High-Dose Therapy with Stem Cell Transplant for Myelodysplastic Syndromes

This content has been reviewed and approved by

Hagop M. Kantarjian, MD
Chairman & Professor, Leukemia Department
MD Anderson Cancer Center
University of Texas

High-doses of chemotherapy are more effective at killing cancer cells than lower doses. However, high-dose therapy destroys many other cells in the body. A dangerous side effect of administering high-dose therapy is damage to the cells in the bone marrow that develop into mature blood cells—called stem cells. 

Without functioning stem cells in the bone marrow, the body cannot produce red blood cells, white blood cells, or platelets. This leaves patients vulnerable to infection and bleeding, and unable to supply adequate oxygen to their tissue. 

However, bone marrow function can be restored after high-dose therapy by replacing the damaged stem cells with healthy ones. This is a procedure known as a stem cell transplant. 

There are two possible sources of stem cells for transplantation: they may be collected from the patient before the start of high-dose therapy or they may be collected from a donor. A stem cell transplant that uses the patient's own cells is called an autologous stem cell transplant. When the stem cells are from a donor, the procedure is called an allogeneic stem cell transplant. 

Currently, the treatment for myelodysplastic syndromes (MDS) that holds the most hope for a cure is high-dose chemotherapy followed by an allogeneic stem cell transplant. 

Long-term survival with high-dose chemotherapy followed by stem cell transplant - In a clinical trial conducted in Europe, patients with MDS or acute leukemia that had developed from MDS were first treated with moderate-dose chemotherapy followed by one round of high-dose chemotherapy. After high-dose chemotherapy, patients underwent either an allogeneic transplant if an appropriate donor was available or an autologous transplant if a donor was not available. Approximately one-third of patients lived 4 years or more after treatment with stem cell transplantation, and approximately the same amount had no evidence of their cancer at 4 years after treatment. 

Myleran® or Busulfex® (busulfan)-containing chemotherapy regimen before stem cell transplant - Researchers from the Fred Hutchinson Cancer Center in Seattle have reported results of a clinical trial that strongly suggest the use of the chemotherapy drug –busulfan--before stem cell transplantation leads to improved outcomes. All patients received high-dose busulfan and cyclophosphamide followed by stem cell transplantation from either related or unrelated donors. Approximately one-third of patients lived 3 years or more after treatment without a relapse of their cancer. Treatment-related deaths occurred in approximately one-third of all patients, and approximately 15 percent had a recurrence of their disease. 

Reduced-intensity chemotherapy followed by stem cell transplantation - Allogeneic stem cell transplants with reduced-intensity chemotherapy are emerging as a very important therapy for patients with blood cancers. 

Researchers have reported that among older patients with myelodysplastic syndrome who were treated with reduced-intensity chemotherapy followed by allogeneic transplant, more than two-thirds lived 2 years or more without a cancer event. 

Strategies to Improve Stem Cell Transplant for MDS 

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. This is accomplished through clinical trials. Future progress in the treatment of MDS with stem cell transplant 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 stem cell transplant for MDS include the following: 

• Autologous stem cell transplant 
• “Mini” transplant 
• Umbilical cord transplant 

Autologous stem cell transplant - An autologous stem cell transplant uses the patients own stem cells, while allogeneic transplants involve the collection of stem cells from a donor. High-dose chemotherapy and autologous stem cell transplant had not been widely used to treat myelodysplastic syndrome because stem cells collected from the patient with myelodysplasia were thought to be abnormal. However, many patients are not able to undergo an allogeneic stem cell transplant because of the side effects of the procedure or the absence of a matched donor. 

Results of a clinical trial have shown that autologous stem cell transplants may provide long-term survival for patients with MDS or AML secondary to MDS.

“Minitransplants” - A minitransplant involves lower doses of therapy before stem cell transplant using donor cells. Minitransplants have been associated with a lower treatment-related mortality than high-dose allogeneic stem cell transplants, while still providing the benefit of donor stem cells that can attack the patient's cancer cells. Minitransplants are being investigated in clinical trials and may prove to be hopeful strategies for elderly patients who may not be able to tolerate the potential complications of a conventional allogeneic stem cell transplantation. 

Umbilical cord transplantation - Umbilical cord transplant may be an effective option for patients with myelodysplastic syndrome who are eligible for an allogeneic stem cell transplant, but cannot find a suitable donor. However, the major disadvantage of using umbilical cord blood is the low number of stem cells collected, which has limited the use of this technique, particularly in larger patients who require more stem cells.