs 2.1 years, p= 0.0002), but similar median OS (4.1 vs 3.8 years, p= 0.4).

PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells.
Leukemia. 2007 Jan;21(1):187-90.
Otsuyama KI, Ma Z, Abroun S, Amin J, Shamsasenjan K, Asaoku H, Kawano MM.

Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains.
Haematologica. 2007 Jan;92(1):143-4.
Dawson MA, Patil S, Spencer A.



Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma.
Am J Clin Pathol. 2007 Feb;127(2):176-81.
Seegmiller AC, Xu Y, McKenna RW, Karandikar NJ.

Based on morphologic features, it may be difficult to differentiate between plasmacytomas and non-Hodgkin lymphomas with plasmacytic differentiation. This study shows that immunophenotyping by flow cytometry can differentiate between these two pathologic entities: plasma cells in non-Hodgkin lymphoma are usually CD19+, CD45+, CD56-, and sIg+, while plasmacytomas usually have the reverse phenotype. CD19 and CD56 are the most useful markers for the differential diagnosis (plasma cells in solitary plasmacytoma of bone and multiple myeloma are usually CD19- and CD56+). Based on immunophenotyping, some cases of extramedullary plasmacytomas can be reclassified as MZL or other B-cell NHL with plasmacytic differentiation.

Monitoring serum free light chains in patients with multiple myeloma who achieved negative immunofixation after allogeneic stem cell transplantation.
Haematologica. 2007 Feb;92(2):275-6.
Mösbauer U, Ayuk F, Schieder H, Lioznov M, Zander AR, Kröger N.
In 26 myeloma patients treated with allogeneic stem cell transplant, serum free light chains anticipated the achievement of remission (they decreased at a median of 128 days before IFE became negative), and they anticipated disease relapse (a 25% increase of FLC was observed at a median of 98 days before IFE became positive).

Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma.
Am J Clin Pathol. 2007 Feb;127(2):176-81.
Seegmiller AC, Xu Y, McKenna RW, Karandikar NJ.
It is often difficult to differentiate between plasmacytoma/myeloma and non-Hodgkin lymphomas with marked plasmacytic differentiation. This study compares the immunophenotypic differentiation of 41 cases of B-cell NHL with the findings in plasma cell myeloma, and it showed that plasma cells in NHL are more likely to be negative for CD56 and positive for surface immunoglobulin, CD19, and CD45 than myeloma cells. Myeloma and NHL with plasmacytic differentiation can be reliably distinguished based on CD19 and CD56 expression. Since extramedullary plasmacytoma shows a lymphoma-like phenotype, the authors believe that at least some cases of primary extramedullary plasmacytomas may in fact be NHL with marked plasmacytic differentiation.


MARCH 2007

A comparison of allografting with autografting for newly diagnosed myeloma.
N Engl J Med. 2007 Mar 15;356(11):1110-20.
Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omedč P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M.
This is a trial of 162 patients with newly diagnosed multiple myeloma, age 65 or younger. The authors compared tandem autologous-autologous SCT (82 patients) vs tandem autologous-allogeneic SCT (80 patients). Patients without an HLA-identical sibling received two autologous SCT using melphalan 100-200 mg/m2, whereas patients with an HLA-identical sibling underwent a second SCT with a nonmyeloablative allogeneic protocol using TBI 200 cGy (19% received DLI). Median follow-up was 45 months (range, 21-90). Results:
  - Treatment-related mortality was similar
  - Disease-related mortality was 43% in the auto-auto group and 7% in the auto-allo group (p <0.001)
  - Median OS was 54 months in the auto-auto group and 80 months in the auto-allo group (p= 0.01)
  - Median EFS was 29 months in the auto-auto group and 35 months in the auto-allo group (p= 0.02)
The authors concluded that in patients with newly diagnosed myeloma, outcomes of tandem autologous-allogeneic SCT are superior to those of tandem autologous-autologous SCT. Some experts have criticized this conclusion, because of the relatively poor outcome of the auto-auto group in this trial. Other series of tandem autologous transplants have reported better median overall survival.

Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis.
J Immunol. 2007 Mar 1;178(5):3307-15.
Condomines M, Hose D, Raynaud P, Hundemer M, De Vos J, Baudard M, Moehler T, Pantesco V, Moos M, Schved JF, Rossi JF, Rčme T, Goldschmidt H, Klein B.

Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo.
Blood. 2007 Mar 1;109(5):2106-11.
Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr.
This study tested the effect of anti-DKK1 therapy on bone metabolism and tumor growth in SCID-rab mice. The bone mineral density (BMD) of implanted myelomatous bone in mice treated with DKK1-neutralizing antibodies increased. Histology showed an increased numbers of osteoblasts and reduced number of osteoclasts. At the same time, the MM growth was inhibited.

Recombinant human erythropoietin is associated with increased overall survival in patients with multiple myeloma.
Acta Haematol. 2007 Mar;117(3):162-7.
Baz R, Walker E, Choueiri TK, Abou Jawde R, Brand C, McGowan B, Yiannaki E, Andresen S, Hussein MA.
This study reviews outcomes of 257 patients with multiple myeloma. 127 of them received EPO for at least 1 month, and 130 did not. After adjusting for several variables, the use of EPO was found to be associated with improved overall survival (hazard ratio = 0.6) in patients with SWOG stages II, III and IV.

Long-term follow-up of gene-marked CD34+ cells after autologous stem cell transplantation for multiple myeloma.
Cancer Gene Ther. 2007 Mar;14(3):227-32.
Alici E, Björkstrand B, Treschow A, Aints A, Smith CI, Gahrton G, Dilber MS.
This study indicates that relapse of myeloma after autologous transplant is likely not related to the presence of contaminating tumor cells in the apheresis products. The authors used gene marking with integrated retroviral vectors in autologous CD34+ enriched BM or peripheral blood cell grafts from 8 myeloma patients. The transgene product was detected for up to 5 years post-transplant. Interestingly, there were no marked myeloma cells in patients with relapsed myeloma, supporting the hypothesis that relapse was related to the inability of high-dose chemotherapy to eradicate the original myeloma clone.

Thrombosis in multiple myeloma.
Expert Rev Anticancer Ther. 2007 Mar;7(3):307-15.
Zangari M, Elice F, Fink L, Tricot G.



Giampaolo Talamo, MD