The US Food and Drug Administration (FDA) halted 27 gene therapy trials Tuesday following indications that a second child is showing signs of leukemia after treatment for X-linked Severe Combined Immune Deficiency (X-SCID). A group at Great Ormond Street Hospital in the UK will also stop conducting trials as it confers with UK health officials and families of treated children.

Alain Fischer's group at the Necker Children's Hospital in Paris carried out what was largely considered the first unequivocal success in gene therapy. Though at least one researcher has questioned the methods employed by the group, they effectively restored immune function in 10 of 11 patients who would have likely died from X-SCID. Fischer told the FDA last fall and again a month ago that patients were exhibiting leukemia-like symptoms.

The first announcement prompted the FDA to place three SCID trials in the US on clinical hold. Philip Noguchi at the agency's Office of Cellular, Tissue, and Gene Therapies told The Scientist that FDA is now temporarily halting clinical trials that have specific similarities to the X-SCID treatment which may place patients at risk for leukemia. These are therapies that use retroviruses to transfect hematopoietic stem cells and include treatments for AIDS and some cancers.

Cristof von Kalle at Cincinnati Children's Hospital has been working up the blood of both French patients. He told The Scientist that the symptoms and patient characteristics look similar. In the first case von Kalle found that the therapeutic gene had localized with LMO2, an oncogene associated with leukemia. "Perhaps not the same thing, but something similar is going on in the second patient," he said.

Jitendra Mehrishi of the University of Cambridge said that cell separation techniques, and not gene insertion, may be responsible for the complications. Citing evidence that dates back to the 1970s, he told The Scientist that methods and enzymes used to remove platelets from the blood and to precipitate cells may leave artifacts and disrupt the surface integrity of cells to be injected into patients. "Scientists have been alerting, 'Don't use enzymes. Be careful about temperature. Be careful about platelets.' And they go ahead and muck things up."

Both Fischer at Necker and Adrian Thrasher at Great Ormond Street responded by e-mail that they are aware of these concerns, but that similar separation techniques have been used successfully in traditional bone marrow transplant. Von Kalle said that he has not noticed any indications of cell-surface integrity problems.

An FDA Biologics Response Modifiers Advisory Committee meeting on Feb. 28 will further discuss the three halted SCID trials in the US, according to Noguchi. The 27 other trials will move forward as long as they comply with new consent and monitoring standards.