Pretransplantation minimal residual disease monitoring by multiparameter flow cytometry predicts outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation

Background and purposeIs minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) prognostic for acute myeloid leukemia (AML) patients before allogeneic hemopoietic stem cell transplantation (allo-HSCT)? And if so, what level of MRD eradication can be used to help guide the timing of HSCT? Can haplo-HSCT improve the prognosis of AML patients with MRD positive? To figure out these questions, we initiated this retrospective study.Methods96 AML patients were included retrospectively and divided into 5 groups, according to pre-transplantation MRD levels (from 5 × 10⁻² to <1 × 10⁻⁴), to analyze the overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR). Secondly, we compared the prognosis of MRD-negative (MRD^neg) and MRD-positive (MRD^pos) AML patients (cutoff value = 1 × 10⁻³) who underwent allo-HSCT, and further analyzed the prognosis of MRD^pos patients after received different transplantation modalities.ResultsIt is found that the 2-year OS and DFS of MRD negative group were better than the MRD positive group, and that the deeper the eradication of MRD before transplantation, the better the prognosis of patients. The CIR in patients received HLA-identical transplantation, was higher in the MRD^pos than in the MRD^neg. Haploid transplantation reduced the CIR disparity between MRD^pos and MRD^neg group. Subsequently, in AML patients who remain MRD positive before HSCT, we show that haplo-HSCT offered a better prognosis than HLA-identical transplantation (MSDT and MUDT).ConclusionIt is suggested that achieving MFC-MRD <10⁻³ (10⁻⁴ or even better) before allo-HSCT could reduce the relapse of AML and improve OS and DFS significantly, while haplo-HSCT may be preferred for patients not achieving MRD negativity.     

Psycho-social health and quality of life among kidney donors following transplantation

IntroductionLiving kidney donation is a complex psychological experience for donors. The present study examined the psychosocial impact of kidney donation on donors.MethodsThe retrospective study included 506 donors who donated a kidney between 2010 and 2018 at a transplant centre in India. These donors responded via a donor insight questionnaire about their hospital anxiety, and their possible level of depression. The information included socio-demographic form with multiple information. The health survey was used periodically evaluate the psychosocial impact among donors following donation, including the transplant outcomes.ResultsThe majority of donors were females (79.4%). There was a significant improvement in the quality of life among donors (SF-36) following the donation of a kidney, especially among those donors who maintained good graft functions themselves as well as those who were informed about good kidney function in transplanted recipients. These donors showed a lesser degree of depressive and anxiety scores (HAD score 3.5 and BDI II 4.8) than donors who had problems themselves and/or whose donated kidneys did not function well. Most living donors (89.1%) felt that the act of donation had a positive impact on their lives and those donors would encourage others to donate a kidney. Overall, the graft outcomes impacted the donor's state of mind.ConclusionThe study showed a very positive impact of the acknowledgment of the donor by the recipient, especially those donors whose kidney transplants were well functioning. The state of depression, anxiety, and psycho-social outcomes correlated with the graft outcomes. Donors showed positive insight towards donation, with inner conscience still conclusively willing to donate and encourage others.     

Effects of HIF-1α, hepcidin and PTH on RankL in patients with chronic kidney disease in different stages

ObjectiveTo investigate the effects of hypoxia-inducible factor-1α (HIF-1α), hepcidin, and parathyroid hormone (PTH) on the serum nuclear factor κB and receptor activating factor ligand (RankL) in patients with chronic kidney disease (CKD) stages 3–5.MethodsA total of 90 patients admitted to our hospital's Department of Nephrology from March 2018 to December 2019 were randomly selected as the subjects (30 patients with CKD3, CKD4, and CKD5 each). A total of 30 healthy volunteers receiving a physical examination in our hospital during the same period were selected for the control group. Then, the participants' HIF-1α, hepcidin, and RankL levels were detected by double-antibody sandwiched enzyme-linked immunosorbent assay. The serum creatinine, serum iron, hemoglobin, and phosphorus (P³⁺) levels were determined by BeckMAN-c800 automatic biochemical analysis. The glomerular filtration rate (eGFR) was calculated by the CKD-EPI formula.Results(1) The levels of HIF-1α, RankL, hepcidin, and PTH were all elevated, and the serum ferritin and P³⁺ were elevated in each stage; (2) Linear correlation analysis: The HIF-1α and hepcidin showed a higher correlation with RankL in CKD3 and CKD4(CKD3: The correlation coefficient r = 0.558 between HIF-1α and RankL, and r = 0.604 between HEpcidin and RankL; CKD4: Correlation coefficient r = 0.840 between HIF-1α and RankL, and r = 0.753 between HEpcidin and RankL), while the PTH showed a higher correlation with RankL in CKD5 (correlation index r = 0.631). Multiple linear stepwise regression analysis: RankL was independently correlated with HIF-1α, hepcidin, and PTH. Regression coefficient B of HIF-1α was the highest in both CKD3 and CKD4. The coefficient B value of PTH in CKD5 was 3.971; HIF-1α and hepcidin were not included in the regression equation.ConclusionThe levels of RankL in both CKD3 and CKD4 were increased and mainly affected by HIF-1α, followed by hepcidin. Moreover, HIF-1α and PTH had a combined effect on the RankL level in CKD5, and PTH was the main influencing factor.     

Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes

BackgroundBorderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis.MethodsPatients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BL_D) and focal BL (BL_F) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACR_ND) (n = 12), biopsies with ACR and graft dysfunction (ACR_D) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated.ResultsThe primary composite outcome occurred in five patients of each of the Normal, BL_F and ACR_ND, eight patients with BL_D and six patients with ACR_D (p = 0.105). A trend towards more rejection episodes was observed in the ACR_ND and ACR_D. Also, a shorter time to rejection in the BL_D, ACR_ND and ACR_D groups compared to BL_F and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACR_ND group developed dnDSA, compared to 15–25% in the other groups. The median time of dnDSA development in the BL_F group was 45 months, and in the BL_D group was 10 months (p = 0.020).ConclusionClassifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BL_D with a phenotype that shows a trend towards worse outcomes, and BL_F that behaves more similar to normal biopsies.