PREDICTIVE VALUE OF HOST-SPECIFIC DONOR HELPER T-CELL PRECURSOR FREQUENCY FOR ACUTE GRAFT-VERSUS-HOST DISEASE AND RELAPSE IN HLA-IDENTICAL SIBLINGS RECEIVING ALLOGENEIC BONE MARROW TRANSPLANTATION FOR HEMATOLOG

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Abstract
Acute graft-versus-host disease (aGVHD) is still one of the main causes of morbidity and mortality after allogeneic bone marrow transplantation. Attempts to avoid GVHD are associated with an increased risk of relapse, probably because the graft-versus-leukemia effect is also abrogated. It was recently suggested that a high frequency of host-specific donor helper T cell precursors (HTLp) might be predictive of significant aGVHD(grade≥II). We retrospectively studied the frequency of HTLp by means of simplified limiting-dilution analysis to determine its predictive value for aGVHD and relapse. Pre-bone marrow transplantation, host-specific donor HLTp frequencies were analyzed in 32 patients who had received marrow from HLA-identical siblings for hematological malignancies, in terms of aGVHD and relapse. HTLp frequencies were significantly higher in patients who had aGVHD≥ grade II (n=14) than in those without aGVHD (n=18)(P=0.007). Patients who relapsed (n=13) had significantly lower HTLp frequencies than those who did not relapse (n=19)(P<0.0001). The probabilities of relapse(Kaplan-Meïer method) when the HTLp frequency was higher and lower than 1/200,000 were 0% and 88%, respectively(P<0.0001). The definition of HTLp cut-off values predictive of aGVHD and relapse should contribute to donor selection and could open the way to protocols adapting immunomodulation to the likely risk of aGVHD and relapse.

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