Endothelial and Complement Activation As Predictors of Survival in Adult Allogeneic Hematopoietic Cell Transplantation
[Impact of poor graft function on cytomegalovirus pneumonia in patients who have undergone haploidentical stem cell transplantation]
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2020;41(7):552-556
Objective: To retrospectively analyze the impact of primary PGF on CMV pneumonia in patients who have undergone haplo-HSCT. Methods: The clinical data of 122 patients who underwent haplo-HSCT at the Peking University Institute of Hematology from 2011-2012 were retrospectively reviewed. The incidence rate of CMV pneumonia between PGF and good graft function (GGF) was compared, and the factors were analyzed. In addition, outcomes in PGF patients with CMV pneumonia have been described. Results: Total 122 patients were retrospectively reviewed, and of these, 26 (21.3% ) had PGF, while 96 (78.7% ) had GGF. In addition, 15 patients had CMV pneumonia, and the median time to the development of CMV pneumonia was 103 (31-262) days; the 1-year cumulative incidence of CMV pneumonia was 12.3% (95% CI 6.2% -18.4% ) . In patients with primary PGF and GGF after Haplo-HSCT, the incidence of CMV pneumonia was 30.8% (8/26) and 7.3% (7/96) , respectively (P=0.002) . Moreover, 24 patients had CMV viremia (92.3% ) , while of the 96 GGF patients, 79 (82.3% ) had CMV viremia (P=0.212) . In multivariate analysis, the results showed that primary PGF had a significant influence on CMV pneumonia (P=0.005) . Compared with those without CMV pneumonia, patients with CMV pneumonia had poorer overall survival 37.3% (95% CI 11.2% -63.4% ) vs. 78.9% (95% CI 72.0% -87.6% ) (?(2)=16.361, P<0.001) . The 1-year overall survival (OS) was 25.0% (95% CI 0% -55.0% ) and 50.0% (95% CI 26.9% -73.1% ) (?(2)=4.656, P=0.031) in PGF patients with (8/26) and without (18/26) CMV pneumonia. Conclusion: The incidence of cytomegalovirus pneumonia in patients with primary poor graft function increases and the survival rate decreases.
Vancomycin use and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation
Blood advances. 2020;4(12):2640-2643
Predicting non-relapse mortality following allogeneic hematopoietic cell transplantation during first remission of acute myeloid leukemia
Bone marrow transplantation. 2020
The aim of this study was to develop a comprehensive system for predicting non-relapse mortality after allogeneic hematopoietic cell transplantation (HCT) during first complete remission (CR) of acute myeloid leukemia (AML). After dividing 2344 eligible patients randomly into a training set and a validation set, we first identified and scored five parameters, that is, age, sex, performance status, HCT-comorbidity index (HCT-CI), and donor type, on the basis of their impact on non-relapse mortality for patients in the training set. The non-relapse mortality-J (NRM-J) index using the sum of these scores was then applied to patients in the validation set, resulting in a clear differentiation of non-relapse mortality, with expected 2-year rates of 11%, 16%, 27%, and 33%, respectively (P?0.001). The estimated c-statistic was 0.67, which was significantly higher than that of the European Society for Blood and Marrow Transplantation score (0.60, P?=?0.002) and the HCT-CI (0.57, P?0.001). The NRM-J index showed a significant association with overall survival, but not with relapse. Our findings demonstrate that the NRM-J index is useful for predicting post-transplant non-relapse mortality for patients with AML in first CR, for whom the decision of whether to perform allogeneic HCT is critical.
Phenotypes and Baseline Risk Factors of Acute Kidney Injury in Children After Allogeneic Hematopoietic Stem Cell Transplantation
Frontiers in pediatrics. 2020;8:499
Background: Acute kidney injury (AKI) is a frequent and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite relatively high prevalence, AKI after allo-HSCT and its risk factors in children remain obscure. The aim of this study was to describe the prevalence and course of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with baseline characteristics. Methods: Retrospective single-center chart review of all patients under 18 who underwent allo-HSCT during 2011-2017 was performed. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Recurrent AKI and acute kidney disease (AKD) were defined according to the Acute Disease Quality Initiative consensus. Demographic, clinical, and procedure-related characteristics were recorded at the day of HSCT. Results: Fifty-one patients (68.6% boys) with a median age of 9 years (range: 0.25-17) were included. During a median follow-up of 82 (IQR, 60-98) days, 27 (52.9%) patients experienced a total of 39 AKI episodes, translating into one AKI episode per 100 patient days. Multiple AKIs occurred in 11 (21.6%) patients and 18 (35.3%) progressed to AKD. Four patients died, all with ongoing or previous AKI. Patients with AKD were, on average, older (10 vs. 6 years; p = 0.03) and had higher baseline body mass index (BMI) [standard deviation score (SDS) 0.83 vs. 0.04, p = 0.05], whereas patients with recurrent AKI had higher baseline estimated glomerular filtration rate (eGFR) (244.1 vs. 193.9 ml/min/1.73 m(2), p = 0.02). In the adjusted Cox models (HR; 95% CI), older age (1.10; 1.01-1.20) was associated with higher risk of overall AKI and higher eGFR (1.02; 1.01-1.04) was associated with higher risk of recurrent AKI, while older age (1.17; 1.04-1.31), higher eGFR (HR 1.01; 1.0-1.02), and higher BMI SDS (1.66; 1.01-2.72) were associated with higher risk of AKD. Conclusions: AKI is a frequent early complication of allo-HSCT in children, and approximately one fifth experience AKI recurrence and one third develop AKD. Older age, higher BMI, and higher eGFR at the day of transplant may have an effect on the risk of AKI development and its course.
Pediatric hematopoietic cell transplantation: Longitudinal trends in body mass index and outcomes
Pediatric transplantation. 2020;:e13844
Pediatric recipients of HCT may have a high susceptibility for overweight and obesity, and obesity may negatively impact post-transplant mortality and survival. This is a single-center retrospective analysis of 297 pediatric patients who received HCT between 2005 and 2018. Patients were classified as UW, NW, OW, or OB based on age-adjusted BMI. A mixed-effects linear regression model controlling for patient, disease, and transplant-related characteristics was used to trend weight longitudinally. Comparisons were made between weight category and post-transplant outcomes. In the pretransplant period, 5.4%, 54.5%, 22.2%, and 17.8% of patients were UW, NW, OW, and OB, respectively. Five years post-transplantation, those numbers were 10.6%, 48.2%, 16.5%, and 24.7%. Overall, BMI increased 0.00094 ± 0.0001 kg/m(2) each day post-transplant (P < .001), with older individuals demonstrating greater rates of increase. Further, there was a larger BMI increase in patients without TBI compared with those who received TBI (1.29 ± 0.49, P = .008). Rates of acute GVHD, chronic GVHD, and viral infections, in addition to time to platelet and neutrophil engraftment and 5-year survival estimates, were not significantly different based on pretransplant BMI. Overweight and obese individuals had poorer 5-year survival based on 100-day post-transplant BMI (P = .02). Overall, pediatric HCT recipients are at risk of developing obesity, which is associated with decreased survival. Adolescents and young adults demonstrate the highest risk of weight gain, representing a vulnerable population that requires close monitoring, additional interventions, and further research.
The role of candidate genetic polymorphisms in the interaction between voriconazole and cyclosporine in patients undergoing allogeneic hematopoietic cell transplantation: An explorative study
Current research in translational medicine. 2020
PURPOSE To evaluate polymorphisms in genes of drug metabolizing enzymes and transporters involved in cyclosporine and/or voriconazole disposition among patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). METHODS DNA from forty patients was genotyped using the DMETPlus array. The average ratio of cyclosporine concentration/dose (C/D in (ng/mL)/(mg/kg)) per participant's weight was computed using available trough levels and daily doses. RESULTS The C/D cyclosporine ratio was significantly higher when it was administered with voriconazole as compared to when it was administered alone: median: 116.75 vs. 25.40 (ng/mL)/(mg/kg) with and without voriconazole respectively, (P < 0.001). There was also a significant association between the C/D cyclosporine ratio combined with voriconazole and the ABCB1 2677 G > T > A (rs2032582) genetic polymorphism (P = 0.05). In parallel, ABCB1 variant allele carriers had higher creatinine in combination therapy with a median creatinine (mg/dL) of 0.74 vs. 0.56 for variant allele carriers vs. reference; P = 0.003. Interestingly, CYP2C9, CYP2C19, and CYP3A5 extensive metabolizers tended to be associated with lower cyclosporine C/D ratio when combined with voriconazole, but the results were not statistically significant. CONCLUSION To the best of our knowledge, this is the first pharmacogenetic study on the interaction between voriconazole and cyclosporine in patients undergoing allo-HCT. Results suggest that the ABCB1 2677 G > T > A genetic polymorphism plays a role in this interaction with cyclosporine related nephrotoxicity. Pre-emptive genotyping for this genetic variant may be warranted for cyclosporine dose optimization. Larger studies are needed to potentially show significant associations with more candidate genes such as CYP3A4/5, CYP2C9, and CYP2C19, among others.
Impact of donor and recipient characteristics on graft-versus-host disease and survival in HLA-matched sibling hematopoietic stem cell transplantation
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;:102743
OBJECTIVE To analyze the impact of donor- and recipient-related factors on Graft-versus-host disease (GVHD) and overall survival of transplantation from matched sibling donors. METHOD we retrospectively analyzed the clinical features of 68 consecutive hematological patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling from 2011 and 2017. RESULTS The incidence of - acute GVHD (aGVHD) and chronic GVHD (cGVHD) after transplantation was 13.6 % and 19.7 %, respectively. We also noted the donor and recipient characteristics had no impact on - aGVHD incidence.We found sex mismatch (F-M) did not increase the risk of cGVHD in the model if a female donor was younger than 30 years (P = 1.000), but cGVHD increased if the female donor was ≥30 years (P = 0.002). Recipients≥40 years undergoing HCT from donors ≥30 years were at higher risk for cGVHD (P = 0.021). Development of - aGVHD and cGVHD had no effect on overall survival (P = 0.159, 0.081). Non-remission status at allo-HCT was linked to lower overall survival (P = 0.001). CONCLUSION The incidence of cGVHD was higher when male recipients received hematopoietic progenitor cells from female ≥30 years donors, and when older than 40 years recipients received hematopoietic progenitor cells from ≥30 years donors. Patients in non-remission status at allo-HCT was inclined to have lower overall survival.
Relapse of acute myeloid leukemia after allogeneic hematopoietic cell transplantation: clinical features and outcomes
Bone marrow transplantation. 2020
Posttransplant relapse represents the greatest obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) for patients with acute myeloid leukemia (AML). This study investigated clinical features and outcomes of posttransplant relapse of AML based on data for 1265 patients with AML suffering relapse after allogeneic HCT conducted during complete remission (CR). Relapse occurred at a median of 6.1 months. The incidence rate of relapse peaked at 29.0 per 100 patient-years during the first 3-6 months period post transplant, after which the rate declined over time, and after 3 years remained consistently at less than 1 per 100 patient-years. The probability of overall survival (OS) after posttransplant relapse was 19% at 2 years, with 68% of deaths being attributed to leukemia. The interval from transplantation to relapse was identified as the strongest indicator for OS. Donor lymphocyte infusion (DLI) and second allogeneic HCT (HCT2) were administered to 152 (12%) and 481 (38%) patients, respectively. Landmark analyses showed some signs of survival benefit when these procedures were performed during CR, but no benefit was gained when performed during non-CR. Our findings clarify clinical features of posttransplant relapse of AML, and indicate the urgent need for developing effective bridging to cellular therapies.
The value of (18)F-FDG PET/CT in the prediction of clinical outcomes of patients with acute leukemia treated with allogeneic hematopoietic stem cell transplantation
Oncology letters. 2020;20(5):175
The present study aimed to determine whether (18)F-FDG PET/CT performed before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) can predict clinical outcomes in acute leukemia (AL). A total of 79 examinations comprising 72 patients with AL who underwent (18)F-FDG PET/CT before and/or after allo-HSCT were retrospectively enrolled between January 2011 and January 2019. Outcomes were assessed using overall survival (OS) and disease-free survival (DFS). A total of 63 examinations were PET-positive, while 16 examinations were PET-negative. Increased BM and splenic (18)F-FDG uptake were observed in 24 (19/79) and 14% (11/79) of examinations, respectively. (18)F-FDG-avid lymph nodes were observed in 38% (30/79) of examinations. E(N)E(M)E(S) involvement was detected in 44% (35/79) of examinations. The presence of E(N)E(M)E(S) involvement [OS hazard ratio (HR), 6.399; 95% confidence interval (CI), 1.843-22.224; P=0.003; post-HSCT OS HR, 7.203; 95% CI, 1.510-34.369; P=0.013; DFS HR, 3.671; 95% CI, 1.145-11.768; P=0.029], post-transplantation minimal residual disease (DFS HR, 4.381; 95% CI, 1.594-12.040; P=0.004; pre-HSCT OS HR, 11.455; 95% CI, 1.336-98.179; P=0.026) and disease status (OS HR, 0.330; 95% CI, 0.128-0.848; P=0.021; post-HSCT OS HR, 0.195; 95% CI, 0.050-0.762; P=0.019; DFS: HR, 0.278; 95% CI, 0.091-0.851; P=0.025) could serve as an adverse prognostic factor in patients with AL treated with allo-HSCT. (18)F-FDG PET/CT before and/or after allo-HSCT was a predictor for OS and DFS in patients with AL. E(N)E(M)E(S) involvement detected using (18)F-FDG PET/CT may help identify patients with AL who are likely to have unfavorable clinical outcomes.