-
1.
Outcomes of toxoplasmosis after allogeneic hematopoietic stem cell transplantation and the role of antimicrobial prophylaxis
Malek, A. E., Al-Juhaishi, T., Milton, D. R., Ramdial, J. L., Daher, M., Olson, A. L., Srour, S. A., Alatrash, G., Oran, B., Mehta, R. S., et al
Bone marrow transplantation. 2024
-
2.
Development and validation of a risk assessment tool for BKPyV Replication in Allogeneic Stem cell Transplant Recipients
Abudayyeh, A., Lin, H., Abdelrahim, M., Rondon, G., Andersson, B. S., Martinez, C. S., Page, V. D., Tarrand, J. J., Kontoyiannis, D. P., Marin, D., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2020;:e13395
Abstract
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 < 0.0001). 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.
-
3.
HLA-DP mismatch and CMV reactivation increase risk of aGVHD independently in recipients of allogeneic stem cell transplant
Ghobadi, A., Milton, D. R., Gowda, L., Rondon, G., Chemaly, R. F., Hamdi, A., Alousi, A., Afrough, A., Oran, B., Ciurea, S., et al
Current research in translational medicine. 2019
Abstract
HLA-DP mismatched allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with increased risk of aGVHD and decreased risk of relapse with no effects on overall survival (OS). It has been proposed that CMV-reactivation induces expression of HLA-DP molecules on GVHD target tissues by releasing inflammatory cytokines. We hypothesized that the increased GVHD incidence in HLA-DP mismatched allo-SCTs correlates with recipient CMV serostatus or CMV reactivation. In addition, CMV reactivation is associated with increased risk of GVHD with an unknown mechanism. Here, we analyzed the association between HLA-DPB1 and CMV reactivation on cumulative incidence of aGVHD and relapse as well as OS in 613 patients with AML and MDS who underwent matched related or unrelated allo-HCT at MD Anderson Cancer Center from 2005 to 2011. In multivariable analysis, HLA-DPB1 mismatching was associated with increased risk of aGVHD (hazard ratio (HR): 1.53, P < 0.001) independent of CMV serostatus and CMV reactivation. Additionally, HLA-DPB1 mismatching was associated with decreased risk of relapse and no effect on OS. CMV reactivation increased risks of aGVHD (HR: 5.82, P < 0.001) independent of HLA-DP mismatching with no effect on relapse or OS. In conclusion, our data suggests that HLA-DPB1 mismatching and CMV reactivation increase risk of aGVHD independently.
-
4.
Pulmonary impairment following respiratory viral infections is associated with high mortality in allogeneic hematopoietic cell transplant recipients
Sheshadri, A., Chemaly, R. F., Alousi, A. M., Shah, P. K., Rondon, G., Bashoura, L., Kmeid, J., Azzi, J., Blanco, D. W., Kaous, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
INTRODUCTION Pulmonary impairment predicts increased mortality in many settings, and respiratory viral infection (RVI) causes considerable morbidity and mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT). We hypothesized that pulmonary impairment following respiratory viral infection, defined as a decline of forced expiratory volume in 1 second values by ≥10%, may identify allo-HCT recipients at high risk for mortality. METHODS We studied all allo-HCT recipients at our institution who had RVI with respiratory syncytial virus, parainfluenza virus, or influenza from 2004-2013 and had pre-RVI and post-RVI pulmonary function tests. We used competing risk regression models to identify risk factors for 2-year non-relapse mortality (NRM) as the primary outcome after RVI and relapse-related mortality as a competing risk. RESULTS From 223 eligible patients, pulmonary impairment following RVI was associated with over a 3-fold increase in 2-year NRM (pulmonary impairment: 25.3%; no impairment: 7.4%, univariate sub-hazard ratio [SHR] 3.9, 95% confidence interval [CI] 1.9-8.1, p<0.001). After adjusting for age and systemic steroid use, pulmonary impairment following RVI was still associated with increased 2-year NRM (SHR, 3.3 [95% CI, 1.6-6.9]; p=0.002). After adjustment for race and GVHD prophylaxis, chronic GVHD at the time of RVI (OR, 2.8 [95% CI, 1.4-5.4]; p=0.003) and lymphopenia (OR, 2.2 [95% CI, 1.1-4.2]; p=0.02) were associated with increased odds of pulmonary impairment, whereas use of non-myeloablative conditioning was associated with reduced odds of pulmonary impairment (OR, 0.4 [95% CI, 0.2-0.8]; p=0.006). CONCLUSION In allo-HCT recipients with RVIs, pulmonary impairment following RVI is associated with high NRM at 2 years.
-
5.
Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Varma, A., Biritxinaga, L., Saliba, R. M., Stich, M., Jauch, S. F., Afrough, A., Honhar, M., Popat, U. R., Shafi, M. A., Shah, N., et al
Biology of Blood & Marrow Transplantation. 2017;23(4):581-587
Abstract
Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or >=10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n=3) or tenofovir (n=1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P=.4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P=.06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P=.5) and 53 versus 67 months (P=.2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
-
6.
Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients
Abudayyeh, A., Hamdi, A., Abdelrahim, M., Lin, H., Page, V. D., Rondon, G., Andersson, B. S., Afrough, A., Martinez, C. S., Tarrand, J. J., et al
Transplant Infectious Disease. 2017;19(1)
Abstract
BACKGROUND 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. METHODS We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+, CD4+, CD8+, CD56+, NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
-
7.
Prevention of Cytomegalovirus Reactivation in Haploidentical Stem Cell Transplantation
Hammerstrom, A. E., Lombardi, L. R., Pingali, S. R., Rondon, G., Chen, J., Milton, D. R., Chemaly, R. F., Champlin, R. E., Gulbis, A., Ciurea, S. O.
Biology of Blood & Marrow Transplantation. 2017
Abstract
Cytomegalovirus (CMV) infection can increase the morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Because of a higher degree of immunosuppression, haploidentical transplant recipients may be at an increased risk of viral infections, particularly CMV. We retrospectively analyzed 86 haploidentical HCT recipients at our institution to determine whether a more intensified antiviral strategy would reduce the incidence of CMV reactivation compared with a traditional antiviral prophylaxis regimen. According to practice changes over time in antiviral prophylaxis at our institution, patients were divided into the following 3 groups: hybrid (n=15), traditional (n=26), and intermediate dose (n=45). The hybrid group received valganciclovir from admission to day -2 followed by standard-dose valacyclovir. The traditional group received standard-dose valacyclovir starting on day -1. The intermediate-dose group received ganciclovir from admission through day -2, followed by intermediate-dose valacyclovir. The hybrid and intermediate-dose groups were combined into an intensified group for further analysis. We found the cumulative incidence (CI) of CMV reactivation within 100 days post-HCT was higher for patients receiving the traditional strategy compared with the hybrid and intermediate-dose strategy groups (81% versus 53% versus 71%, respectively; P=.08) and was significantly higher when the traditional group was compared against the intensified group (81% versus 67%, respectively; P=.032). Median time to CMV reactivation was also shorter in the traditional group versus the intensified group (31 versus 41 days, respectively). Moreover, the CI of CMV disease by day 100 was significantly worse for patients receiving the traditional prophylaxis strategy among the 3 groups (8% traditional versus 0% hybrid versus 0% intermediate dose; P=.032). Renal toxicity did not differ between the traditional and intensified group. In conclusion, an intensified approach to prevention of CMV reactivation was associated with lower incidence of CMV reactivation and less CMV disease without increased toxicity. Because the most benefit was observed in the intensified group, further studies are needed to assess which antiviral intervention is the most beneficial on lowering the rates of CMV viremia and disease. Copyright © 2017. Published by Elsevier Inc.
-
8.
Outcomes in hepatitis C virus seropositive lymphoma and myeloma patients after autologous stem cell transplantation
Varma, A., Saliba, R. M., Torres, H. A., Afrough, A., Hosing, C., Khouri, I. F., Nieto, Y., Shah, N. D., Parmar, S., Bashir, Q., et al
Bone Marrow Transplantation. 2016;51(7):999-1001
-
9.
Hepatitis C Virus Infection in Patients Undergoing Hematopoietic Cell Transplantation in the Era of Direct-Acting Antiviral Agents
Kyvernitakis, A., Mahale, P., Popat, U. R., Jiang, Y., Hosry, J., Champlin, R. E., Torres, H. A.
Biology of Blood & Marrow Transplantation. 2016;22(4):717-22
Abstract
There is paucity of literature regarding hepatitis C virus (HCV) infection in hematopoietic cell transplant (HCT) recipients. In the study described herein we evaluated several aspects of HCV infection in HCT recipients, including the impact of this infection on cancer status, liver-related outcomes, mortality, and the role of antiviral treatment (AVT), including direct-acting antivirals (DAAs). The medical records of HCV-infected allogeneic and autologous HCT recipients, seen at The University of Texas MD Anderson Cancer Center from August 2009 to November 2015, were reviewed. Patients seen from August 1, 2009 to October 30, 2012 were reviewed retrospectively, whereas those seen from November 1, 2012 to November 30, 2015 were analyzed prospectively in an observational study. Of 434 HCV-infected cancer patients evaluated, 64 underwent 69 HCTs. Most (78%) underwent autologous transplantation. Thirteen percent of patients became HCV-seronegative post-HCT. Compared with patients who did not receive AVT, treated patients had fewer relapses of HCV-associated non-Hodgkin lymphomas (20% versus 86%; P = .015), higher 5-year survival rates (75% versus 39%; P = .02), and a trend toward lower rate of progression to cirrhosis (5% versus 21%; P = .06). AVT discontinuation rate post-HCT was 71% in those receiving IFN-containing regimens and 0% in those receiving DAAs (P < .01). AVT was effective in 12 of 37 patients (32%) and 11 of 13 patients (85%) receiving IFN-based and DAA regimens, respectively (P = .003). HCV is an important cause of morbidity and mortality in this population. HCV seropositivity can be lost post-HCT, posing a diagnostic challenge. Treatment of HCV infection in HCT recipients improves both oncologic and hepatic outcomes. These patients can be successfully treated with DAAs. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.