ALLORESPONSES IN TOLERANT RECIPIENTS OF COMBINED KIDNEY/BONE MARROW TRANSPLANTATION WITH NON-MYELOABLATIVE CONDITIONING

Abstract

P931 Introduction: We analyzed in vitro responses in 6 patients who received combined non-myeloablative HLA-matched sibling bone marrow (BM) and kidney transplantation (Tx) for the treatment of multiple myeloma (MM) with renal failure. Patients 3 - 6 were participants in an Immune Tolerance Network study. Methods: Mixed lymphocyte reaction (MLR), cell-mediated lymphocytotoxicity (CML), and limiting dilution assays (LDA) were performed. Donor chimerism was monitored by microsatellite analysis. T cell recovery was followed by flow cytometry. Results: In Patient 1, initial multilineage mixed chimerism declined to undetectable levels after Day 105. CyA was discontinued on Day 73 and the transplanted kidney has shown no evidence of rejection > 5.5 years. Early CD8 T cell recovery and strong anti-donor cytotoxic T lymphocyte (CTL) responses were seen in CML and LDA, without anti-donor MLR responses. The myeloma is in complete remission (CR) > 5.5 years. In Patient 2, initial mixed chimerism became undetectable after Day 123. CyA was discontinued on Day 77 and the kidney has shown no rejection > 3 years. Early recovery of anti-3rd party responses but not anti-donor responses were seen in MLR and CTL and helper T lymphocyte (HTL) LDA. Urinary light chain was reduced by 90% after Tx, but the myeloma later progressed. In Patient 3, multilineage mixed chimerism converted to donor full chimerism by Day 62. MMF was added to control mild chronic GvHD and CyA was discontinued on Day 379. The patient showed transient anti-donor responses in MLR and CTL-LDA prior to conversion to donor full chimerism, and high anti-host CTLp frequencies following conversion to donor full chimerism. The kidney has shown no rejection. The patient is in CR > 30 months. In Patient 4, initial mixed chimerism declined to undetectable levels by Day 71. CyA was discontinued on Day 60. The kidney has shown no rejection > 21 months. Early recovery of anti-3rd party responses but not anti-donor responses were seen in MLR and CTL and HTL-LDA. Urinary light chain persisted post-Tx. In Patient 5, multilineage mixed chimerism converted to donor full chimerism by Day 90. CyA was discontinued on Day 35. The patient showed transient anti-donor responses in HTL and CTL-LDA prior to conversion to donor full chimerism, and high anti-host CTLp frequencies following conversion to donor full chimerism. The kidney has shown no rejection. In Patient 6, initial mixed chimerism was observed, but became undetectable by Day 98. CyA was discontinued on Day 60. The kidney has shown no rejection > 3 months. No anti-donor responses were seen in MLR and CTL and HTL-LDA, but a high anti-host HTLp frequency was seen on POD70. Conclusions: Combined kidney/BMTx with non-myeloablative conditioning for MM patients is a promising strategy for successful induction of renal allograft tolerance and also provides potent anti-myeloma effects. Donor marrow rejection and anti-donor alloresponses can appear in patients despite maintenance of tolerance to donor kidneys.