Mantle cell lymphoma (MCL), one of several subtypes of B-cell (non-Hodgkin) lymphoma found in the lymph nodes, bone marrow, blood, spleen, and gastrointestinal system, is caused by a malignant transformation of a B lymphocyte in the outer edge of a lymph node follicle called the mantle zone.

According to the The Leukemia & Lymphoma Society, there are about 59,000 new cases of non-Hodgkin lymphoma diagnosed in the United States. About 6% of these new cases, or about 3,500 annually, are diagnosed as MCL. The disease occurs more frequently in older adults ? the average age at diagnosis is the mid-60s. While recent treatment advances have improved outcomes over the last several decades for patients with mantle cell lymphoma, it is still associated with an overall poor prognosis. The median progression-free period for patients is about 20 months with a median survival of three to four years.

A previous study conducted by the European Mantle Cell Lymphoma Network (MCL net) found that high-dose chemotherapy followed by an autologous stem cell transplant resulted in a significant increase in progression-free survival in patients with advanced stage mantle cell lymphoma. Additionally, other studies have found that the addition of rituximab to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without high dose ARA-C (cytarabine) prior to an autologous stem cell transplant may significantly improve remission rates and progression-free survival. One specific study from the GELA (Groupe d?Etude des Lymphomes de I?Adulte) that evaluated a regimen of rituximab and CHOP chemotherapy followed by rituximab and DHAP chemotherapy (dexamethasone, cytarabine, and cisplatin) prior to an autologous stem cell transplant resulted in an overall response rate of 95% and a complete response rate of 61%, which translated into a median event-free survival rate of 83 months (6.9 years) and an overall survival rate of 75% at five years.

In order to confirm the hypothesis that a high-dose ARA-C (cytarabine)-based chemotherapy induction regimen prior to an autologous stem cell transplant provides superior outcomes, researchers from MCL Net initiated a randomized study, led by Professors Olivier Hermine and Martin Dreyling, in which patients younger than 65 years with previously untreated stage 2, 3, or 4 mantle cell lymphoma were randomized to one of two treatment arms. In the control arm of the study, patients received six courses of rituximab and CHOP chemotherapy followed by high-dose myeloablative radiochemotherapy and an autologous stem cell transplant, a procedure in which patients receive an infusion of their own stem cells. In the experimental arm of the study, patients received alternating courses of CHOP chemotherapy and DHAP chemotherapy three times plus rituximab followed by a high-dose ARA-C myeloablative chemotherapy regimen and an autologous stem cell transplant.[1]

The primary endpoint of the study was time to treatment failure (TTF). Stable disease after induction therapy as well as progression or death from any causes were considered treatment failures. Randomization in the study was stopped as soon as a significant difference was observed between the two study arms.

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After a median follow up of 27 months, TTF had not yet been reached in the ARA-C arm as compared with 49 months in the control arm. At three years, the survival rate was 79% in the control arm and 80% in the ARA-C arm. Overall survival was found to be similar in both treatment arms with median overall survival not yet reached.

“Results of this study confirm that there is a new standard of care for the treatment of younger patients with previously untreated mantle cell lymphoma,” said lead study author Olivier Hermine, MD, PhD, Professor, Head of the Hematological Department, Necker Hospital in Paris. “High-dose ARA-C chemotherapy should be part of the induction therapy along with rituximab and CHOP chemotherapy prior to an autologous stem cell transplant in order to improve outcomes without an increase in toxicity in these patients.”

The data of this research was presented during the 52nd Annual Meeting of the American Society of Hematology in Orlando, Florida (December 4 ? 7, 2010).

Fore more information:
[1] Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT in Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net) [Abstract 110]

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