Certain types of lymphoma have been difficult to cure with standard autologous stem cell transplant. Researchers have evalauated allogeneic stem cell transplantation and more recently CAR T Cell therapy as an alternative to ASCT.
In an allogeneic stem cell transplant, high doses of chemotherapy and/or radiation therapy are used to kill more cancer cells than standard doses. The high doses of therapy tend to result in severe side effects, including low levels of hematopoietic stem cells (immature blood cells). Low levels of these stem cells can result in life-threatening complications, such as infection, bleeding, or anemia. In order to combat this side effect, stem cells are collected from a donor and infused into the patient following the high-dose therapy. The stem cells mature into functioning blood cells to restore low levels and reduce associated side effects.
An added benefit of an allogeneic stem cell transplant (stem cells from a donor) is that the donor’s stem cells recognize the patient’s cancer cells as “foreign” and mount an attack against them.
Anaplastic Large Cell Lymphoma
Anaplastic large cell NHL is considered an aggressive type of NHL. Patients with anaplastic large cell NHL that has recurred following prior therapies are unlikely to be cured with further chemotherapy or an autologous stem cell transplant. Researchers are evaluating aggressive treatment approaches, such as allogeneic stem cell transplantation, for this group of patients in an attempt to improve long-term survival.
Researchers from Germany conducted a clinical trial to evaluate the effectiveness of an allogeneic stem cell transplant in children or adolescents with anaplastic large cell NHL that had stopped responding to standard therapies. This trial included 20 patients who were treated with a transplant between 1991 and 2003, from either related or unrelated donors. Nine patients had experienced their first cancer relapse prior to the allogeneic transplant, and 11 patients had experienced several cancer relapses prior to the transplant.
Allogeneic stem cell transplantation appeared effective in this group of patients:
- At 3 years following therapy, 75% of patients were alive without cancer progression.
- The five patients who had received a prior autologous transplant (procedure in which the patient’s own stem cells are collected prior to high-dose therapy and re-infused following therapy) were all alive and cancer-free.
- Two patients died of recurrent disease.
- Three patients died from treatment-related causes.
The researchers concluded that allogeneic stem cell transplantation results in long-term survival for a large fraction of children or adolescents with anaplastic large cell NHL that has stopped responding to prior therapies.
Understanding DNA Damage Response or DDR and Cancer Treatment
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Angioimmunoblastic T Cell Lymphoma (AITL)
Among patients with a type of T-cell non-Hodgkin’s lymphoma known as angioimmunoblastic T-cell lymphoma (AITL), treatment with allogeneic stem cell transplantation results in long-term disease-free survival in approximately 50% of patients.
T-cell lymphomas are a relatively uncommon form of non-Hodgkin’s lymphoma (NHL) that generally do not respond as well to treatment as B-cell NHL. AITL is considered a subtype of peripheral T-cell lymphoma (PTCL). Symptoms may include high fever, night sweats, weight loss, and skin rash. The disease is more common in males, and the median age at diagnosis is 65 years. Patients with AITL are often diagnosed at an advanced stage of the disease and are considered candidates for stem cell transplantation.
Autologous stem cell transplants (stem cell transplants that utilize the patient’s own stem cells) have been used as upfront therapy for patients with AITL, with 48% of patients remaining free of cancer progression at three years. Allogeneic stem cell transplants (stem cell transplants that utilize donor stem cells) have also been effective for PTCL patients who have failed chemotherapy.
To evaluate allogeneic stem cell transplantation in patients with AITL, researchers conducted a study among 45 patients. Thirty-four of the patients had already received two or more treatment regimens and 11 had experienced cancer progression following an autologous stem cell transplant.
- Three-year survival without cancer progression was 54%.
- Three-year overall survival was 64%.
- Treatment-related mortality was 25%.
20% of patients experienced a relapse during the first three years after treatment. Relapse rates were lower among patients who experienced chronic graft-versus-host disease and among patients who were not resistant to chemotherapy.
The results of this study suggest that a significant fraction of patients with AITL who fail conventional chemotherapy will respond to an allogeneic stem cell transplant. This study also suggests that patients should receive an allogeneic stem cell transplant before the development of chemotherapy resistance.
- Woessmann W, Peters C, Lenhard M, et al. Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents –a Berlin-Frankfort-Munster group report. British Journal of Haematology. 2006;133:176-182.
- Kyriakou C, Canals C, Finke J, et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: A retrospective study from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Journal of Clinical Oncology [early online publication]. July 20, 2009.