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 HEMATOLOGICAL MALIGNANCIES

Background Acute graft-versus-host disease (aGVHD) is still one of the main causes of morbidity and mortality after allogeneic bone marrow t ransplantation, Attempts to avoid GVHD are associated with an increase d risk of relapse, probably because the graft-versus-leukemia effect i s also abrogated, It was recently suggested that a high frequency of h ost-specific donor helper T cell precursors (HTLp) might be predictive of significant aGVHD (grade greater than or equal to II). Methods, 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 HLT p frequencies were analyzed in 32 patients who had received marrow fro m HLA-identical siblings for hematological malignancies, in terms of a GVHD and relapse. Results. HTLp frequencies were significantly higher in patients who had aGVHD greater than or equal to grade II (n=14) tha n in those without aGVHD (n=18) (P=0.007), Patients who relapsed (n=13 ) had significantly lower HTLp frequencies than those who did not rela pse (n=19) (P<0.0001), The probabilities of relapse (Kaplan-Meier meth od) when the HTLp frequency was higher and lower than 1/200,000 were 0 % and 88%, respectively (P<0.0001). Conclusions. The definition of HTL p cut-off values predictive of aGVHD and relapse should contribute to donor selection and could open the way to protocols adapting immunomod ulation to the likely risk of aGVHD and relapse.