Medical Professional Publications

Anicteric Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation in Children

(From the November 2015 Issue of PediatricsOnline)

Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a relatively common and sometimes fatal complication of hematopoietic stem cell transplant in children. Early diagnosis and treatment of VOD are critical for the patients who develop it. But researchers from Nationwide Children’s Hospital have found that more than 30 percent of the hospital’s patients diagnosed with VOD would not have been diagnosed with the disease under one commonly used criteria.

The so-called “Baltimore criteria,” first published in 1987, require a patient to have hyperbilirubinemia of greater than 2 mg/dL and meet two of these other three measures: weight gain of greater than 5 percent, hepatomegaly or ascites. Patients with anicteric VOD, however, have serum bilirubin levels equal to or less than 2 mg/dL, so would not meet the definition of VOD under the Baltimore criteria.

“Some studies suggest that bilirubin levels are directly correlated with the severity of VOD, and so those levels are important,” says Rajinder P. Bajwa, MD, a member of the Section of Hematology, Oncology and Blood and Marrow Transplantation and senior author of the study. “Patients with anicteric VOD should not be overlooked as they can also have significant morbidity and mortality.”

To better diagnose VOD, Bajwa and his collaborators recommend using the “Seattle criteria,” first published in 1984. This requires patients to meet two of these measures: weight gain of greater than 2 percent or ascites, hepatomegaly or hyperbilirubinemia of greater than 2 mg/dL. The Seattle criteria do not mandate hyperbilirubinemia for a VOD diagnosis.

The study, published in the journal Bone Marrow Transplantation, reviewed the medical charts of patients diagnosed with VOD while undergoing hematopoietic stem cell transplant from 1992 through June 2014 at Nationwide Children’s. A total of 29 patients were included in the final analysis and both Baltimore and Seattle criteria were retroactively applied to them.  Nine were identified with anicteric VOD and 20 with icteric VOD. Two patients with anicteric VOD and 12 with icteric VOD died from complications of the disease.

In seven of the anicteric cases, curative treatment with defibrotide was delayed from one to 11 days because of lack of hyperbilirubinemia. So the study found that even when hyperbilirubinemia was not considered a mandatory criterion for VOD, therapy did not begin soon after diagnosis.

Dr. Bajwa and his colleagues recommend using the Seattle criteria for patients at risk of developing VOD, and beginning treatment as soon as criteria are met and other causes have been ruled out.

“Do not wait for bilirubin levels to go up,” Dr. Bajwa says. “Early diagnosis and initiation of treatment has been shown to lead to better outcomes for patients with VOD.”

Dr. Bajwa and his collaborators are continuing research into the diagnosis and treatment of VOD to devise consensus guidelines for management of the disease. A study nearing completion uses a survey to examine different approaches to VOD among physicians.

“We are learning that there is a lot of variation in the management of VOD in institutions across North America,” Dr. Bajwa says. “Some use the Baltimore criteria while others use the Seattle criteria, and  these variations in diagnosis and treatment should be removed.”

Naples JC, Skeens MA, Auletta J, Rangarajan H, Abu-Arja R, Horwitz E, Stanek J, Bajwa RS. Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children. Bone Marrow Transplantation.  2015 Sep 14 [Epub ahead of print].   

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