Marek Ussowicz, Poland
Wrocław Medical University Dept of Pediatric Hematology and Oncology, BMT Unit CIC 817Presenter of 2 Presentations
SALVAGE ALPHA-BETA T-CELL DEPLETED HAPLOIDENTICAL STEM CELL TRANSPLANTATION IN AN IPEX SYNDROME PATIENT – CASE REPORT
Abstract
Background and Aims
The IPEX syndrome is the X-linked immunodysregulation syndrome, with poliendocrynopathy, and enteropathy caused by the FOXP3 mutation. Clinical hallmarks are enteropathy, endocrinopathy and dermatitis.
Methods
We report the patient with classical IPEX syndrome who developed insulin-dependent diabetes, autoimmune thyroiditis, nephrotic syndrome and coeliac disease. The patient was transplanted with an unrelated 8/10 HLA matched umbilical cord blood (UCBT) after conditioning regimen with treosulfan 36 g/m2, fludarabine 150 mg/m2, thiotepa 10 mg/kg, and Thymoglobulin at a dose of 7.5 mg/kg. Due to rapid and complete rejection of the UCBT, a second transplantation from a 6/10 HLA matched mother was performed.
Results
The second conditioning regimen consisted of busulfan 16 mg/kg, fludarabine 150 mg/m2, cyclophosphamide 1g/m2, Grafalon at a cumulative dose of 30mg/kg, and rituximab at a dose of 375 mg/m2. The donor underwent stem cell apheresis on day -1, and alpha-beta T-cell depletion was performed using the CliniMacs Prodigy. The graft product contained 15.06 x 106 CD34+ cells/kg BW and 4.19 x 105 alpha-beta T-lymphocytes/kg BW. From day +15 to +18, due to acute graft rejection the boy was treated with Thymoglobulin and the full donor chimerism was achieved. Around day +40 after transplantation, the boy developed symptoms of stage 1 skin graft versus host disease and was treated with topical steroids and mycophenolate mofetil. Three years after SCT, the patient remains free from GVHD and immunosuppression.
Conclusions
Haploidentical SCT in IPEX syndrome is feasible and well tolerated, but chimerism monitoring and aggressive graft rejection therapy are warranted due to hyperreactivity of autologous T-lymphocytes.
THE PRESENCE OF KIR-LIGAND GRAFT-VERSUS-HOST MISMATCH AFFECTS OS, AND EFS IN CHILDREN AFTER ALLOGENEIC STEM CELL TRANSPLANTATION.
Abstract
Background and Aims
Killer immunoglobulin-like receptors (KIR) play a role in regulation of NK-lymphocyte reactivity and affect immunological response in stem cell transplantation (SCT) recipients.
Methods
Patients were transplanted for malignant (89) or non-malignant diseases (113) from matched sibling donors (MSD, 35), matched donors (MD, 133) or partially matched donors (MMD/HAPLO, 33). The donor samples were tested for KIR genotype using KIR typing kit (Miltenyi, DE). The effects of diagnosis, degree of HLA-match, pre-transplant conditioning, and KIR-genotyping results on survival were analyzed.
Results
Neither differences in single KIR loci, nor the KIR B-content score affected patients’ OS/EFS/TRM/DFS. The graft-versus-host (GVH) KIR-ligand mismatch was observed in 13 patients and host-versus-graft (HVG) in 9 cases. The probability of OS was superior in non-malignant entities 83.96 % vs 60.5% (p=0.0004). Better donor choice (MSD vs MUD vs MMD/HAPLO) was associated with higher probability of OS (94.3% vs 80% vs 31.2%, p=0.00001) and EFS (88.6% vs 77% vs 28.8%, p=0.00001). The probability of OS was decreased in the presence of any HLA mismatch (61.02% vs 88.99%, p=0.00008), and GVH KIR mismatch (41.6% vs 81.5%, p=0.002). The multivariate analysis using the Cox regression model revealed GVH KIR mismatch as the factor relevant for OS, EFS, HVG mismatch for TRM, and in non-malignant entities degree of donor’s HLA B match was significant for OS.
Conclusions
KIR associated mechanisms affect patients outcome after SCT. In case of partially matched donors, the optimal donor choice algorithm should eliminate the presence of KIR ligand GVH mismatch.