July 16, 2013
In April, doctors at the University of Minnesota announced that they were attempting to reproduce the cure achieved in Timothy Brown in a 12-year old boy with HIV and leukemia who required a stem cell transplant. Due to the challenges associated with identifying appropriate adult stem cell donors homozygous for CCR5Δ32 (as was done for Brown), the Minnesota team -- led by Dr. John Wagner -- obtained cord blood stem cells from the limited available supplies that have been screened for the mutation (the current status of screening efforts is described in a recent review article). Permission was obtained from the Food and Drug Administration (FDA) to conduct the procedure, and it was performed on April 23rd.
On July 12th, the University of Minnesota reported that the boy, Eric Blue, died July 5th from complications associated with transplant. Blue developed severe graft-versus host disease (GVHD), a known risk associated with stem cell transplantation. In the news stories, the doctors express their commitment to honoring Blue's bravery by learning from his case, and highlight the need to expand screening of stored cord blood units for CCR5Δ32 in order to increase the possibility of identifying sources that are suitably HLA-matched for potential HIV-positive recipients.
Cord blood stem transplantation is an evolving field, but current practice is based on matching 6 HLA antigens (fewer than are required for adult stem cell transplants), with a 6:6 match typically viewed as ideal and 4:6 as the minimum acceptable (although some resource websites cite 3:6 as "unlikely, but possible"). There are additional complexities related to the direction of the mismatch and the dose of cord blood that is available. Although the issue does not yet seem to be entirely resolved, it has also been reported that limited mismatches may lead to superior anti-cancer effects under some circumstances. One aspect of Eric Blue's procedure that has not been specifically addressed in the news stories or the University of Minnesota's coverage is the extent to which the CCR5Δ32 homozygous cord blood source was HLA-matched. In order to provide guidance for future attempts to cure HIV-positive people with cancers using CCR5Δ32 homozygous cord blood, it will be important for the doctors and researchers that were involved to report the details of the case.
Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.
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