Charles Martinez

General and Virus-Specific Immune Cell Reconstitution after Double Cord Blood Transplantation.

Cord blood transplantation (CBT) is curative for many patients with hematologic malignancies but is associated with delayed immune recovery and an increased risk of viral infections compared with HLA-matched bone marrow or peripheral blood progenitor cell transplantation. In this study we evaluated the significance of lymphocyte recovery in 125 consecutive patients with hematologic malignancies who underwent double-unit CBT (DUCBT) with an antithymocyte globulin-containing regimen at our institution. A subset of 65 patients was prospectively evaluated for recovery of T, natural killer (NK), and B cells, and in 46 patients we also examined viral-specific T cell recovery against adenovirus, Epstein-Barr virus, cytomegalovirus, BK virus, respiratory syncytial virus, and influenza antigen. Our results indicate that in recipients of DUCBT, the day 30 absolute lymphocyte count is highly predictive of nonrelapse mortality and overall survival. Immune recovery post-DUCBT was characterized by prolonged CD8+ and CD4+ T lymphopenia associated with preferential expansion of B and NK cells. We also observed profound delays in quantitative and functional recovery of viral-specific CD4+ and CD8+ T cell responses for the first year post-CBT. Taken together, our data support efforts aimed at optimizing viral-specific T cell recovery to improve outcomes post-CBT.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause‐specific hazard of kidney function decline, and the Fine–Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft‐versus‐host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.

Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients

BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant‐associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery.

Overview of Electronic Data Sharing: Why, How, and Impact

Electronic data sharing is a critical, but underappreciated, requirement for modern medical informatics systems. This capability is facilitated by acquisition of structured clinical data, but optimized only if this data is stored and transmitted using standardized representations. Most electronic medical record and clinical trials management systems are poorly suited for data sharing. In the near future, sharing clinical outcome data is likely to become very important, so these capabilities must be improved. In this article, basic concepts of electronic data sharing are reviewed and their use illustrated in a data-sharing project developed to support Hematopoietic Cell Transplantation reporting to a national database.

Stem Cell Transplantation and Informatics: Current Considerations

Informatics strategies and applications available to stem cell transplant (SCT) programs are diverse and changing rapidly. Although most hospitals have electronic medical records (EMRs), few are equipped with specialized SCT applications. Most EMRs do not contain critical elements to support SCT practice and research. Strategies to optimize information technology resources to support SCT programs are reviewed and technical and workflow support discussed. Guidance and rationale for the use of both SCT applications and EMRs are emphasized.

Comprehensive stem cell transplant (SCT) outcome data submission.

293 Background: All U.S. transplant centers must report comprehensive SCT outcome data to a federal registry. The current electronic data capture method requires manual data entry of 700+ unique data elements into an internet application, FormsNet (Center for International Blood and Marrow Transplant Research). Data is routinely copied from program databases or the EMR by manual transcription, an inefficient, inaccurate and expensive process. A method was needed to allow electronic transmission of outcome data directly from these databases to the mandated SCT Outcomes Database (SCTOD). METHODS We designed an interface engine (IE) to transmit structured data through a caGRID subnet (AGNIS) directly to the SCTOD from a proprietary MDACC SCT database using a secure, auditable method. To make this method applicable to other centers, we collaborated with the NCI and others to expand the Biomedical Research Informatics Domain Group (BRIDG) standard data model to support a full set of granular data elements (>1,900) required to describe SCT outcomes. The IE was modified to transmit SCT data from the expanded BRIDG database to the SCTOD. The IE and expanded BRIDG database model will be made available to all centers without charge. In this way centers interfacing data to this new structure can transmit data to the SCTOD without transcription. RESULTS The BRIDG oversight committee has approved the extended model and made its structure and content publically available. The IE has been used to transmit >4,000 data forms from MDACC to the SCTOD. The full set of SCT common data elements (CDE) has been published in the Cancer Data Standards Repository of the NCI. The American Society of Blood and Marrow Transplantation is publishing an RFA to identify 1-3 vendors qualified to interface data from center-specific systems to the BRIDG database. CONCLUSIONS Comprehensive and direct electronic data transmission to the SCTOD is feasible and can be done without modifying individual centers legacy applications. The plan will make appropriate tools available to all transplant centers. This paradigm should be applicable to other areas of oncology.