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According to a study published in the Annals of Oncology, treatment with high-dose sequential chemotherapy and autologous stem cell transplantation may benefit patients with relapsed aggressive non-Hodgkin’s lymphoma (NHL); patients with refractory aggressive NHL do not appear to achieve the same benefit.

Non-Hodgkin’s lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system, which includes the spleen, thymus, tonsils, bone marrow, lymph nodes, and circulating immune cells. Lymphocytes are the main cells in the lymph system and exist in two forms: B and T-cells. Each of these cells serves a specific function in aiding the body fight infection. In NHL, an excessive amount of atypical (cancerous) lymphocytes accumulates in the lymph system. These lymphocytes can crowd and suppress the formation and function of other immune and blood cells.

NHL is categorized by the type of lymphocyte it involves and further defined by the rate at which the cancer grows. The appearance of the cells under a microscope indicates the growth rate. High-grade or aggressive NHL is the fastest growing, whereas low-grade or indolent lymphoma develops slowest. Refractory lymphoma is lymphoma that never responded or has stopped responding to standard therapies. Relapsed lymphoma is lymphoma that has returned after successful initial treatment.

Relapsed or refractory aggressive NHL is often treated with high-dose chemotherapy and stem cell transplantation. Treatment with high-dose chemotherapy kills more lymphoma cells than moderate doses. However, high-dose chemotherapy also results in more side effects, particularly to the blood-producing hematopoietic stem cells. Hematopoietic stem cells are immature blood cells produced in the bone marrow that mature into red blood cells (which carry oxygen to tissues), white blood cells (which fight infection), and platelets (which aid in blood clotting). An autologous stem cell transplant involves the collection of a patient’s own stem cells prior to treatment and re-infusion of the “harvested” stem cells after high-dose chemotherapy; re-infusion restores depleted blood cell levels.

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Although high-dose chemotherapy and autologous stem cell transplant improves survival in relapsed and refractory NHL, many patients eventually relapse after this treatment. In order to determine whether high-dose sequential chemotherapy (a more intensive approach to delivering high-dose chemotherapy) followed by autologous stem cell transplant further improves NHL outcomes, researchers in Germany conducted a phase II clinical trial. The study enrolled 57 NHL patients: 23 who had not responded to initial treatment or who had only briefly responded to initial treatment (refractory NHL) and 34 in whom NHL had come back after a period of no detectable lymphoma (relapsed NHL).

Patients were first treated with two cycles of conventional chemotherapy followed by high-dose sequential chemotherapy and autologous stem cell transplantation. By 100 days post-transplant, 43% of patients had at least a partial reduction in detectable NHL. Survival at two years was significantly higher in patients who had relapsed NHL at the start of the study than in patients who had refractory NHL at the start of the study. Fifty-eight percent of patients with relapsed NHL survived for at least two years after treatment, compared to 24% of patients with refractory NHL.

The researchers conclude that patients with relapsed aggressive NHL may benefit from treatment with high-dose sequential chemotherapy and autologous stem cell transplantation. Among patients with refractory NHL, the results of this treatment regimen were deemed “unsatisfactory”. The researchers are now modifying the treatment regimen used in this study to include Rituxan® (rituximab) for patients with relapsed NHL.​

Reference: Josting A, Sieniawski M, Glossmann J-P et al. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a multicenter phase II study. Annals of Oncology. 2005;16:1359-1365.