HIV+ Boy Dies After HIV-resistant Stem Cell Transplant for Leukemia

A 12-year-old HIV positive boy with acute lymphoblastic leukemia died earlier this month due to graft-versus-host disease complications after undergoing an experimental cord blood transplant in April from a donor with the CCR5-delta-32 (CCR5-Δ-32) mutation, which makes cells resistant to HIV entry, the University of Minnesota announced this week.

Transplantation of cord blood, which contains stem cells, is a recognized treatment for leukemia. In this case, clinicians hoped to replicate the success of the Berlin Patient, Timothy Brown, who remains free of detectable HIV more than 5 years after receiving bone marrow stem cell transplants from a CCR5-Δ-32 donor as a treatment for leukemia. At the time of his death, the boy did not have detectable HIV despite being off antiretroviral therapy.

Transplanted cord blood, which is collected from infant umbilical cords shortly after birth, does not need to be matched as closely as adult bone marrow, but a suboptimal match can still result in the new donor cells attacking the recipient's body. It is unclear in this case whether researchers settled on a less close match in order to find a donor with the uncommon double CCR5-Δ-32 mutation.

Below is an edited except from a University of Minnesota press release describing the case.

Pediatric Patient Dies After Undergoing Historic Transplant at U of M

July 13, 2013 -- On April 23, 2013, University of Minnesota physician-scientists performed the first cord blood transplant in the United States designed specifically to cure a child with HIV/AIDS, as well as a form of acute lymphoblastic leukemia (ALL) that is particularly resistant to chemotherapy alone.

This new treatment was based on the fact that the transplanted cord blood, known to be highly effective in curing leukemia, contained a variant of the cell surface protein CCR5 -- known as CCR5Δ32. Present in less than one percent of the population, CCR5Δ32 prevents most strains of the HIV virus from entering a patient’s T cells, thereby preventing the destruction of the person’s immune system.

The announcement that such a transplant had occurred this past April led to considerable interest from public as well as the HIV community. While the patient’s initial course was remarkably uneventful, in early June he developed a severe complication, called graft-versus-host disease, which occurs when the immune cells of the donor attack various tissues of the body. While he had a partial response to its treatment initially, the patient died on Friday, July 5, 2013.

Until now, the patient’s identity had been kept from the media. Today, with his mother’s permission, we can reveal that the twelve-year-old patient who underwent this pioneering treatment was Eric Blue of Alexandria, Louisiana.

"At the time we took Eric’s case, we knew it was going to be a challenge and that success was never a guarantee," said transplant physician and Masonic Cancer Center researcher Michael Verneris, MD. "Still, we were ready to move this novel treatment approach forward based on the experience of our team with cord blood transplantation generally and availability of HIV experts here at the University. While the entire team is very sad for this family, we also must recognize that we gave him the best chance of beating not one but two life-threatening diseases."

With a team of scientists around the nation, University HIV expert Timothy Schacker, MD, along with Verneris, are evaluating all the tissue and blood specimens that were obtained throughout Eric’s treatment course. While not yet conclusive, the results to date are encouraging, having demonstrated an absence of HIV in all blood specimens even after the discontinuation of the three antiretroviral drugs.

"Certainly much work has yet to be done to prove the absence of any HIV in his tissues," said Schacker. "Over the next month, we will complete the extensive testing and determine just how effective the treatment was at eradicating the HIV and leukemia."

"Eric was an incredibly brave young man," said blood and marrow transplant program director John Wagner, MD, an internationally recognized pioneer in cord blood transplantation at the University of Minnesota. "Even when he was sick, Eric told me that one day he and Timothy Brown would stand together as firsts: Timothy as the first person to be cured of HIV after a bone marrow transplantation and Eric as the first to be cured of HIV after cord blood transplantation from donors with the CCR5 variant."

Wagner added that he hopes Eric’s case compels all cord blood banks worldwide to test the cord blood stem cells for CCR5Δ32 so that physicians can find better matched units for their patients. Not only will this make such treatments more widely available but it will also reduce the risks of such transplant related risks.

Today, very few units within cord blood inventories have been tested for these genetic variants.

7/19/13

Source

J Paquette. Pediatric Patient Dies After Undergoing Historic Transplant at U of M. Press release. July 13, 2013.