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 tissues.
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 prior to undergoing high-dose therapy or they may be collected from a donor. A stem cell transplant that utilizes 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 MDS that holds the most hope for 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 four years or more after treatment with stem cell transplantation, and approximately the same amount had no evidence of their cancer at four years after treatment. 
Busulfan-containing chemotherapy regimen prior to stem cell transplant: Researchers from the Fred Hutchinson Cancer Center in Seattle , Washington , have reported results of a clinical trial that strongly suggest the use of the chemotherapy drug busulfan prior to 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% 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 from England 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 two years or more without a cancer event. 
To learn more, go to Allogeneic Stem Cell Transplant.
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 utilizes 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 due to 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. Patients involved in this trial were first treated with initial moderate-dose chemotherapy followed by one round of high-dose chemotherapy. After high-dose chemotherapy, patients with a matched donor were treated with an allogeneic transplant, and those with no matched donor were treated with an autologous transplant.
The number of patients who were cancer-free four years after transplant was similar for both types of transplant—27% for autologous and 31% for allogeneic. Patients who experienced a complete remission during therapy and received their transplant while in remission had slightly better outcomes, but there was still little difference between autologous and allogeneic transplant. 
“Mini transplants”: A mini transplant involves lower doses of therapy prior to stem cell transplant using donor cells. Mini-transplants 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. Mini-transplants are being investigated in clinical trials involving various cancers 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.
Researchers from Germany have reported that “mini” allogeneic stem cell transplants may provide a chance for cure for patients over 60 years of age with poor-prognosis blood cancers, including MDS. Of the 19 patients involved in this study, 17 experienced a complete disappearance (complete remission) of their cancer. Also, 13 patients lived nearly two and a half years after treatment. 
Umbilical cord transplantation: Results from a clinical trial conducted in Japan suggests that an 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. 
To learn more about treatment techniques that are being evaluated in clinical trials, go to Strategies to Improve Treatment of MDS.
 Theo de Witte T, Suciu S, Verhoef G, et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood. 2001; 98(8):2326-2331.
 Deeg H, Storer B, Slattery J, et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood. 2002;100:1201-1207.
Taussig DC , Davies AJ, Cavenagh JD, et al. Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia after Reduced-Intensity Allografting. Journal of Clinical Oncology. 2003;21:3060-3066.
 de Witte T, Suciu A, Verhoef S, et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood. 2001;98:2326-2331.
 Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. Journal of Clinical Oncology. 2003;21:1480-1484.
 Ooi J, Iseki T, Takahashi S, et al. Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. Blood. 2003 Jun 15;101(12):4711-3.