Predicting long-term (> or = 5 years) event-free survival in multiple myeloma patients following planned tandem autotransplants.
Tricot G, Spencer T, Sawyer J, Spoon D, Desikan R, Fassas A, Badros A, Zangari M, Munshi N, Anaissie E, Toor A, Barlogie B.
Br J Haematol. 2002 Jan;116(1):211-7.
This study analyzed prognostic factors for long-term survival in 515 consecutive patients who underwent tandem transplants and had a follow up of at least 5 years. Multivariate analysis identified several factors associated with event-free survival of at least 5 years:
  - Beta-2 microglobulin = or < 2.5 mg/l at time of first transplant
  - Absence of chromosome 11 and 13 abnormalities
  - Less than 12 months of induction therapy
Follow-up data were consistent with cure in those myeloma patients in complete remission for at least 7 years post-transplant, and re-establishment of an MGUS status in those in partial remission at 7 years post-transplant.

Myeloablative treatments for multiple myeloma: update of a comparative study of different regimens used in patients from the Spanish registry for transplantation in multiple myeloma.
Leuk Lymphoma. 2002 Jan;43(1):67-74.
Lahuerta JJ, Grande C, Blade J, Martínez-López J, de la Serna J, Alegre A, Garcia LJ, Caballero D, de la Rubia J, Marín J, Perez-Lopez C, Sureda A, Escudero A, Cabrera R, Conde E, García-Ruiz JC, Pérez-Equiza K, Hernandez F, Palomera L, León A, Giraldo P, Solano C, Bargay J, San MJ; Spanish Multiple Myeloma Group.
This study evaluated outcomes of 4 different conditioning regimen used for autologous SCT in MM:
  - MEL200: Melphalan 200 mg/m2 (472 patients)
  - MEL140+TBI: - Melphalan 140 mg/m2 + Total Body Irradiation (135 patients)
  - BU-MEL: Busulfan 12 mg/Kg + Melphalan 140 mg/m2 (186 patients)
  - BU-CY: Busulphan 14 mg/Kg + Cyclophosphamide 120 mg/Kg (28 patients)
There were no significant differences between the 4 conditioning regimens, in terms of hematological recovery and transplant-related mortality. Response rate was 100% with BU-MEL and 86-93% in the other groups (p<0.05). Differences in event-free survival and overall survival did not reach statistical significance.

An unusual presentation of plasma cell dyscrasias: cardiac tamponade due to myelomatous infiltration.
Leuk Lymphoma. 2002 Jan;43(1):145-8.
Arat M, Ulusoy V, Demirer T, Uysal AV, Ozcan M, Dinçer S, Ilhan O, Koç H.
These authors report 3 cases of MM with pericardial involvement. The fluid obtained by pericardiocentesis showed infiltration with plasma cells in 1 of the 3 patients. In the other two patients the pericardial involvement was proven by biopsy. All these 3 patients died of progressive disease without any response to chemotherapy.

Case report: testicular secondary localization of a multiple myeloma.
Int Urol Nephrol. 2002;33(1):101-2.
de Rose AF, Giglio M, Naselli A, Truini M, Carmignani G.
This is a case report of a 61-year-old man who had recurrent MM and presented with a right testicular mass.

Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma.
Br J Haematol. 2002 Jan;116(1):202-10.
Barbui AM, Galli M, Dotti G, Belli N, Borleri G, Gritti G, Bellavita P, Viero P, Comotti B, Barbui T, Rambaldi A.
In this study, 60 patients with newly diagnosed multiple myeloma were randomized to receive either unmanipulated or purged stem cells. Negative selection was obtained in vitro by monoclonal antibodies, in order to  eliminate contaminating neoplastic cells. In unmanipulated apheresis products, these authors found a median of 1 tumor cell per 100 normal cells (range: 10-10,000), and manipulation in vitro obtained a 3-4 log reduction. Despite the purging, all patients had minimal residual disease by PCR after stem cell transplant. At 3 years, the event-free survival was 40% in the non-purged arm and 72% in the purged arm (p= 0.05), and there was no difference in overall survival (83% in both arms).



IL-6 transgenic mouse model for extraosseous plasmacytoma.
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1509-14.
Kovalchuk AL, Kim JS, Park SS, Coleman AE, Ward JM, Morse HC 3rd, Kishimoto T, Potter M, Janz S.
IL-6 is plays an important role in growth, differentiation, and survival of B cells. These authors tested the contribution of IL-6 to the development of extramedullary (extraosseous) plasmacytomas (PCT) by generating BALB/c mice carrying an IL-6 transgene. All mice developed plasmacytosis and lymphoproliferation. By 18 months of age, over half developed readily transplantable PCT in lymph nodes, Peyer's patches, and occasionally spleen. These neoplasms had a t(12;15) translocation. Surprisingly, about 30% of the mice developed germinal center-derived NHL (follicular and diffuse large cell B cell lymphomas), that often coexisted with PCT.

The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase II: a Southwest Oncology Group study.
Invest New Drugs. 2002 Feb;20(1):117-21.
Weick JK, Crowley JJ, Hussein MA, Moore DF, Barlogie B; Southwest Oncology Group.
SWOG-9803 evaluated gemcitabine (1,000 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle) in 29 patients with resistant or relapsing multiple myeloma. No responses were seen. Stable disease was observed in 16 patients (57%). Median survival was 8 months.

Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial.
Blood. 2002 Feb 1;99(3):731-5.
Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F, Sotto JJ, Guilhot F, Marit G, Doyen C, Jaubert J, Fuzibet JG, François S, Benboubker L, Monconduit M, Voillat L, Macro M, Berthou C, Dorvaux V, Pignon B, Rio B, Matthes T, Casassus P, Caillot D, Najman N, Grosbois B, Bataille R, Harousseau JL; Intergroupe Francophone du Myélome.
This is a prospective and randomized trial that compared 2 conditioning regimens:
  - Melphalan 140 mg/m2 + TBI 8 Gy (140 patients)
  - Melphalan 200 mg/m2 (142 patients)
Mel 200 was the winner, because it was less toxic and at least as effective as Mel 140 + TBI.
  - The duration of neutropenia and thrombocytopenia was shorter
  - The transfusion requirements lower
  - The median duration of hospitalization was shorter
  - The incidence of severe mucositis was decreased
  - EFS was similar (20.5 vs 21 months)
  - Overall survival at 45 months was improved (65.8% vs 45.5%, p=0.05)


MARCH 2002

Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells.
Blood. 2002 Mar 1;99(5):1745-57.
Zhan F, Hardin J, Kordsmeier B, Bumm K, Zheng M, Tian E, Sanderson R, Yang Y, Wilson C, Zangari M, Anaissie E, Morris C, Muwalla F, van Rhee F, Fassas A, Crowley J, Tricot G, Barlogie B, Shaughnessy J Jr.
These authors performed a gene expression profiling using high-density oligonucleotide microarrays interrogating about 6800 genes in plasma cells from 74 patients with newly diagnosed MM, 5 with MGUS, 31 healthy subjects, and 7 MM cell lines. 4 distinct subgroups of MM (MM1, MM2, MM3, and MM4) were identified. The expression pattern of MM1 was similar to normal PCs and MGUS, whereas MM4 was similar to MM cell lines. The M4 subgroup was associated with poor prognosis, abnormal karyotype, and high serum beta2-microglobulin levels. 120 candidate genes were identified that discriminated normal and malignant plasma cells. Many of those genes are involved in cell adhesion, apoptosis, cell cycle, signaling, and transcription. Gene expression profiling can be used for a gene-based classification system for MM.

IgM myeloma: a report of four cases.
Ann Hematol. 2002 Mar;81(3):136-9.
Dierlamm T, Laack E, Dierlamm J, Fiedler W, Hossfeld DK.

Extended survival in advanced-stage multiple myeloma patients treated with gallium nitrate.
Leuk Lymphoma. 2002 Mar;43(3):603-5.
Niesvizkya R, Choy CG, Siegel D, Lyons L, Michaeli J.
This study identified a group of patients with remarkably prolonged survival after M-2 chemotherapy and adjuvant gallium nitrate (GN) for osteolysis. A retrospective review compared the outcome of 167 patients treated with the M-2 regimen with a cohort of 13 patients (8%) treated with the M-2 protocol + GN. Median survival (from the time of diagnosis) in patients treated with the M-2 regimen was 48 months, while median survival for patients treated with M-2 + GN was 87+ months, a result that markedly exceeded expectations. The authors believed that the administration of GN led to a positive impact on survival of MM patients.

Initial results in the assessment of multiple myeloma using 18F-FDG PET.
Eur J Nucl Med Mol Imaging. 2002 Mar;29(3):361-6.
Schirrmeister H, Bommer M, Buck AK, Müller S, Messer P, Bunjes D, Döhner H, Bergmann L, Reske SN.
This study investigated the appearance of bone lesions on FDG-PET in 28 patients with multiple myeloma and 15 patients with solitary plasmacytoma, and related the findings to those of radiographs, MRI, and CT. Focally increased tracer uptake was observed in 38 of 41 (93%) osteolytic bone lesions in 23 patients. In addition, 71 additional bone lesions were detected in 14 patients with negative radiographs. Findings at FDG-PET influenced clinical management in 5 (14%) patients. FDG-PET proved highly accurate in detecting multiple myeloma, and it revealed a greater extent of disease than routine radiographs in 14 of 23 (61%) patients with lytic bone lesions. FDG-PET is useful in the initial staging of solitary plasmacytoma.

Minimal residual disease monitoring in multiple myeloma.
Best Pract Res Clin Haematol. 2002 Mar;15(1):197-222.
Davies FE, Rawstron AC, Owen RG, Morgan GJ.

Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning.
J Clin Oncol. 2002 Mar 1;20(5):1295-303.
Badros A, Barlogie B, Siegel E, Cottler-Fox M, Zangari M, Fassas A, Morris C, Anaissie E, Van Rhee F, Tricot G.
In this study, 31 patients with relapsed multiple myeloma received a nonmyeloablative allogeneic stem cell transplantation, using a melphalan-based conditioning regimen. 25 patients had HLA-matched siblings, and 6 patients had unrelated donors. Results:
  - At day 100, 89% of patients were full donor chimeras, 1 patient was a mixed chimera, and 2 had autologous reconstitution
  - CR/near CR was 61%
  - Transplant-related mortality: 9 patients (29%)
  - Median overall survival: 15 months
These results should be interpreted in the context of high-risk disease, often leading to death in the order of months instead of years.



Giampaolo Talamo, MD