By Christine Duncan, MD
2009-12-07
While there has been great progress in the prevention and
treatment of transplant-related toxicities,
including graft-versus-host disease (GVHD), transplant-related morbidity and
mortality rates remain unacceptably high. The omnipresent risk of
life-threatening adverse events in the post-transplant setting has
limited the expansion of hematopoietic stem cell transplantation (HSCT) as an
accepted treatment modality for a number of conditions where HSCT might have
value. Today at 10:30 a.m. at the Acute and Chronic GVHD, Infectious
Complications and Immune Reconstitution of Transplantation: Biomarkers of
Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Oral Session
(rooms 243-245), researchers will present their progress in preventing,
identifying, and treating the complications of HSCT.
GVHD remains the most
common complication of allogeneic HSCT; severe GVHD dramatically compromises
quality of life, and can even be lethal. Additionally, the immunosuppression
used to treat GVHD puts patients at risk for life-threatening opportunistic
infections. To effectively prevent and treat GVHD, a comprehensive
understanding of the pathways that lead to the disease is needed. Dr. Mary
Flowers of Fred Hutchinson Cancer
Research Center
will present the results of a study that investigated risk factors for acute
(aGVHD) and chronic GVHD (cGVHD). The group hypothesized that if the risk
factors for aGVHD and cGVHD are discordant, then it is probably because they
result from distinct pathogenic pathways. But the team found that the majority
of aGVHD and cGVHD risk factors are concordant. A team represented by Dr. Marie
Rubio of Necker Hospital
in Paris has
demonstrated another potential risk factor for the development of aGVHD: low numbers of donor-derived invariant
natural killer T cells (iNKT), a recently described population of T cells
involved in immune regulation. The study that Dr. Rubio will describe, of 47
patients who underwent allogeneic HSCT, found that patients with high iNKT
levels had significantly less aGVHD and reduced severity of the illness, which
resulted in greater overall survival.
Dr. Brenda Sandmaier
(also from Fred Hutchinson) will discuss GVHD prevention. She will reveal the results
of a multicenter trial that evaluated the efficacy and safety of three aGVHD
prevention regimens, which consisted of different schedules of tacrolimus and
mycophenolate mofetil, with the possible addition of rapamycin. The regimen
that used all three drugs was associated with the least aGVHD, but the
difference did not achieve statistical significance. Dr. Eva Mischak-Weissinger
of Hannover, Germany, will then present the work
of a multicenter study that investigated the use of a proteomic peptide tool to
identify aGVHD prior to the onset of symptoms. The test had a sensitivity of 76
percent and specificity of 85 percent and is being investigated as a tool to
guide the initiation of therapy.
The session will also
feature presentations by Drs. Thomas Lion of Vienna,
Austria, and Bernd Gruhn of Jena, Germany,
who investigated infection-related toxicities of transplants. Dr. Lion’s group
has developed a PCR test for the identification of more than 80 fungal
pathogens, while Dr. Gruhn’s group has identified a toll-like receptor variant
that appears to be protective against the development of BK virus-associated
hemorrhagic cystitis.
Additional clinical
transplantation sessions today include: Transplantation Regimen Toxicities and
Engraftment: Novel Reduced Intensity Protocols at 7:30 a.m. in rooms 353-355;
Acute and Chronic GVHD, Infectious Complications and Immune Reconstitution of
Transplantation: Immunology of Acute and Chronic GVHD at 2:45 p.m. in rooms
243-245; and Acute and Chronic GVHD, Infectious Complications and Immune
Reconstitution of Transplantation: Infectious Complications and Immune
Reconstitution After Transplantation at 6:00 p.m. in rooms 260-262.
Dr. Duncan indicated no relevant conflicts of
interest.
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