APRIL 2004

The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant.
Br J Haematol. 2004 Apr;125(1):64-8.
Chang H, Sloan S, Li D, Zhuang L, Yi QL, Chen CI, Reece D, Chun K, Keith Stewart A.

128 myeloma patients treated with autologous stem cell transplantation were studied for the t(11;14) and t(4;14) translocations. t(11;14) was present in 16 of 125 (12.8%) and t(4;14) in 15 of 120 (12.5%) patients. The t(11;14) translocation had a neutral impact on prognosis, whereas patients with t(4;14) had a shorter median progression-free survival (9.9 vs 25.8 months, p= 0.0003) and shorter median overall survival (18.3 vs 48.1 months, p <0.0001) than the rest of the patients.

Dialysis-dependent renal failure in patients with myeloma can be reversed by high-dose myeloablative therapy and autotransplant.
Bone Marrow Transplant. 2004 Apr;33(8):823-8.
Lee CK, Zangari M, Barlogie B, Fassas A, van Rhee F, Thertulien R, Talamo G, Muwalla F, Anaissie E, Hollmig K, Tricot G.
In this study, 59 myeloma patients on dialysis underwent autologous transplant. 37 patients were on dialysis at least 6 months. The results showed that renal failure can be reversible after transplant. Recovery of renal function depended on time on dialysis and response to transplant. Results:
  - Of 54 evaluable patients,13 (24%) became dialysis independent, after a median of 4 months post-SCT (range: 1-16 months).
  - Recovery of renal function occurred in 12 of 36 patients (33%) on dialysis for <6 months and only 1 of 18 patients (6%) on dialysis for >6 months
  - Recovery of renal function occurred in 12 of 31 patients (39%) in >PR after SCT and only 1 of 21 patients (5%) in PR or less after SCT
  - The 5-year overall survival was 36%, and the 5-year event-free survival was 24%

Free immunoglobulin light-chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-hr urinary light-chain excretion.
Am J Hematol. 2004 Apr;75(4):246-8.
Alyanakian MA, Abbas A, Delarue R, Arnulf B, Aucouturier P.

Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma.
Am J Clin Pathol. 2004 Apr;121(4):482-8.
Lin P, Owens R, Tricot G, Wilson CS.
Flow cytometry was obtained in the bone marrow aspirates of 306 myeloma patients. Antigen expression was moderate-bright as follows:
  - CD56: 72%
  - CD117: 18%
  - CD20: 9% (target of rituximab)
  - CD45: 9%
  - CD52: 5% (target of alentuzumab)
  - CD19: <1%

Early response predicts thalidomide efficiency in patients with advanced multiple myeloma.
Br J Haematol. 2004 Apr;125(2):149-55.
Waage A, Gimsing P, Juliusson G, Turesson I, Gulbrandsen N, Eriksson T, Hjorth M, Nielsen JL, Lenhoff S, Westin J, Wislöff F; Nordic Myeloma Study Group.
65  patients with refractory myeloma were treated with thalidomide at a dose of 200 mg/day, escalated to 800 mg. Response: 14% PR, 6% CR, 14% minor response. Median survival was 12 months.

Thalidomide in patients with multiple myeloma and renal failure.
Br J Haematol. 2004 Apr;125(1):96-7.
Fakhouri F, Guerraoui H, Presne C, Peltier J, Delarue R, Muret P, Knebelmann B.

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma.
Leukemia. 2004 Apr;18(4):856-63.
García-Sanz R, González-Porras JR, Hernández JM, Polo-Zarzuela M, Sureda A, Barrenetxea C, Palomera L, López R, Grande-García C, Alegre A, Vargas-Pabón M, Gutiérrez ON, Rodríguez JA, San Miguel JF.
71 patients with relapsed or refractory myeloma were treated with  thalidomide 200-800 mg/day, cyclophosphamide 50 mg/day, and dexamethasone 40 mg/day, 4 days every 3 weeks. Response rate at 3 months was 83%: complete response 2%, partial response 55%, minor response 26%. CR rate was 10% at 6 months. Event free survival at 2 years was 57%. Venous thromboembolism was seen in 7% of patients.

Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone.
Blood. 2004 Apr 15;103(8):3138-47.
Strömberg T, Dimberg A, Hammarberg A, Carlson K, Osterborg A, Nilsson K, Jernberg-Wiklund H.


MAY 2004

Benefit and timing of second transplantations in multiple myeloma: clinical findings and methodological limitations in a European Group for Blood and Marrow Transplantation registry study.
J Clin Oncol. 2004 May 1;22(9):1674-81.
Morris C, Iacobelli S, Brand R, Bjorkstrand B, Drake M, Niederwieser D, Gahrton G; Chronic Leukaemia Working Party Myeloma Subcommittee, European Group for Blood and Marrow Transplantation.
This study reviewed 7,452 patients treated with autologous transplants, either planned tandem transplants or not. Results were analyzed on an intention-to-treat basis. Of note, the transplantation rate in the group of planned transplants was only 55% (1,469 of 2,655 patients). The median survival from transplant was 60 months for the "planned" group, vs 51 months for the remainder group. The authors found that, in order to improve survival of tandem autologous transplants, the second transplant should be performed before relapse and within 6-12 months of the first transplant.

Light-chain only multiple myeloma is due to the absence of functional (productive) rearrangement of the IgH gene at the DNA level.
Blood. 2004 May 15;103(10):3869-75.
Magrangeas F, Cormier ML, Descamps G, Gouy N, Lodé L, Mellerin MP, Harousseau JL, Bataille R, Minvielle S, Avet-Loiseau H.
Myeloma cells secreting heavy chains have a legitimate functional IgH rearrangement. Using fiber-fluorescent in situ hybridization, these authors demonstrated that malignant plasma cells of light chain myeloma do not have a functional IgH recombination. One IgH allele has a germline configuration (including the DJ region), and the other allele is involved in an illegitimate recombination. Interestingly, most translocations occurred at or close to the switch regions. Plasma cells of light chain myeloma do not have a legitimate IgH rearrangement at the DNA level, presumably because of an abnormal IgH gene recombination during B-cell maturation.

Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma.
Haematologica. 2004 May;89(5):557-66.
Fenk R, Ak M, Kobbe G, Steidl U, Arnold C, Korthals M, Hünerlitürkoglu A, Rohr UP, Kliszewski S, Bernhardt A, Haas R, Kronenwett R.
This study evaluates the use of PCR for IgH to detect minimal residual disease after stem cell transplantation in 11 patients with multiple myeloma. Monitoring of quantitative PRC was predictive of disease remission and relapse.

Induction with oral chemotherapy (CID) followed by early autologous stem cell transplantation for de novo multiple myeloma patients.
Hematol J. 2004 May;5(3):216-21.
Spencer A, Seldon M, Deveridge S, Cobcroft R, Cull G, Marlton P, Enno A, Gill D.
36 patients with newly diagnosed multiple myeloma received chemotherapy with CID (Cyclophosphamide, Idarubicin, Dexamethasone), given orally, as induction therapy before stem cell transplantation. Response rate was 66% (CR 9%). Overall survival at 4 years was 77%.

Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma.
Br J Haematol. 2004 May;125(4):470-6.
Hussein MA, Saleh M, Ravandi F, Mason J, Rifkin RM, Ellison R.
This is a phase II study of arsenic trioxide in 24 patients with relapsed or refractory MM. Patients received arsenic trioxide 0.25 mg/kg/day for 5 days/week during the first 2 weeks of a 28-day cycle. 8 of 24 patients (33%) had reductions in serum M protein levels by at least 25%, and 6 patients (25%) had stable disease. The median duration of response was 130 days.

Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma.
Blood. 2004 May 1;103(9):3271-7.
Alsina M, Fonseca R, Wilson EF, Belle AN, Gerbino E, Price-Troska T, Overton RM, Ahmann G, Bruzek LM, Adjei AA, Kaufmann SH, Wright JJ, Sullivan D, Djulbegovic B, Cantor AB, Greipp PR, Dalton WS, Sebti SM.
This study evaluated the activity of the farnesyltransferase inhibitor tipifarnib (Zarnestra) in 43 patients with MM. Dose: 300 mg PO bid for 3 weeks every 4 weeks. 64% of patients had disease stabilization. The most common toxicity was fatigue (66%).


JUNE 2004

A common clonal origin of nodal marginal zone B-cell lymphoma and plasma cell myeloma demonstrating different immunophenotypes: a case report of composite lymphoma.
Diagn Mol Pathol. 2004 Jun;13(2):75-80.
Saito H, Oka K, Nakamura N, Nagayama R, Hakozaki H, Mori N.
This is a case report of an 83-year-old male with MM and nodal marginal zone lymphoma in a cervical lymph node. Bone marrow biopsy showed MM, with plasma cells positive for IgA-kappa, while cervical LN biopsy revealed nodal marginal zone B-cell lymphoma, with lymphoma cells positive for IgG-lambda. Interestingly, Southern blot of the IgH gene showed same clonal rearrangement in both LN and bone marrow, and sequence analyses of the IgH gene showed an identical sequence of CDR3 in both samples. Thus, authors demonstrated a common clonal origin of the nodal MZL and MM.

Etoposide, methylprednisolone, cytarabine and cisplatin successfully cytoreduces resistant myeloma patients and mobilizes them for transplant without adverse effects.
Br J Haematol. 2004 Jun;125(6):756-65.
D'Sa S, Yong K, Kyriakou C, Bhattacharya S, Peggs KS, Foulkes B, Watts MJ, Ings SJ, Ardeshna KM, Goldstone AH, Williams CD.
42 patients with myeloma, most of them resistant to VAD chemotherapy, were treated with ESHAP (Etoposide, Methylprednisolone, Cytarabine, Cisplatin) as second-line therapy. Response rate was 67%, and 58% of those with minor response converted to PR. Stem cell mobilization was done in 32 patients, and 87% of them collected >2 million CD34+ cells/Kg. Overall survival at 4 years was 62%, not significantly different from historical controls with VAD-responsive patients.

The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma.
Blood. 2004 Jun 1;103(11):4362-4.
Lokhorst HM, Wu K, Verdonck LF, Laterveer LL, van de Donk NW, van Oers MH, Cornelissen JJ, Schattenberg AV.
In this study, 54 patients with myeloma in relapse after allogeneic SCT received DLI. Results:
  - Response rate was 52%: PR 35%, CR 17%
  - Progression-free survival: 19 months
  - Overall survival: 23 months
The strongest predictors of response were acute GVHD (57%) and chronic GVHD (47%).



Giampaolo Talamo, M.D.