Most cancer patients receive one or more of the following therapies: chemotherapy, radiation therapy, and hormone therapy. These treatments are used to target and kill cancer cells. In some cases, the therapy treats the cancer directly; in other cases, it is administered to prepare the patient for a stem cell or bone marrow transplant, which is another method used to treat cancer or other disease. While therapies are designed to kill off the cancer cells, they can unfortunately carry significant negative side effects, including damage to the cells that line the blood vessel walls, which can lead to various disorders of the vascular system. So much damage, in fact, that some patients may not be able to continue with cancer treatments because they develop these vascular system complications. Other patients believed to be at high risks for developing these vascular system complications may not receive optimal cancer treatments or any treatment at all due to these complications.
Veno Occlusive Disease (“VOD”) is a disorder of the vascular system that can result from commonly used cancer therapies such as chemotherapy, radiation therapy and hormone therapy. Specifically, the aggressive pre-conditioning regimen that precedes stem-cell transplantation can expose a patient to high levels of various chemotherapies, which travel to the microvessels of the liver with the intent of being filtered out though circulation. These microvessels in turn experience extreme concentration of cytotoxic drugs, which cause extensive damage to the endothelial lining of these vessels.
The natural response by the body is to clot the sites of injury. Such a response results in occlusion of these small-diameter vessels and, ultimately, liver failure. Liver failure allows for the kidneys, lungs, and heart, leading to multi-organ failure (MOF) and death. Severe VOD is the most extreme form of VOD and is associated with multiple-organ failure and high rates of morbidity and mortality. The prognosis for patients with severe VOD with MOF is grim, where VOD typically occurs within 30 days of stem cell transplantation, and the survival rate for patients with VOD is 20% or less following 100 days.
Vascular System Disorders
|Endothelial cells that line blood vessels play a crucial role in thrombosis (formation of blood clots), inflammation and cancer.
Symptoms of VOD may begin suddenly, where blockage of the small veins causes the liver to swell with blood, making the abdomen tender to the touch. Fluid may leak from the surface of the swollen liver and accumulate in the abdomen, producing a condition called ascites. Jaundice (a yellowish discoloration of the skin and the whites of the eyes) may also occur.
Risk factor for VOD include: allogeneic SCT, intensity of conditioning regimen, prior hepatic injury, age.
VOD is characterized by hyperbilirubinemia, ascites, hepatomegaly, weight gain >5% over baseline and right upper quadrant pain.
The International Bone Marrow Transplant Registry has estimated that approximately 53,000 people in the US and Europe received blood and bone marrow transplants in 2003. Many of these patients are being treated for hematologic cancers. Based on Gentium’s review of more than 200 published papers, it is estimated that up to 17% of patients who receive blood and bone marrow transplants develop VOD. Approximately one-third of these patients progress to severe VOD and approximately 80% of the patients who develop severe VOD die within 100 days of stem cell transplantation without treatment. Thus, VOD is considered one of the most important and challenging complications of stem cell transplantation.