JULY 2005

Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database.
Blood. 2005 Jul 15;106(2):668-72.
Altieri A, Bermejo JL, Hemminki K.
Authors used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for NHL and MM in 4455 offspring whose parents or siblings were affected with different types of lymphoproliferative malignancies. For a parental history of MM, the risk for MM was significantly increased (SIR = 2.5).

The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells.
Blood. 2005 Jul 15;106(2):698-705.
Chen Q, Van der Sluis PC, Boulware D, Hazlehurst LA, Dalton WS.
This study shows that resistance to melphalan in cell lines is due to the enhancement of the interstrand cross-link repair due to the activity of the the Fanconi Anemia/BRCA pathway.

Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma.
Blood. 2005 Jul 1;106(1):296-303.
Bergsagel PL, Kuehl WM, Zhan F, Sawyer J, Barlogie B, Shaughnessy J Jr.
Authors propose that cyclin D dysregulation is an unifying pathogenic event in MM. MM translocations dysregulate:
 - CCND1 (11q13). Biallelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which hyperdiploid.
 - CCND2, targeted by the transcription factors MAF (16q23) and MAFB (20q11). CCND2 expression can be increased either with or without a t(4;14) translocation.
 - CCND3 (6p21)

Positive pregnancy tests in a nongravid, premenopausal woman due to hCG beta-chain production by multiple myeloma.
Am J Clin Pathol. 2005 Jul;124(1):108-12.
Slone SP, Ahmed Z, Cole LA, Elin RJ, Martin AW, Herzig RH, Herzig GP, Miller JJ.
nongravid, premenopausal woman receiving chemotherapy for multiple myeloma had a positive pregnancy test. This was found to be related to human chorionic gonadotropin (hCG) originated from myeloma. Immunohistochemical stains showed that MM cells expressed hCG.

Whole-body MR imaging of bone marrow.
Eur J Radiol. 2005 Jul;55(1):33-40.
Schmidt GP, Schoenberg SO, Reiser MF, Baur-Melnyk A.

Role of MRI for the diagnosis and prognosis of multiple myeloma.
Eur J Radiol. 2005 Jul;55(1):56-63.
Baur-Melnyk A, Buhmann S, Dürr HR, Reiser M.

Superiority of thalidomide and dexamethasone over vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma.
Blood. 2005 Jul 1;106(1):35-9.
Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, de Vivo A, Testoni N, Nicci C, Terragna C, Grafone T, Perrone G, Ceccolini M, Tura S, Baccarani M; Bologna 2002 study.

This is a retrospective matched case-control study of 200 patients with newly diagnosed myeloma, treated with either VAD (100 patients) or thalidomide + dexamethasone (TD, 100 patients) for 4 months as induction therapy before autologous stem cell transplantation. Results:
  - Response rate was 52% with VAD and 76% with TD (p <0.001)
  - Most important toxicities were neutropenia with VAD (12%) and DVT with TD (15%)
  - The median number of collected CD34+ cells/Kg was 10.5 million with VAD and 7.85 million with TD

Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure.
Eur J Haematol. 2005 Jul;75(1):27-33.
Knudsen LM, Nielsen B, Gimsing P, Geisler C.
In this study, 137 myeloma patients who underwent autologous transplant were divided into 3 groups, based on their renal function:
  - Group A (78 patients): normal renal function both at diagnosis and at transplant
  - Group B (30 patients): renal failure (Creat Clear < 60 mL/min) at diagnosis but normal renal function at transplant (n = 30)
  - Group C (29 patients): renal failure both at diagnosis and at transplant
 - Disease response to transplant was similar in the 3 groups
 - Transplant-related mortality was 1% in Group A, 0% in Group B, and 17% in Group C
 - 4 of 8 patients on dialysis before transplant died within the first 100 days after transplant.
 - Patients of Group C had a longer hospitalization, increased need for transfusions, and more frequent infections
 - In Group C, 10 patients had a normalization of renal function after transplant

An elective single autograft with high-dose melphalan: single-center study of 451 patients.
Bone Marrow Transplant. 2005 Jul;36(1):19-24.
Sirohi B, Powles R, Mehta J, Rudin C, Kulkarni S, Horton C, Saso R, Singhal S, Treleaven J.
This is one of the largest studies of autologous stem cell transplant in multiple myeloma, with long-term follow-up. 451 patients, 51% with newly diagnosed disease, underwent a single autologous transplant with melphalan 200 mg/m2. Interferon-alpha2b was given as post-transplant maintenance. Median follow-up was 65 months (range: 0.5-17.7 years). Results:
  - Transplant-related mortality was 6%
  - Response rate was 91%, with 59% complete or near-complete responses
  - Median overall survival was 5.9 years
  - Median event-free survival was 2.4 years
  - Probability of overall survival at 10 years was 31.4%
  - Probability of event-free survival at 10 years was 16.5%



Malignant pleural effusion of multiple myeloma: prognostic factors and outcome.
Leuk Lymphoma. 2005 Aug;46(8):1137-42.
Kamble R, Wilson CS, Fassas A, Desikan R, Siegel DS, Tricot G, Anderson P, Sawyer J, Anaissie E, Barlogie B.
Approximately 80 cases of malignant pleural effusion (MPE) in MM have been reported. These authors reviewed 11 MM patients with MPE. All patients had high-risk disease and complex karyotype including -13 in 9 cases. Patients died at median of 4 months from onset of MPE despite aggressive therapeutic approaches such as stem cell transplant.

CT features of abdominal plasma cell neoplasms.
Eur Radiol. 2005 Aug;15(8):1705-12.
Monill J, Pernas J, Montserrat E, Pérez C, Clavero J, Martinez-Noguera A, Guerrero R, Torrubia S.
This study describes the CT features of abdominal plasma cell neoplasms in 11 patients with plasma cell neoplasms and abdominal involvement. MM was found in 7 patients and extramedullary plasmacytoma in 4 patients. All patients with MM had other areas of extramedullary involvement, including the perirenal space (4), retroperitoneal and pelvic lymph nodes (3), peritoneum (3), liver (2), subcutaneous tissues (2) and kidney (1).

Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results of a prospective study of patients treated with dexamethasone-based regimens and high-dose chemotherapy.
J Clin Oncol. 2005 Aug 1;23(22):5217-23.
Talamo G, Angtuaco E, Walker RC, Dong L, Miceli MH, Zangari M, Tricot G, Barlogie B, Anaissie E.

In a total of 553 myeloma patients treated with dexamethasone-containing chemotherapy, AVN of the femoral head developed in 49 patients (9%). The median time to onset was 12 months (range, 2 to 41 months). Only 4 patients required hip replacement because of AVN. Higher cumulative doses of dexamethasone increased the risk of AVN.

Tc99m-sestaMIBI uptake in nonsecretory multiple myeloma.
Hematology. 2005 Aug;10(4):335-8.
Catalano L, Andretta C, Pace L, Del Vecchio S, Salvatore B, De Rosa G, Buonanno MT, Paone G, Rotoli B.
These authors evaluated the role of Tc99m-sestaMIBI scintigraphy at diagnosis and follow-up of 9 patients with non-seccretory myeloma. They found that Tc99m-sestaMIBI scintigraphy has a high sensitivity (no false positive cases) and 78% specificity (2 of 9 cases were false negative). They advocate a role for this imaging modality in the monitoring of non-secretory myeloma, and they conclude that it should be considered complementary to conventional imaging studies.

Baseline Tc99-MIBI scanning predicts survival in multiple myeloma and helps to differentiate this disease from monoclonal gammopathy of unknown significance.
Haematologica. 2005 Aug;90(8):1141-3.
Martín MG, Romero Colás MS, Dourdil Sahún MV, Olave P, Alba PR, Banzo JB.
These authors obtained baselineTc(99)-MIBI scanning in 43 patients with multiple myeloma and in 31 with MGUS, and they found a correlation between results and patients' survival.

[First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma.
Bone Marrow Transplant. 2005 Aug;36(3):193-8.
Abdelkefi A, Torjman L, Ben Romdhane N, Ladeb S, El Omri H, Ben Othman T, Elloumi M, Bellaj H, Lakhal A, Jeddi R, Aissaouï L, Saad A, Hsaïri M, Boukef K, Dellagi K, Ben Abdeladhim A.
This study has been retracted in June 2009]

High-dose idarubicin, cyclophosphamide and melphalan as conditioning for autologous stem cell transplantation increases treatment-related mortality in patients with multiple myeloma: results of a randomised study.
Br J Haematol. 2005 Aug;130(4):588-94.
Fenk R, Schneider P, Kropff M, Huenerlituerkoglu AN, Steidl U, Aul C, Hildebrandt B, Haas R, Heyll A, Kobbe G; West German Myeloma Study Group.
This is a randomized trial comparing two conditioning regimens for autologous transplants in 56 patients with myeloma:
  - The standard regimen was melphalan 200 mg/m2
  - The intensified regimen consisted of melphalan 200 mg/m2 + cyclophosphamide 120 mg/kg + idarubicin 42 mg/m2
The study was discontinued early, because the intensified regimen was associated with unacceptable toxicity: treatment-related mortality was 20% (vs 0% with the standard regimen, mainly because of infections.

Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma.
Bone Marrow Transplant. 2005 Aug;36(4):315-23.
Neelapu SS, Munshi NC, Jagannath S, Watson TM, Pennington R, Reynolds C, Barlogie B, Kwak LW.
These authors induced tumor-specific T-cells in transplant donors, in the attempt to enhance the graft-vs-myeloma effect. They vaccinated 5 HLA-matched sibling donors with myeloma idiotype proteins from the patients, and gave booster immunizations after the transplant. Outcome:
  - 2 patients died within 30 days from transplant-related complications.
  - 1 patient died after 5.5 years while in complete remission
  - 2 patients were in disease remission 7 years and 8 years after the transplant



Multiple myeloma of the thoracic spine developed at the previous trauma site: case report.
Eur Spine J. 2005 Sep;14(7):698-701.
Erdogan B, Sener L, Kilic D, Bolat F, Altinors N.
This is a case report of a 62-year-old man who initially had a traumatic T7 compression fracture and developed a multiple myeloma two years later at that site. Authors speculate that a preceding trauma may be a causative factor in plasma cell dyscrasias.

Anthropometric characteristics and risk of multiple myeloma.
Epidemiology. 2005 Sep;16(5):691-4.
Blair CK, Cerhan JR, Folsom AR, Ross JA.
Obesity could influence carcinogenesis of MM. Authors prospectively studied the association between anthropometric characteristics and incidence of MM in a sample of 37,083 postmenopausal women. During 16 years of follow up, 95 cases of MM were identified. Women with greater adiposity had an increased risk of MM.

Wnts induce migration and invasion of myeloma plasma cells.
Blood. 2005 Sep 1;106(5):1786-93.
Qiang YW, Walsh K, Yao L, Kedei N, Blumberg PM, Rubin JS, Shaughnessy J Jr, Rudikoff S.
This study identified multiple members of the wingless/int (Wnt) family as promoters of myeloma cell migration and invasion. Wnt-mediated migration was associated with the Wnt/RhoA pathway and did not require the beta-catenin signal. Wnt responsiveness of plasma cells may be involved in disease progression of MM.

Molecular pathogenesis and a consequent classification of multiple myeloma.
J Clin Oncol. 2005 Sep 10;23(26):6333-8.
Bergsagel PL, Kuehl WM.

Jumping translocations in multiple myeloma.
Cancer Genet Cytogenet. 2005 Sep;161(2):159-63.
Jamet D, Marzin Y, Douet-Guilbert N, Morel F, Le Bris MJ, Herry A, Banzakour S, Bourquard P, Morice P, Abgrall JF, Berthou C, De Braekeleer M.
Jumping translocations (JT) are nonreciprocal translocations which result in  extra copies of a same donor segment on different recipient chromosomes. Authors analyzed JT in 6 MM patients and reviewed the literature in other 24 patients. They found that breakpoints on the recipient chromosomes were pericentromeric in 46% of cases and telomeric in 40% of cases. Since telomeres consist of (TTAGGG)n tandem DNA repeats that are also present in the pericentromeric regions (interstitial telomeric sequences), they suggest that JT are the product of illegitimate recombination between telomeric and and interstitial repeat sequences.

Clinical usefulness of free light chain concentration as a tumor marker in multiple myeloma.
Ann Hematol. 2005 Sep;84(9):588-93.
Kang SY, Suh JT, Lee HJ, Yoon HJ, Lee WI.

Recent clinical studies of the immunomodulatory drug (IMiD) lenalidomide.
Br J Cancer. 2005 Sep 19;93(6):613-9.
Bartlett JB, Tozer A, Stirling D, Zeldis JB.

The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy.
Haematologica. 2005 Sep;90(9):1287-8.
Knop S, Straka C, Haen M, Schwedes R, Hebart H, Einsele H.
This is a dose-escalation study of bendamustine in 31 patients with multiple myeloma that had progressed after high-dose chemotherapy. The maximal tolerated dose was 100 mg/m2 on days 1-2. The response rate was 55%, and the median progression-free survival was 26 weeks (range 0-61). Toxicity was mainly hematologic.

2-Methoxyestradiol at low dose induces differentiation of myeloma cells.
Leuk Res. 2005 Sep;29(9):1059-67.
Hou J, Xiong H, Gao W, Jiang H.
2ME2 induced maturation of myeloma cells and increased the secretion of light chain proteins.

Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma.
Hematology. 2005;10 Suppl 1:117-26.
Shaughnessy J.



Giampaolo Talamo, MD