Bobbie Rhodes-Clark

Quantification, identification, and relevance of anti-human leukocyte antigen antibodies formed in association with the berlin heart ventricular assist device in children.

Background Ventricular assist devices (VADs) are increasingly being used in pediatric patients to provide long-term cardiac support. One potential complication of VAD therapy is the development of antibodies directed against human leukocyte antigens (HLA). This phenomenon has not been well described with the Berlin Heart EXCOR VAD, the most commonly used VAD in pediatric patients. Methods The records of all pediatric patients undergoing VAD support using the Berlin Heart device at our institution between April 2005 and August 2011 were reviewed retrospectively. Demographic and clinical data regarding the VAD course were collected. Assessment of anti-HLA antibodies was performed using Luminex, and antibodies were quantified using mean fluorescence intensity (MFI). Assessment for anti-HLA antibodies was performed before VAD implantation and in serial fashion after VAD implantation. Clinically significant anti-HLA antibodies (sensitization) were defined by an MFI of more than 1000. Results Thirty-six patients were supported with the Berlin Heart VAD; 13 met inclusion criteria. The majority (85%) carried the diagnosis of dilated cardiomyopathy. Evidence of sensitization pre-VAD was found in 69%; new-onset sensitization (the development of new antibodies on VAD) occurred in 69%. All patients survived to transplantation. In two patients, the retrospective crossmatch was positive, but only in one patient was the crossmatch positive for antibodies formed while on VAD. Conclusions Using Luminex and MFI quantification, anti-HLA antibodies are common before VAD implantation in pediatric patients. While on VAD support, new anti-HLA antibodies formed in a majority, but the immediate impact of these antibodies appears to be limited.

Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

Autologous graft versus host disease (autoGVHD) is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs) used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC) products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B) were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P = 0.047). On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells) were found to be significantly lower in patients with autoGVHD (P = 0.038). HLA-B55 expression was significantly associated with development of autoGVHD (P = 0.032). Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

High-Resolution (HR) HLATyping Can Confirm the Diagnosis of Graft Versus Host Disease (GVHD)After Orthotopic Liver-Transplantation (OLT)

Acute graft versus host disease (GVHD) following orthotopic liver transplantation (OLT) is a rare but severe disease. GVHD diagnosis can often be delayed, since the symptoms are non-specific. We present a case of a 62 year-old male with end-stage liver disease who underwent OLT. There were no major peri-transplant complications. Patient presented ~4 weeks post-OLT, with fever,cough, throat discomfort, and rash; and was treated for suspected infection with broad-spectrum antimicrobials. ~5 weeks post-OLT, patient became pancytopenic, and a skin biopsy was suspicious for GVHD. Bone marrow biopsy was performed and revealed extreme pancytopenia with necrosis. The individual pre-OLT patient and donor types were compared at the serologic equivalent and high-resolution (HR) HLA-type, without clear indication of risk for GVHD, and or graft rejection. HR HLA-typing was performed on bone marrow cells obtained post-OLT and compared with the pre-OLT specimen to demonstrate donor lymphoid chimerism. HR typing results from the patient’s bone marrow post-OLT indicated the presence of all four alleles, and along with the clinical features,confirmed the diagnosis of GVHD. This case demonstrates howHR HLA typing can aid in rapid diagnosis and early recognition of GVHD post-OLT.