Abstracts (complete list) - Wissenschaft Online

Christine S. Falk, Dominik ter Meer, Iris Bigalke, Alexander Buchner, Barbara
Mosetter, Barbara Simm, Monika Braun, Dusan Prevalsek, Dolores Schendel, Hans-
Jochem Kolb
The Impact of HLA-C and KIR Genetics on Survival of AML
versus ALL Patients following Haploidentical Bone Marrow /
Stem Cell Transplantation.
Introduction: Recent evidence suggests that alloreactive NK cells in haploidentical BMT/
SCT may provide graft-versus-leukemia (GVL) effects. In particular, the constellation of
KIR-positive donor NK cells in absence of inhibitory HLA-C ligands in the patient may
provide advantages for AML patients. Currently, clinical protocols attempt to benefit
from NK alloreactivity by selecting KIR/HLA-C incompatible donors. Materials and
Methods: Since 1996, more than 100 patients with leukemic malignancies have been
transplanted with haploidentical bone marrow at day 0 followed by G-CSF-mobilized T
cell-depleted peripheral blood stem cells (PBSC) at day 6 under immune suppression
(ATG, MTX, CyA). PBSC derived from 37 donors were characterized with respect to NK
and T cell subpopulations prior to and after T cell depletion. Functionality was
determined by cell CD107a degranulation and cytokine secretion against K562 and
some haploidentical recipient cells. HLA-C and KIR genes of 80 patient/donor
combinations were typed by the Luminex-based SSO method. Results and Conclusions:
Although complete haploidentical bone marrow was transplanted at day 0, no
enhancement of acute GVHD compared to HLA-identical matched unrelated BMT was
observed in 98 haploidentical transplanted patients – independently from HLA-C or KIR
constellations. Complete chimerism was established early post transplantation. In
general, T cell-depleted PBSC contained more NK cells than CD34+ stem cells
demonstrating that high numbers of alloreactive NK cells do not correlate with aGVHD.
Functional analyses of NK subpopulations in PBSC prior to and after T cell depletion
revealed i) differences in cytokine secretion among particular donor/recipient
constellations, ii) weak cytotoxic activity against K562, iii) changes in the composition of
KIR-positive and KIR-negative NK subpopulations, vi.) Most importantly, the
combination of HLA-C and KIR haplotypes revealed different constellations for AML vs.
ALL patients that correlate with significantly increased propability of survival.