Development and validation of a risk assessment tool for BKPyV Replication in allogeneic stem cell transplant recipients.

BACKGROUND: BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS: In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS: The total risk score was significantly associated with BKPyV replication (P < .0001). At 30 days after transplantation, the low-risk (score ≤ 0) patients had a 9% chance of developing symptomatic BKPyV replication, while the high-risk (score ≥ 8) of the population had 56% of developing BKPyV replication. We validated the risk score using a separate cohort of 1478 patients. The AUC of the ROC of the risk-score-only model was 0.59. Both the total risk score and 3-level risk variable were significantly associated with BKPyV replication in this cohort (P < .0001). CONCLUSIONS: This grading system for the risk of symptomatic BKPyV replication may help in early monitoring and intervention to prevent BKPyV-associated morbidity, mortality, and kidney function decline.

Early Post-Transplant Minimal Residual Disease Assessment Improves Risk Stratification in Acute Myeloid Leukemia.

We studied if the inclusion of early post-stem cell transplantation (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points, 9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%) at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1 year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either adverse risk category by European Leukemia Net (ELN) or intermediate risk who were aged ≥60 years and/or pre-SCT MRD-positive represented the intermediate-risk group (group 2, 1-year RI 29%). The remaining patients represented the low-risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT, detectable MRD at any time point predicted impending relapse within 2 months. Early post-SCT MRD assessment-combined with pre-SCT MRD assessment, ELN risk category, and age-improves risk stratification for relapse in AML patients post-transplant. Studies aimed at preventing impending relapse in this high-risk population are urgently needed.

Optimal screening for geriatric assessment in older allogeneic hematopoietic cell transplantation candidates.

OBJECTIVE: Older patients who receive hematopoietic cell transplantation (HCT) may be at risk for adverse outcomes due to age-related conditions or frailty. Geriatric assessment (GA) has been used to evaluate HCT candidates but can be time-consuming. We therefore sought to determine the predictive ability of two screening tools, the Vulnerable Elders Survey (VES-13) and the G8, for abnormal GA or frailty. MATERIALS AND METHODS: We enrolled 50 allogeneic HCT candidates age ≥60 years. The GA included measures of medical, physical, functional, and social health. Frailty was defined as 3 or more abnormalities on grip strength, gait speed, weight loss, exhaustion, and activity. We associated baseline characteristics and abnormal GA or frailty. We determined the sensitivity and predictive ability of the VES-13 and G8 for GA and frailty. RESULTS: Overall, 33 (66%) patients (mean age 65.4 years) had an abnormal GA, and 11 patients (22%) were frail. The G8 screening tool had a higher sensitivity for an abnormal GA (69.7%), and the VES-13 had a higher specificity (100%). Both tools had similar discriminatory ability. CONCLUSIONS: Older HCT candidates had a significant number of deficits on baseline GA and a high prevalence of frailty. Existing screening tools may not be able to replace a full GA.

Individual physician practice variation in hematopoietic cell transplantation.

PURPOSE: Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT. METHODS: An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making. RESULTS: Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning. CONCLUSION: These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.

Functional assessment and specific depletion of alloreactive human T cells using flow cytometry.

Human T-cell alloreactivity plays an important role in many disease processes, including the rejection of solid organ grafts and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. To develop a better understanding of the T cells involved in alloreactivity in humans, we developed a cytokine flow cytometry (CFC) assay that enabled us to characterize the phenotypic and functional characteristic of T cells responding to allogeneic stimuli. Using this approach, we determined that most T-cell alloreactivity resided within the CD4(+) T-cell subset, as assessed by activation marker expression and the production of effector cytokines (eg, tumor necrosis factor alpha [TNF]alpha) implicated in human GVHD. Following prolonged stimulation in vitro using either allogeneic stimulator cells or viral antigens, we found that coexpression of activation markers within the CD4(+) T-cell subset occurred exclusively within a subpopulation of T cells that significantly increased their surface expression of CD4. We then developed a simple sorting strategy that exploited these phenotypic characteristics to specifically deplete alloreactive T cells while retaining broad specificity for other stimuli, including viral antigens and third-party alloantigens. This approach also was applied to specifically enrich or deplete human virus-specific T cells.

Blood and marrow transplantation compensation: perspective in payer and provider relations.

The high cost per patient of hematopoietic cell transplantation (HCT) causes this therapy to be the focus of much controversy, given the competing societal demands to provide all possible therapy to preserve life while simultaneously limiting global health care expenditures. Treatment and eligibility decisions for HCT often are heavily scrutinized by both governmental and private payers and not simply determined by physicians, facility providers, and the patient. In an effort to control costs, payers have administrative infrastructure to review resource utilization by these patients. Additionally payers have developed payment methodologies, usually in the form of a case rate payment structure, that place facilities and physician providers of HCT at financial risk for adverse patient financial outcomes in an effort to promote optimal utilization and selection of patients for HCT. As providers enter into such financial risk arrangements with payers, the providers need to understand the true cost of care and be able to identify predictable and unpredictable outlier risks for the financial consequences of medical complications. HCT providers try to protect themselves from excessive financial risk by having different payment rates for different types of transplant, eg, autologous versus HLA or genotypically matched related versus HLA mismatched transplants. Because at certain times in the HCT process risk is more unpredictable, HCT providers require different payment system strategies for the different time periods of care such as evaluation, pre-transplant disease management, harvesting, and cell processing, as well as short- and long-term follow-up. Involvement by clinicians is essential for this process to be done well, especially given the rapid changes technological innovation brings to HCT. Constant dialogue and interaction between providers and payers on these difficult financial issues with HCT is essential to preserve patient access to this potentially lifesaving therapy.