Allogenic Stem Cell Transplant for Chronic Lymphocytic Leukemia
by Dr. C.H. Weaver M.D. updated 7/2016
Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL) is considered a very indolent or slowly growing cancer, occurring predominantly in older individuals. Because the cancer grows slowly, it is very hard to cure with traditional cancer chemotherapy or radiation therapy treatments, which only destroy rapidly growing cells. Although curing patients is very difficult, patients may live a very long time with their disease. In fact, the average patient with SLL/CLL lives 6-10 years from diagnosis.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of SLL/CLL with allogeneic stem cell transplantation. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
For patients under the age of 50-60 with SLL/CLL, allogeneic stem cell transplantation may be a treatment option. For a general overview of the process of allogeneic stem cell transplant, select allogeneic stem cell transplant.
Allogeneic Stem Cell Transplantation for SLL/CLL
Allogeneic stem cell transplantation is the only therapeutic strategy that is potentially curative for patients with SLL/CLL. Until ten years ago, SLL/CLL had been considered an incurable slowly growing cancer of the elderly requiring chemotherapy only to treat symptoms or delay disease progression. In parallel with the growing evidence of safety and effectiveness of stem cell transplantation for the treatment of other leukemias, there was emerging interest in using this approach to treat younger patients with SLL/CLL. About 40% of patients with SLL/CLL are younger than 60 years and about 10% are younger than 50 years at the time of the diagnosis.
In spite of several new drugs and new drug combinations, or precision cancer medicines, there is no current evidence that any of these strategies can cure patients with SLL/CLL. The average duration of survival for younger patients with SLL/CLL remains around 5 years from the initiation of therapy. The most useful predictor for decreased survival is the history of prior treatment. Patients with SLL/CLL who fail any kind of therapy (cancer returns or progresses after treatment) have an average life expectancy of 30 months. Patients who are refractory to treatment with chemotherapy have an average survival of only 9 months. These outcomes have resulted in consideration of more aggressive and potentially curative approaches, such as stem cell transplantation. Two transplantation strategies have been evaluated for patients with SLL/CLL: autologous stem cell transplantation and allogeneic stem cell transplantation. For more information on autologous transplantation, go to autologous stem cell transplant.
Allogeneic stem cell transplantation has two main advantages. One advantage is that the stem cells collected from a donor are free of leukemia. The other advantage is that the donor lymphocytes facilitate the killing of SLL/CLL cells by an immunologic graft-versus-leukemia effect. These two features of an allogeneic stem cell transplant act in concert with high doses of chemotherapy and irradiation to contribute to the cure of some patients with SLL/CLL.
Several hundred patients with SLL/CLL have received allogeneic bone marrow or blood stem cell transplants. The main disadvantage of an allogeneic stem cell transplant is the side effects, which may result in death in up to 20% of patients although those continues to improve. This is mainly due to complications related to graft-versus-host disease. Leukemia recurrence is unusual and 45-65% or patients survive beyond 3 years from treatment and may be cured.
Strategies to Improve Treatment with Allogeneic Stem Cell Transplantation
Increase in the use of Donors other than HLA-Matched Siblings: Since only a quarter of patients will have an HLA-matched family member donor, there is much ongoing research aimed at increasing the number of available donors. There has been significant progress in the use of partially matched family member donors, especially in children. Currently, an HLA-compatible unrelated donor can be found for approximately 70% of patients; however, the search must be initiated early enough in the disease course to be of benefit. There is also increasing definition of the degree of mismatching that can be tolerated in unrelated donors, especially in children. The use of umbilical cord blood is expanding and will increase the unrelated donor pool. Until recently, umbilical cord blood transplants have been restricted to children. Recent clinical studies suggest that umbilical cord blood can be expanded in culture and used successfully in adults.
“Mini-transplants”: Traditionally, the high-dose radiation and chemotherapy regimens used in allogeneic stem cell transplants are very toxic and involve complete destruction of the bone marrow. Recently, several transplant centers have evaluated less toxic regimens, including lower doses of chemotherapy, radiation and/or biologic therapy prior to an allogeneic transplant. The concept of a mini-transplant is two-fold. The less toxic regimens utilizing lower doses of chemotherapy, radiation therapy and/or biologic therapy kill some cancer cells and suppress the patient’s immune system so that it won’t attack the donor cells. Once the donor cells are infused into the patient, they can recognize the patient’s cancer cells as foreign and mount an attack against the cancer.
Several small clinical trials have demonstrated that successful eradication of leukemia cells can be achieved with (“mini-transplants”). This represents a potential new approach for safer treatment of a large variety of cancers currently treated with allogeneic stem cell transplantation, including multiple myeloma. The technique of mini-transplants has now been expanded to include the use of unrelated HLA-matched donors and has the potential to make this therapy more widely applicable. This is important for elderly patients, as their age often excludes them from being able to receive the high dose of treatment typically used in allogeneic stem cell transplantation.
Monoclonal Antibodies: Another approach is to deliver additional treatment directed specifically to the leukemia cells and avoid harming the normal cells. This is an attractive approach since there are now a variety of monoclonal antibodies that are specific for B cell lymphomas and leukemias. Some antibodies will kill lymphoma cells directly like Rituxan® or are linked to toxins or radioactive isotopes that kill cancer cells.