The MDS Beacon™

The treatment options for myelodysplastic syndromes (MDS) patients represents a continuing discovery process with different levels of intensity as evaluated in a recent review of treatment options published in the supplement of the journal Cancer Control.

The main goals when treating high-risk MDS patients are to increase overall survival and delay progression to acute myeloid leukemia (AML). Researchers also strive to improve quality of life through supportive care, achieve independence from red blood cell transfusions, and decrease symptoms.

Options for high-risk MDS patients are divided into high-intensity therapies, including stem cell transplantation and standard chemotherapy, and low-intensity treatments, such as reduced-intensity chemotherapy and drug therapies such as Vidaza (azacitidine) and Dacogen (decitabine). 

In the U.S., 29 percent of MDS cases are classified as high-risk disease at diagnosis according to the International Prognostic Scoring System (IPSS). 

The IPSS score predicts median survival and expected progress to AML if patients do not receive treatment.  It is determined by evaluating the percent of immature blood stem cells, blood cell counts, and genetic structure at the time of diagnosis. The World Prognostic Scoring System (WPSS) also predicts prognoses, but evaluates patients as their disease progresses.

This article describes the different levels of treatment as evaluated by the authors of the review.

High-Intensity Therapies

Stem cell transplantation is the only curative option for high-risk MDS patients. In this treatment, the bone marrow of a patient is initially destroyed by high-dose chemotherapy or radiation, and then replaced with bone marrow from a matched donor. Although not guaranteed to produce a full recovery, stem cell transplants give the patient new bone marrow to produce normal blood cells. 

Studies have shown that stem cell transplantation soon after diagnosis maximizes the average survival for high-risk patients. In addition, age alone is no longer a deterrent for transplantation.

Other studies have shown that although increasing age, longer duration of disease, mismatched donor, and being male significantly increase non-relapse mortality after stem cell transplantation, they do not affect disease-free survival in MDS patients.

The authors of the review point out that research has not yet shown if previous treatment before transplantation with DNA demethylating agents, such as Vidaza or Dacogen, or remission-inducing chemotherapy improves transplantation success.

Reduced-Intensity Therapies

MDS patients who are older, have higher-risk disease, or have other concurrent health conditions and therefore would not be candidates for stem cell transplantation can choose to have reduced-intensity chemotherapy before stem cell transplantation. Reduced-intensity chemotherapy would allow them to have stem cell transplantation because it is associated with fewer complications and side effects.

Although patients receiving reduced-intensity therapy before stem cell transplantation have increased relapse rates after transplant, they tend to have decreased mortality if relapse does not occur. In addition, overall survival and progression-free survival is similar to patients receiving standard, high-intensity chemotherapy. 

The authors of the review point out that optimal timing and overall effectiveness of reduced-intensity therapy has not yet been established.

Low-Intensity Therapies

Vidaza and Dacogen are considered low-intensity therapies for high-risk MDS patients. Both drugs are DNA demethylating agents that remove methyl groups bound to the DNA in the bone marrow in order to allow the DNA to regulate normal cell growth.

Vidaza is one commonly used drug therapy for high-risk MDS patients. It has been shown to significantly increase survival time, slow progression to AML, produce red blood cell transfusion independence, and improve blood counts and quality of life compared to conventional care and chemotherapy. 

Although Vidaza does not guarantee complete response, the significantly higher survival rates show that complete response to therapies is not necessarily required to increase patient survival time. 

High-risk MDS patients receiving Dacogen also have significantly higher rates of complete response, partial response, and blood counts than those receiving best supportive care. They also have longer periods of survival that are free of disease progression to AML.

However, median survival and overall progression to AML is similar between the patients receiving Dacogen or supportive care.

The authors of the review point out that high-risk patients who do not respond to any of the existing therapies can choose to participate in clinical trials that investigate new treatment options. 

For more information, please see the article in the supplement of Cancer Control (pdf).