Myeloma and Lymphoma: Stem-Cell Transplantation in Myeloma

Posted by James

Speaker: Thomas Shea, University of North Carolina School of Medicine, Chapel Hill, North Carolina

Melphalan. High-dose chemotherapy appears to be commonly used to treat MM. Researchers compared the two most widely used conditioning regimens in a prospective, randomized trial before autologous stem-cell transplantation in patients with newly diagnosed symptomatic MM. The patients were younger than 65 years old. Those in arm A received 8 gray (Gy) of total-body irradiation (TBI) plus 140 mg/m² of melphalan; those in arm B received 200 mg/m² of melphalan (Alkeran®). A total of 282 evaluable patients were compared.

The results showed that melphalan 200 mg/m² was less toxic and at least as effective a conditioning regimen as 8 Gy of TBI with melphalan140 mg/m². This regimen should be considered the standard of care before autologous stem-cell transplantation in MM. cialis canadian pharmacy

A randomized trial of high-dose chemotherapy with mel-phalan 140 mg/m² plus TBI, followed by either one or two successive autologous stem-cell transplantations, was conducted. A complete or a very good partial response was achieved by 42% of patients in the single-transplant group and by 50% of patients in the double-transplant group.

The investigators concluded that double transplantation improved overall survival among MM patients, compared with single autologous stem-cell transplantation, after high-dose chemotherapy, especially in patients who did not have a very good partial response after undergoing a single transplantation.

Autologous and Allogeneic Transplantation. The use of autologous versus allogeneic transplantation is an important consideration in MM. A study was conducted to compare the results of autologous and allogeneic peripheral hematopoietic stem-cell transplantation (HSCT) in 87 patients with MM using a myeloablative preparative regimen. Autologous transplantation (n = 70) led to a lower 100-day procedure-related mortality (4°%) than did allogeneic transplantation (18°%) (P = .02).

Complete responses were seen more often in allogeneic recipients (64%) than in autologous recipients (34%) (P = .09). For the autologous recipients, survival at one year was 86% but fell to 50% at four years. For the allogeneic recipients, survival at one and at four years remained at 64%. Thus, for patients who survived more than one year, the four-year survival rate was superior in the allogeneic recipients (100%) than in the autologous recipients (58%) (P = .02). silagra

A trend toward higher relapse was seen with autologous transplantation (73%) than with allogeneic transplantation (37%) (P = .1). Although autologous HSCT is associated with a lower rate of transplantation-related mortality, allogeneic HSCT has an accepted mortality rate and is more likely to provide a sustained response. Allogeneic HSCT may be suitable in younger patients, soon after diagnosis, and in those with chemotherapy-sensitive disease.

Follicular, Large-Cell, and Mantle-Cell Lymphoma: Overall Biology and Pathology

Speaker: Randy D. Gascoyne, British Columbia Cancer Agency, Vancouver, British Columbia

Follicular lymphoma is the most common subtype of non-Hodgkin’s lymphoma (NHL) in North America.

Diffuse, large B-cell lymphoma is the most common lymphoma subtype. It comprises at least two diseases: germinal center B cell-like (GCB) disease and non-germinal center activated B cell-like (ABC) disease. Genomic imbalances have an independent predictive value and add to the molecular predictor.

Mantle-cell lymphoma represents about 6% of all NHLs and comprises small B-cell lymphoma with aggressive, relentless clinical behavior. The proliferation signature represents an integrator of oncogenic events. online pharmacy prescription drugs

Mantle-cell lymphomas are remarkably consistent in their phenotype. They are typically CD5-positive, CD10-negative, CD23-negative B-cell NHLs that strongly express surface immunoglobulin D (IgD) or M (IgM), predominantly of the gamma light-chain type.

Mantle-cell lymphoma is associated with a recurring cyto-genetic abnormality, t(11;14)(q13;q32), that involves the bcl-1/PRAD-1 gene. This abnormality results in the over-expression of cyclin D1 protein. Although cyclin D1-positive lymphomas other than mantle-cell lymphoma have been encountered, several studies indicate that the overexpression of the PRAD-1/cyclin D1 gene is a highly specific marker of mantle-cell lymphoma. Microarray studies have revealed the differential expression of several genes in mantle-cell lym-phoma, but it is unknown which of these differences are dependent on the transformed mantle cell itself or on the tumor microenvironment.

We need more knowledge to understand the biology of mantle-cell lymphoma to improve therapy. Genome-wide analysis tools should provide additional insights.

Therapy for Follicular Lymphoma

Speaker: David G. Maloney, Fred Hutchinson Cancer Research Center, Seattle, Washington

Follicular lymphoma represents 22% of new NHL diagnoses. The most common forms are indolent or low-grade. There is a progressive transformation of the follicular center B cell. The human bcl-2 gene is an oncogene candidate, which is involved in the t(14;18) translocation specifically associated with follicular and diffuse B-cell lymphomas. tadacip

Rituximab. Rituximab (Rituxan^®, Genentech/Biogen Idec) has changed the treatment paradigm of patients with B-cell lymphomas. This monoclonal antibody is considered the first effective targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of lymphoproliferative disorders. Despite its efficacy and safety profile, sustained complete remissions have been documented in a relatively small proportion of patients treated with rituximab monotherapy.

To improve antitumor activity, initial strategies combined rit-uximab with standard chemotherapy drugs; this approach led to higher response rates; improved disease-free survival; and, in some cases (i.e., with diffuse large B-cell lymphoma), prolonged overall survival. Although rituximab has been incorporated into multiple chemotherapy regimens, such as CVP (cyclophosphamide, vincristine, prednisone), CHOP (cyclophosphamide, hydroxydaunomycin, Oncovin® [vincristine], prednisone), and FND (fludarabine, mitoxantrone, dexamethasone), many lymphoma patients either experience relapse after an initial response or do not respond because of either intrinsic or acquired resistance.

Scientific efforts are being focused toward developing new strategies to improve rituximab activity. A review of past, ongoing, and future research with a diverse group of exciting novel agents follows next. tadalis sx

E1496 Trial. E1496 was a phase 3 trial of CVP chemotherapy with or without maintenance therapy with rituximab. Intermediate-risk patients with follicular lymphoma receiving CVP plus rituximab maintenance therapy had a one-year overall survival rate of 89% and a two-year progression-free survival rate of 70%. The patients received four cycles every six months for two years. Thus, there is a benefit of adding rituximab sequentially after chemotherapy. Rituximab delays the TTP in the intermediate-risk and high-risk groups of patients.

Rituximab-CHOP Trial. A phase 3 study of rituxi-mab-CHOP (R-CHOP) as a first-line therapy for follicular lym-phoma demonstrated a favorable median time-to-treatment failure in 68 months versus 21 months with CHOP alone. The median progression-free survival rates were 50 months with R-CHOP and 15 months with CHOP.

M39023 Trial. The M39023 study utilized MCP (mitox-antrone, chlorambucil, prednisolone) chemotherapy for six cycles every four weeks and rituximab-MCP (R-MCP) for six cycles every four weeks. This was followed by restaging; one group of patients received MCP for two cycles every four weeks, and R-MCP was given to patients with stage III/IV follicular lymphoma for two cycles every four weeks. The median ages were 62 and 61 years, respectively.

Remission rates for the intent-to-treat population and clinical remission rates for the R-MCP patients and those with follicu-lar lymphoma who received MCP were 92.4% and 75%, respectively (P < .0001), and 49.5% and 25%, respectively (P < .0001).

Progression-free survival was significantly prolonged with R-MCP (88.5% at 19.7 months; the median was not reached), compared with MCP (55% at 19.7 months).

This study confirms the recently published data of rituximab plus chemotherapy in the first-line treatment of indolent NHL. R-MCP may become the new standard, especially for elderly patients with follicular lymphoma. UK viagra

Iodine 131-Tositumomab Trial. I-Tositumomab (anti-CD20 mAb) was initially studied in patients with grade 1 (70%) and grade 2 follicular lymphoma (29%). The outcomes were good; 95% of patients responded with at least a partial remission, and 75% had complete remissions.

Another study using CHOP, followed by I-tositumomab for untreated indolent NHL, showed excellent two-year overall and progression-free survival (97% and 81%, respectively).