Insulin-like growth factor I induces migration and invasion of human multiple myeloma cells.
Blood. 2004 Jan 1;103(1):301-8.
Qiang YW, Yao L, Tosato G, Rudikoff S.
Insulin-like growth factor I (IGF-I) is one of several growth factors that promote the growth of MM cells. This study assesses the ability of IGF-I to serve additionally as a chemotactic factor affecting the mobility and invasion of MM cells. Authors demonstrate that IGF-I promotes transmigration through vascular endothelial cells and bone marrow stromal cell lines.

Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study.
Ann Oncol. 2004 Jan;15(1):134-8.
Zervas K, Dimopoulos MA, Hatzicharissi E, Anagnostopoulos A, Papaioannou M, Mitsouli Ch, Panagiotidis P, Korantzis J, Tzilianos M, Maniatis A; Greek Myeloma Study Group.
39 patients with newly diagnosed myeloma were treated with VAD-Doxil + thalidomide 200 mg PO qhs every 28 days x 4 cycles. Response rate was 74% (CR 10%, PR 64%), minor response 8%, and refractory disease 18%. Most important toxicities were cytopenias, DVT (10%), skin rash (5%), and peripheral neuropathy (5%). 2 patients (5%) died because of infection.

Long-term follow-up of idiotype vaccination in human myeloma as a maintenance therapy after high-dose chemotherapy.
Leukemia. 2004 Jan;18(1):139-45.
Coscia M, Mariani S, Battaglio S, Di Bello C, Fiore F, Foglietta M, Pileri A, Boccadoro M, Massaia M.
15 patients with multiple myeloma treated with autologous stem cell transplantation received idiotype vaccination. The idiotype vaccination did not improve the degree of disease response. The median progression-free survival was 40 months, and the overall survival was 82 months, results that were similar to those seen in patients treated with interferon-alpha.

Phase II study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma.
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):88-95.
Zangari M, Anaissie E, Stopeck A, Morimoto A, Tan N, Lancet J, Cooper M, Hannah A, Garcia-Manero G, Faderl S, Kantarjian H, Cherrington J, Albitar M, Giles FJ.
In this study, 27 patients with advanced MM were treated with SU5416, a VEGF receptor 2 inhibitor. Four patients had disease stabilization for at least 4 months. There were no objective responses.

Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m2).
Leukemia. 2004 Jan;18(1):133-8.
Palumbo A, Bringhen S, Bertola A, Cavallo F, Falco P, Massaia M, Bruno B, Rus C, Barbui A, Caravita T, Musto P, Pescosta N, Rossini F, Vignetti M, Boccadoro M.
In this study, 90 patients with newly diagnosed myeloma were treated with two autologous transplants using melphalan 100 mg/m2, and their outcomes were compared with those of a control group of 90 patients treated with melphalan 200 mg/m2. Results favored the higher dose:
  - Rate of complete remission was 35% with MEL100 and 48% with MEL200 (p=0.08)
  - Median event-free survival was 32 months with MEL100 and 42 months with MEL200 group (p<0.005)
  - Median overall survival was similar
  - Toxicity was inferior with MEL100, but transplant-related mortality was similar



Translocation t(11;14) in multiple myeloma: Analysis of translocation breakpoints on der(11) and der(14) chromosomes suggests complex molecular mechanisms of recombination.
Genes Chromosomes Cancer. 2004 Feb;39(2):151-5.
Fenton JA, Pratt G, Rothwell DG, Rawstron AC, Morgan GJ.
These authors describe the characterization of the genomic DNA breakpoints of 2 MM patients with the t(11;14). They show that the IgH translocations are more complex than simple reciprocal events mediated by errors in class-switch recombination. DNA from chromosome band 11q13 joined to already recombined hybrid switch region sequences, and, in 1 case, a further rearrangement occurred at the t(11;14) recombination site.


MARCH 2004

Tumor lysis syndrome in a multiple myeloma treated with thalidomide.
Fuente Ann Oncol. 2004 Mar;15(3):537.
N, Maņe JM, Barcelo R, Muņoz A, Perez-Hoyos T, Lopez-Vivanco G.

Thalidomide neuropathy: clinical, electrophysiological and neuroradiological features.
Acta Neurol Scand. 2004 Mar;109(3):188-93.
Isoardo G, Bergui M, Durelli L, Barbero P, Boccadoro M, Bertola A, Ciaramitaro P, Palumbo A, Bergamasco B, Cocito D.
The authors obtained nerve conduction studies, somatosensory-evoked potentials, and MRI of cervical and dorsal spinal cord MRI in 6 patients with myeloma and thalidomide-induced polyneuropathy. The results indicated that thalidomide induces an axonal length-dependent sensory neuropathy and, less frequently, a ganglionopathy.

Characterization of clonogenic multiple myeloma cells.
Blood. 2004 Mar 15;103(6):2332-6.
Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ.
Human MM cell lines contain a small population (< 5%) of CD138-negative cells with a good clonogenic potential in vitro. The phenotype of these cells resembled that one of post-germinal center B cells, and their clonogenic growth was inhibited by the anti-CD20 monoclonal antibody rituximab. These authors suggested that MM stem cells are CD138-negative B cells with the ability to replicate and differentiate into malignant CD138+ plasma cells.

Identification of genes modulated in multiple myeloma using genetically identical twin samples.
Blood. 2004 Mar 1;103(5):1799-806.
Munshi NC, Hideshima T, Carrasco D, Shammas M, Auclair D, Davies F, Mitsiades N, Mitsiades C, Kim RS, Li C, Rajkumar SV, Fonseca R, Bergsagel L, Chauhan D, Anderson KC.
These authors compared the gene expression profile of plasma cells cells from a MM patient with plasma cells from a genetically identical twin, to eliminate the confounding factor represented by the genetic heterogeneity between individuals. They found 296 up-regulated genes and 103 down-regulated genes.

Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies.
Eur J Haematol. 2004 Mar;72(3):155-65.
Mittelman M, Zeidman A, Kanter P, Katz O, Oster H, Rund D, Neumann D.

Fine-needle aspiration of abdominal fat pad for amyloid detection: a clinically useful test?
Diagn Cytopathol. 2004 Mar;30(3):178-81.
Ansari-Lari MA, Ali SZ.
This study evaluated the use of fine-needle aspiration of abdominal fat pad in 91 consecutive patients, to rule out amyloidosis. The test was positive for amyloidosis in 22% of cases. Sensitivity was 75% and specificity 92%.



Giampaolo Talamo, M.D.