In order to better understand which patients are likely to require readmission and which are not, Dr. Roland Walter, from the Fred Hutchinson Cancer Research Center and lead author of the study, said, “A larger study, such as the one we have now initiated and that is open for accrual, might help to find parameters that predict who is very likely to be readmitted after one or two days.  Down the road, such patients would probably be excluded from attempts to discharge early after completion of chemotherapy.”

Patients with high-risk myelodysplastic syndromes (MDS) typically undergo intensive chemotherapy to achieve disease remission and then remain in the hospital for three to four weeks until their blood counts recover, so they can be treated for infection and bleeding complications.

Improved preventative medications and outpatient support has allowed a shift to outpatient care after many blood disease treatments, including transplantation.  In these cases, outpatient care is preferable because costs are reduced, quality of life is better, and the risk of hospital-acquired infection decreases.

“There is a concern that patients discharged early could have a complication (potentially fatal) because the access to medical care is delayed until they reach the clinic or hospital. On the other hand, there is equal concern that the hospital environment may actually be harmful for the patient because they are more likely to get a [hospital-acquired] infection (these are often hard to treat and can be deadly),” Dr. Walter wrote in an e-mail to The Beacon.

Based on the success of outpatient care following other treatments, researchers conducted a study of the safety and cost of discharging patients immediately following chemotherapy for treatment of high-risk MDS and acute myeloid leukemia (AML).

“While only 3 patients in our study had high-risk MDS, we believe that the data should be applicable to MDS patients who receive AML-like induction chemotherapy. We believe that it is primarily the type and intensity of treatment that dictates the rate of complications,” said Dr. Walter.

In this study, fifteen patients were discharged immediately after chemotherapy and five remained hospitalized.

The inpatient group tended to need extended antibiotic treatment (16 days) compared with the outpatient group (six days).  In addition, the inpatient group generally required more red blood cell transfusions than the outpatient group.

Of the 15 patients who were discharged, seven were readmitted once and six were readmitted twice during the study due to fever, bleeding, or nausea.  They were then discharged once the complication was alleviated.  During the study, the group of discharged patients spent 54 percent of the time as outpatients.

The researchers also evaluated the cost of care of patients in the study.  On average, the cost per day was significantly reduced for patients who were discharged ($3,270) compared with hospitalized patients ($5,467).

“I don’t think we should use finances as the primary driver for this treatment strategy, but cost savings could be substantial,” added Dr. Walter.

For additional information, please see the article in Haematologica (pdf) or the clinical trial information for the current follow-up study.

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).

Acute pulmonary failure is a rare but serious complication of chemotherapy.  The condition is characterized by lung injury and respiratory distress, and it is unrelated to heart failure.

MDS patients receive chemotherapy drugs to kill cancerous cells, help bone marrow to produce healthy blood cells, and prepare for bone marrow transplantation.  Intensive treatments usually range from six to nine months, and bring short-term reduction of symptoms for as high as 60 percent of MDS patients.

Researchers reviewed 1541 newly diagnosed AML and High-risk MDS patients undergoing intensive chemotherapy.  High-risk MDS patients had greater than 10 percent blasts, which are mass groupings of cells. AML patients showed greater than 20 percent blasts.

Patients requiring mechanical ventilatory support in the intensive care unit within two weeks of the initiation of chemotherapy regimen were categorized as having acute pulmonary failure.

The study did not distinguish AML from MDS patients.  Results showed that 8 percent developed acute pulmonary failure, 30 percent did not respond to treatment, and 14 percent died within six weeks of beginning chemotherapy.  These effects were similar for AML and High-risk MDS patients.

Fifty-five percent achieved complete response, as defined by the 2000 International Working Group criteria as having a blood count of more than 1,000 neutrophil per mL (type of white blood cell) and more than 100,000 platelets per mL (growth cells).

The median duration of complete response for all patients after starting chemotherapy was eight months.  Patients who developed acute pulmonary failure survived a median of three weeks, while those who did not experience lung failure survived for a median of 15 months.

There are no definite factors for predicting acute pulmonary failure; course and prognosis of the condition are not well understood.  In addition, it is often difficult to discern the most important cause when there are multiple contributing factors.

This study revealed pre-existing conditions that may predispose AML and High-risk MDS patients for lung failure.  These include being male, having acute promyelocytic leukemia, not responding well to chemotherapy, and the presence of lung infiltrate at diagnosis.

Although the causes of acute pulmonary failure cannot be identified and prevented completely, MDS patients can be monitored for signs of predisposing factors.  The authors suggest supportive care is important, such as platelet support for High-risk patients, restriction of fluids, and other methods to reduce the probability of unnecessary bleeding.

Such strategies can increase the tolerance of high-intensity chemotherapy and ultimately increase long-term outcomes of High-risk MDS patients.

For more information, please see the journal Cancer (full text).