PHILADELPHIA INTERNATIONAL MEDICINE NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
March 21, 2003

For Immediate Release:

In this month's edition of the PIM News Bureau:

1. "Mini-Transplants" Offer New Hope for Older Cancer Patients

2. Cardiac Resynchronization: Crozer-Chester Medical Center Offers Heart Failure Patients a New Therapy

3. CHOP Study Shows Children with Heart Defects Benefited from Milrinone After Surgery

PHILADELPHIA - Philadelphia International Medicine hospitals and physicians are finding new ways to bring the highest quality care to patients of all ages. In this month's PIM News Bureau, we bring three examples of newer programs geared to seniors, children and all ages.

"Mini-Transplants" Offer New Hope for Older Cancer Patients

Patients in their 50s and 60s with blood malignancies, such as leukemia and lymphoma, traditionally have not been eligible for bone marrow or stem cell transplants. Now, new advances allow Fox Chase-Temple's Bone Marrow Transplant (BMT) Program to offer these patients "mini-transplants," a less toxic, and often more successful procedure than traditional bone marrow transplants for treating blood cancers.

Fox Chase Cancer Center and Temple University Hospital are both members of the Philadelphia International Medicine network.

"Because mini-transplants are much less toxic than traditional transplants, we're able to offer this procedure to older patients (up to age 70), even when they have other underlying medical complications," said Kenneth F. Mangan, MD, director of the Fox Chase-Temple BMT Program.

A traditional allogeneic (use of stem cells from related and unrelated donors) bone marrow transplantation requires the patient to receive high doses of radiation and chemotherapy, which destroys the bone marrow, the cancer in the bone marrow, and the immune system. A new immune system is created with the transplanted donor stem cells.

"For a mini-transplant, the patient receives low doses of radiation or chemotherapy, which suppresses, but doesn't destroy the immune system," explained Mangan. "This allows us to transplant either matched-related or unrelated stem cells. The goal is to create a new, cancer-free immune system that allows patients to fight the cancer. The donor cells actually attack the malignant cells."

A mini-transplant is performed as an inpatient procedure with significantly fewer side-effects and shorter hospitalization than a traditional allogeneic stem cell transplant.

"We've had amazing successes over the last four years with mini-transplants," Mangan said. "We regularly see continuous, complete remissions when using a mini to treat most forms of blood cancers. Many patients with relapsed non-Hodgkin's and Hodgkin's lymphomas are also benefiting, as are patients with mantle cell lymphoma, a previously incurable malignancy."

Other cancers currently being treated with mini-transplants include chronic myelogenous leukemia, myelodysplastic syndromes, chronic lymphocytic leukemia, auto myelogenous leukemia, multiple myeloma, follicular (low grade) lymphomas, and large cell lymphomas.

Cardiac Resynchronization: Crozer-Chester Medical Center Offers Heart Failure Patients a New Therapy

A bout with pneumonia in 1992 did more damage to Linda Artymowicz's heart than anyone could imagine. The viral infection that began within her lungs ended up damaging her heart muscle, as well as the electrical system of her heart, leaving her with irreversible heart failure.

Although not a specific disease, heart failure describes a serious condition where the heart's chambers "fail" to work adequately to maintain a sufficient flow of blood to supply the body's needs. Heart failure can be caused by a heart attack, clogged blood vessels, high blood pressure, diabetes, or, as in Artymowicz's case - damage caused by an infection. Patients with heart failure most often describe the symptoms of heart failure - exhaustion, shortness of breath and cold fingers and toes - as living while slowly dying.

It was Artymowicz's good fortune that her care was being provided by Scott Hessen, MD, medical director, elecrophysiology laboratory. Crozer-Chester Medical Center offers a unique device therapy called biventricular resynchronization.

As an electrophysiologist, Hessen is a cardiologist who completed special training in diagnosing and treating heart rhythm disorders. Because of his training, Hessen was familiar with the device therapy that takes a traditional pacemaker or implantable defibrillator one step further - a third lead.

"Six months ago, we did not have the option of device therapy to offer our heart failure patients," says Hessen. This device simultaneously paces both sides of the heart and the resulting resynchronization helps improve the heart' s pumping efficiency. Although biventricular resynchronization cannot reverse the damage done to the heart, it can help to alleviate the most troublesome symptoms of heart failure.

"Nationwide, we have seen the death rate from coronary artery disease and other heart conditions go down while deaths from heart failure continue to rise," says R. David Mishalove, MD, chief of cardiology at Crozer-Chester Medical Center. We can only expect a bigger problem with heart disease as the population ages."

According to Hessen, biventricular resynchronization is not for all heart failure patients. "About one out of every three heart failure patients will benefit and it can make a remarkable difference in their lives. In the normal heart, its electrical conduction system delivers impulses uniformly to keep the chambers pumping in sync," says Hessen.

"The impulses coordinate how the heart muscle contracts and pumps blood. If the electrical pathways are damaged, the heart muscle cannot pump blood efficiently throughout the circulatory system." This device paces both ventricles simultaneously to resynchronize the heart's muscle contractions. The heart's efficiency is therefore improved.

The biventricular resynchronization device is similar in size, shape and weight as a pacemaker or implantable cardioverter defibrillator. It also uses a battery sealed within to provide necessary electrical impulses to keep the heart's pace synchronized. But its distinctive feature is that it has three leads. One lead is placed into the right atrium, and one is placed into the right ventricle. The third lead is used to pace the left ventricle.

Working in the cardiac electrophysiology lab and under sterile conditions, Hessen uses contrast dye to help map out the veins that lead to the heart. Since the left ventricle is the heart's main pumping chamber, Hessen snakes the third lead though the coronary sinus, the main vein of the heart.

Once in the chamber, the third lead is positioned as far from the right ventricle as possible. Once in place, Hessen measures the appropriate pulse needed within the leads to pace the heart. The procedure usually takes two to three hours and patients are usually discharged the next day with minimal discomfort. "This device therapy can greatly improve the quality of life for appropriate heart failure patients," says Hessen. "It is very gratifying to be able to offer it to my patients."

CHOP Study Shows Children with Heart Defects Benefited from Milrinone After Surgery

Infants and young children with heart defects benefited from a drug they received shortly after cardiac surgery. The drug, milrinone, significantly reduced the risk of low cardiac output syndrome (LCOS), a life-threatening reduction in the heart's pumping ability.

The study, involving 238 patients at 31 hospitals in the United States and Canada, was the largest randomized trial in children following heart surgery. Researchers from the Cardiac Center at The Children's Hospital of Philadelphia led the study, which appeared in the Feb. 25 issue of Circulation, the official journal of the American Heart Association. The Children's Hospital of Philadelphia is Philadelphia International Medicine's pediatric provider.

Nearly one of every 100 children is born with a heart defect, of which more than one-third will require surgery. The children in this study all had heart conditions that required corrective open-heart surgery undercardiopulmonary bypass, usually within their first year of life.

The patients were randomly divided into three groups: one receiving a low dose of milrinone, one receiving a high dose, and a group that received a placebo. During the critical first 36 hours after surgery, the high-dose group was 55 percent less likely to suffer LCOS compared to the placebo group.

"This provides hard evidence for using this drug in children," said co-principal investigator Gil Wernovsky, MD, medical director of the Cardiac Intensive Care Unit at Children's Hospital. Milrinone improves the heart's ability to squeeze and relax, as well as lowering blood pressure in blood vessels. It has been used to treat adults with acute heart failure, and has previously been used to treat children after they had developed LCOS following heart surgery.

The current study, called PRIMACORP for prophylactic intravenous use of milrinone after cardiac operation in pediatrics, was the first to investigate use of the drug before LCOS symptoms developed. "This trial was a genuine partnership between industry and academic medicine," said Wernovsky. Sanofi-Synthelabo Inc., which manufactures milrinone, sponsored the study at 31 medical centers. "It was particularly important that milrinone's side effects and efficacy were fully tested in children in a large, placebo-controlled trial. Many drugs used for children have never been thoroughly tested in children, and we can't assume that children are just small adults."

He added that data from this trial can be further analyzed for pharmacokinetics - how children's bodies process the drug - which may be different from the results in adults.

Side effects of milrinone that have been reported in adults, such as low blood pressure, blood platelet abnormalities, and irregular heart rhythms, occurred infrequently in the children studied, and were not more common in patients receiving milrinone compared to those who received a placebo.

"Although this trial did not directly study other benefits such as shorter hospitalizations and fewer postoperative complications, we believe that these benefits may result from reducing low cardiac output," said co-principal investigator Timothy M. Hoffman, MD. "Those questions need to be pursued in future research.

"Wernovsky and Hoffman submitted the study from the Cardiac Center at The Children's Hospital of Philadelphia, as did a third co-author, Thomas L. Spray, MD, chief of the Division of Cardiothoracic Surgery. (Hoffman is currently at Ohio State University.) The Cardiac Center is a comprehensive center for the care of infants, children and young adults with congenital and acquired heart disease. Other co-authors represented pediatric cardiology programs at six other hospitals.

Philadelphia International Medicine is an organization that provides medical and patient support services to international patients. It also provides continuing medical education and health care training and education to international physicians, administrators and other practitioners. As the international department of several Philadelphia-area hospitals, international patients gain access to physicians and hospitals rated among the best in the world through one telephone call to PIM. You can reach PIM by calling 1-215-735-3575; fax, 1-215-790-1267; or e-mail, physicians@philadelphiamedicine.com.  You can find out more about PIM through its Website at www.philadelphiamedicine.com.