ASCT for Hodgkin's Lymphoma

Autologous stem cell transplant (ASCT) plays an integral role in the treatment of patients with Hodgkin’s lymphoma. Most patients with Hodgkin’s lymphoma are cured with combination chemotherapy with or without radiation therapy. ASCT is currently the optimal treatment for patients who fail chemotherapy and radiation therapy. For a general overview of the process of ASCT, select Autologous Stem Cell Transplant .

The following is a general overview of ASCT in the treatment of Hodgkin’s lymphoma. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied. The potential benefits of multi-modality care, participation in a clinical trial or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

ASCT as Consolidation Therapy in First Complete Remission for High-Risk Patients

While results from a few clinical trials suggest that patients with Hodgkin’s lymphoma who are at high-risk of relapse may benefit from an early ASCT during their first complete remission, a 2003 study has failed to confirm this observation. This randomized clinical trial was conducted by the European Bone Marrow Transplant Group (EBMT) and involved 163 patients with Hodgkin’s lymphoma who had achieved a remission after initial therapy. The patients were randomly assigned to receive an ASCT or continued chemotherapy. Overall, 94 percent of patients treated with ASCT survived five years without cancer recurrence, compared to 88 percent of those treated with chemotherapy.[1]

ASCT for Patients who Fail Remission Induction

Patients who do not obtain a remission after chemotherapy for Hodgkin’s lymphoma are treated with second-line chemotherapy, which is often followed by an ASCT. In the treatment of these patients, the timing of ASCT is important and should not be delayed. Researchers affiliated with the EBMT have reviewed the outcomes of 175 patients with Hodgkin’s lymphoma who did not enter a remission after initial chemotherapy and were treated with an ASCT. Overall, 36 percent of these patients treated with ASCT survived five years or longer. Patients experienced significantly worse outcomes if the transplant was delayed beyond 18 months after initial treatment. These findings suggest that high-dose chemotherapy and ASCT should be applied as soon as possible once it is determined that initial chemotherapy has not produced a remission.[2]

More recent results using peripheral blood stem cells rather than bone marrow to support an ASCT have shown improved results over those reported by the EBMT. In a study reported by doctors from the Memorial Sloan Kettering Cancer Center, researchers reported that half of 75 consecutive patients with biopsy-confirmed primary refractory Hodgkin’s lymphoma treated with high-dose chemoradiotherapy and ASCT survived 10 years and appeared cured.[3]

ASCT in First Relapse after Achieving an Initial Complete Remission

For patients whose cancer returns, or relapses, after they have been in an initial complete remission, clinical trials show that treatment with high-dose chemotherapy and ASCT results in longer survival than treatment with conventional chemotherapy. The best results in all studies are for patients transplanted soon after first relapse and before the development of refractory disease. When stem cells from peripheral blood are used for support, over 60 percent of patients who are treated with high-dose chemotherapy and ASCT appear cured of their disease.[4] However, it is estimated that only 10 percent to 20 percent of patients in the U.S. with relapsed Hodgkin’s lymphoma receive the benefit of an ASCT, which is typically only performed after multiple failures of chemotherapy. In order to achieve the best results, it is important to discuss ASCT as a treatment option as soon as a recurrence occurs.

ASCT for Patients with Relapsed or Refractory Disease

Although clinical trials have demonstrated that over 60 percent of patients with Hodgkin’s lymphoma can be cured if ASCT is used to treat the disease immediately at the time of recurrence, many patients will not receive treatment at that time. The use of ASCT immediately at the time of initial cancer recurrence is associated with fewer side effects and the best chance of cure. However, ASCT can still be an effective treatment for patients with refractory disease. The results of large clinical trials demonstrate that patients treated with ASCT experience better long-term outcomes compared to conventional chemotherapy. Furthermore, approximately one third of patients can still be cured of their disease.[4],[5]

Strategies to Improve Autologous Stem Cell Transplant

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Hodgkin’s lymphoma will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of Hodgkin’s lymphoma include the following:

Increased dose intensity of the high-dose chemotherapy preparative regimen: Since more treatment typically kills more cancer cells, increasing the intensity of treatment delivered can be accomplished by utilizing higher doses of anti-cancer therapies or by delivering more than one cycle of high-dose chemotherapy treatment prior to ASCT. While increasing the intensity of treatment may kill more cancer cells, this approach may also cause more damage to normal cells and increase side effects. However, one small clinical trial reported by the Southwest Oncology Study Group has suggested that more intensive regimens may improve survival of patients with relapsed Hodgkin’s lymphoma.[6]

Targeted therapy: A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Monoclonal antibodies are a type of targeted therapy that can locate cancer cells and kill them directly or stimulate the immune system to attack them. There are currently no FDA-approved targeted therapies for Hodgkin’s lymphoma. However, German and American researchers have recently reported promising outcomes of a new monoclonal antibody (H22xKi-4) that is being investigated for the treatment of Hodgkin’s lymphoma.[7] This antibody targets the CD30 antigen, or protein, which is present in many Hodgkin lymphoma cells.

Rituxan® (rituximab) was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin’s lymphomas, which have the CD20 antigen on their surface. There is evidence that some patients with Hodgkin’s lymphoma have cancer cells that are susceptible to treatment with Rituxan. The results of small clinical trials suggest the Rituxan can cause remissions in some patients with Hodgkin’s lymphoma.[8],[9]

Minimal residual disease: Following treatment with high-dose chemotherapy, more patients achieve a complete remission (complete disappearance of their cancer) than those treated with conventional doses. Unfortunately, many patients in remission still experience a relapse of their cancer. This is because not all of the cancer cells were destroyed. Doctors refer to this as a state of "minimal residual disease.” Many doctors believe that the best approach to eradicating these cancer cells and preventing the cancer from returning is to deliver additional cancer treatments during the post-transplant recovery period when only a few cancer cells remain.

Maintenance chemotherapy: The administration of relatively low doses of chemotherapeutic drugs after an autologous transplant could delay time to progression or prevent relapses. New drugs are constantly being evaluated in the conventional treatment of patients with lymphoma and could be used after high-dose chemotherapy with autologous stem cell support.

References


[1] Bellei FM, Brice P, Brugiatelli M, et al. High-Dose Therapy and Autologous Stem-Cell Transplantation Versus Conventional Therapy for Patients with Advanced Hodgkin;s Lymphoma Responding to Front-Line Therapy. Journal of Clinical Oncology. 2003;29:555-559.

[2] Sweetenham JW, Carella AM, Taghipour G, et al. High-Dose Therapy and Autologous Stem-Cell Transplantation for Adult Patients with Hodgkin’s Disease who do not enter Remission after Induction Chemotherapy: Results in 175 Patients treated between 1979 and 1995 and reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. Journal of Clinical Oncology. 1999;17:3101-3109.

[3] Moskowitz CH, Kewalramani T, Nimer SD, et al. Effectiveness of high dose chemoradiotherapy and autologous stem cell transplantation for patients with biopsy-proven primary refractory Hodgkin's disease. British Journal of Hematology. 2004;124:645-652.

[4] Tarella C, Cuttica A, Vitolo U, et al. High-Dose Sequential Chemotherapy and Peripheral Blood Progenitor Cell Autografting in Patients with Refractory and/or Recurrent Hodgkin Lymphoma. A Multicenter Study of the Intergruppo Italiano Linformi Showing Prolonged Disease Free Survival in Patients Treated at First Recurrence. Cancer. 2003;97:2748-2759.

[5] Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: A randomised trial. Lancet. 2002;359: 2065-2071.

[6] Stiff PJ, Unger JM, Forman S, et al. The Value of Augmented Preparative Regimens Combined with an Autologous Bone Marrow Transplant for the Management of Relapsed or Refractory Hodgkin disease: A Southwest Oncology Group Phase II Trial. Biol Blood Marrow Transplant. 2003;9:529-39.

[7] Borchmann P, Schnell R, Irene Fuss I, et al. Phase 1 trial of the novel bispecific molecule H22xKi-4 in patients with refractory Hodgkin lymphoma. Blood. 2002,100:3101-3107.

[8] Younes A, Romaguera J, Hagemeister F, et al. A Pilot Study of Rituximab in Patients with Recurrent, Classic Hodgkin Disease. Cancer. 2003;98:310-314.

[9] Ibom VK, Prosnitz RG, Gong JZ, et al. Rituximab in lymphocyte predominance Hodgkin's disease: a case series. Clinical Lymphoma. 2003;4:115-118.