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INTRODUCTION: In patients with acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) remains the priority treatment option as the most effective prevention of relapse. When an HLA-matched sibling is available, these transplants are preferred. OBJECTIVES: We stratificated patients according to risk, disease state (an active disease, the 1st or 2nd complete remission -- CR1, CR2, which was achieved after the 1st or 2nd induction) and type of graft (from brother or sister). Finally, the overall survival (OS) of patients in individual groups was evaluated. MATERIAL AND METHODS: The retrospective single-center study included 104 transplantations in 97 adult patients with AML who underwent HSCT from matched sibling donor in a period of 10 years between January 2011 and December 2020. RESULTS: 54 patients (55.7%) were alive as of the January 1, 2022. The median OS of the entire group, as well as the cohort with favorable (5y-OS 75.0%) and intermediate prognosis risk (5y--OS 78.5%) was not reached. We found that patients, who required second induction therapy to achieve CR, had poorer OS after allogeneic HSCT, median 20.7 months (95% CI, 6.5-35.5) than those who achieved CR after first induction, median not reached (95% CI, 63.5--63.5, p=0.0048). Statistically significant effect on OS shows transplantation in CR2 (HR 6.76, CI 95% 2.19--20.80, p=0.0009), In addition, this parameter influenced OS more than achieving CR up to the 2nd induction course (HR 2.44, CI 95% 1.17--5.11; p=0.0180) or entry to transplantation without CR (HR 2.81, CI 95% 1.09--7.26; p=0.0326). CONCLUSION: The results presented in the work show the high efficiency of HSCT in each risk group. The number of induction therapies required to achieve CR is a good prognostic factor. The gender of a sibling has no impact on OS [ABSTRACT FROM AUTHOR]

Abstract Background Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement. Methods We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC). Results Increased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760). Conclusion Our results suggest that uNAG is a promising biomarker for predicting IgAN remission status.

Background: Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement. Methods: We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC). Results: Increased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m2, area under the curve [AUC] 0.760). Conclusion: Our results suggest that uNAG is a promising biomarker for predicting IgAN remission status. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most common psychiatric disorders that accompany psychophysiological and mood changes. However, the pathophysiology-based disease mechanism of MDD is not yet fully understood, and diagnosis is also conducted through interviews with clinicians and patients. Diagnosis and treatment of MDD are limited due to the absence of biomarkers underlying the pathophysiological mechanisms of MDD. Although various attempts have been made to discover metabolite biomarkers for the diagnosis and treatment response of MDD, problems with sample size and consistency of results have limited clinical application. In addition, it was reported that future biomarker studies must consider exposure to antidepressants, which is the main cause of heterogeneity in depression subgroups. Therefore, the purpose of this study is to discover and validate biomarkers for the diagnosis of depression in consideration of exposure to drug treatment including antidepressants that contribute to the heterogeneity of the MDD subgroup. In the biomarker discovery and validation set, the disease group consisted of a mixture of patients exposed and unexposed to drug treatment including antidepressants for the treatment of MDD. The serum metabolites that differed between the MDD patients and the control group were profiled using mass spectrometry. The validation set including the remission group was used to verify the effectiveness as a biomarker for the diagnosis of depression and determination of remission status. The presence of different metabolites between the two groups was confirmed through serum metabolite profiling between the MDD patient group and the control group. Finally, Acetylcarnitine was selected as a biomarker. In validation, acetylcarnitine was significantly decreased in MDD and was distinguished from remission status. This study confirmed that the discovered acetylcarnitine has potential as a biomarker for diagnosing depression and determining remission status, regardless of exposure to drug treatment including antidepressants.

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN. [ABSTRACT FROM AUTHOR]

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Background: Acute myeloid leukemia (AML), the most common type of acute leukemia in adults, yet continues to have the lowest survival rate of all leukemias. The present study aimed to study ability of Day 14 marrow status to predict the remission status in AML. Materials and Methods: This prospective, observational study conducted in 30 AML patients who received "induction remission" as per standard guidelines and undergone bone marrow (BM) aspiration and biopsy on day 14 and day 28. Complete remission (CR) defined as per standard criteria. SPSS 15.3 was used to perform statistical analysis. Results: Median BM blast count on day14 was 10.6% (range, 1–50). Patients achieving remission in day 28 + BM had mean day 14 BM blast count of 8.52% compared to 21.00% in those who did not achieve remission. Majority (90.9%) of the patients with ≤15% BM blast on D14 was in remission. Comparing D14 BM blast% with CR, blast >15% cut off (across all the cut offs, i.e., 5%, 10%, 15%, or 20%) was the best to find those who entered remission; but the negative predictive value (NPV) was poor across all groups. Conclusions: There is a trend toward early relapse in patients with higher blast on D14. However, D14 BM marrow blast >15% has a poor NPV for predicting relapse. [ABSTRACT FROM AUTHOR]

The overall survival (OS) in patients with multiple myeloma (MM) has increased in the last decade due to the introduction of proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies as well as an extensive combination of autologous stem cell transplantation (ASCT) for suitable patients. The objective of this study was to examine the impact of pre-transplant and post-transplant remission status of patients on survival in newly diagnosed multiple myeloma. Two hundred and four patients with newly diagnosed MM who received an ASCT in our HSC transplant center at Hacettepe University Hospital between the years of 2001 and 2018 were evaluated in a retrospective manner. The median follow-up period was 35.9 months (range 4.2–206.4) for the entire group. The 5-year OS for pre-transplant remission status CR/VGPR patients and pre-transplant remission status PR or less patients were 79% and 68%, respectively (p = 0.09). The 5-year PFS for pre-transplant remission status CR/VGPR patients and pre-transplant remission status PR or less patients were 62% and 45%, respectively (p = 0.23). The 5-year OS for post-transplant remission status CR/VGPR group was 72% and for post-transplant remission status PR or less group was 60% (p = 0.02). The 5-year PFS in post-transplant remission status CR/VGPR patients was 48% and post-transplant remission status PR or less patients was 36% (p = 0.03). This study focuses on determination of survival outcome based on the best response obtained before and after ASCT and particularly highlights the significance of reaching CR and VGPR. [ABSTRACT FROM AUTHOR]

Purpose: Tumor volume in locally advanced head and neck squamous cell carcinomas (LAHNSCC) treated by induction chemotherapy (ICT) and followed by radiochemotherapy (RCT) was measured. The presence of potential correlation of initial tumor volume and volume reduction after ICT and RCT with remission status, overall survival (OS) and disease-free survival (DFS) were investigated. Furthermore, reliability of approximation of the tumor volume relying on its diameter to manual three-dimensional measurement was assessed.Methods: Data of patients with LAHNSCC treated by ICT consisting of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by definite RCT were retrospectively analyzed. The tumor volume was calculated slice-by-slice in contrast-enhanced CT or MRI before and after ICT as well as after complete treatment. The volume was compared to radiologic remission status, correlated with OS and DFS, and to volume estimation using tumor diameter.Result: 65 patients were included. Primary tumor volume did not correlate with complete remission rate (CR) after ICT and RCT, OS or DFS. The change in tumor volume between baseline imaging and post-RCT had a significant impact on OS (p = 0.026) and DFS (p = 0.028). The agreement between tumor volume and radiologic remission was 72.14%.Conclusion: The initial tumor volume had no influence on CR, OS or DFS. A severe response to ICT did not predict a powerful RCT outcome. The change in tumor volume post-RCT had an impact on OS and DFS. Tumor volume estimation using its diameter seems to be a reliable method. [ABSTRACT FROM AUTHOR]

Novel induction agents markedly improved remission rates in multiple myeloma (MM), and the continued use of chemotherapy for CD34 + stem cell mobilization (SCM) has been questioned. We examined the additional effect of chemotherapy in SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients (aged 36 to 75 years) with first autologous stem cell transplantation from January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured by changes in intact Ig and free light chain levels before and after chemomobilization (International Myeloma Working Group [IMWG] criteria). Most patients (225/236, 95.3%) received novel induction regimens, which were bortezomib-based (n = 223) and/or lenalidomide-based (n = 19). Most patients (170/190, 89.5%) achieved at least partial remission postinduction and pre-SCM. Stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide-based (212/227, 93.4%) or etoposide-based (15/227, 6.6%) regimens. There were insignificant changes in serum Ig and free light chain levels before and after chemomobilization either in the whole cohort or subgroups. Significant improvements of the IMWG remission status were documented in only 7 of 236 patients (3.0%). Sixty-seven patients (28.4%) developed chemotherapy-related complications (neutropenic fever, sepsis, and others), resulting in 9 hospitalizations (3.8%). Our study suggests that although causing significant morbidity, chemotherapy-based mobilization fails to improve remission status. The value of incorporating additional chemotherapy for SCM is thus not evident. [ABSTRACT FROM AUTHOR]

The outcome of allogeneic hematopoietic stem cell transplantation (HCT) in patients with myeloid malignancies is better in those without minimal residual disease (MRD) than in those with MRD+, as assessed by multiparametric flow cytometry (MPFC). WT1 quantitation also has been used to assess the probability of relapse in acute myelogenous leukemia (AML) treated with chemotherapy. We analyzed the clinical value of normalized bone marrow WT1 levels as a measure of the expanded myeloid progenitor compartment in a consecutive series of 193 adult patients with myeloid malignancies who underwent HCT. Bone marrow WT1 levels before the HCT, at the first bone marrow aspirate after infusion, and in the follow-up samples after HCT were determined by means of real-time PCR using the European LeukemiaNet normalized method. We sought to clarify the prognostic relevance in terms of overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR). Based on earlier experience in AML, we selected a threshold of 100 copies, defining 2 groups: patients with <100 WT1 copies and those with ≥100 copies. Patients with <100 WT1 copies before HCT (median time, 36 days; range, 4 to 268 days) had a better OS, PFS, and CIR than those with ≥100 copies (40 ± 1 versus 29 ± 6 days, P = .004; 35 ± 9 versus 26 ± 6 days, P = .002; and 29 ± 7 versus 37 ± 6 days, P = .051). In the first bone marrow study after the HCT (median time, 42 days; range 14 to 157 days, respectively), patients with <100 WT1 copies also had better outcomes in terms of OS, PFS, and CIR (40 ± 7 versus 31 ± 9 days, P = .025; 36 ± 7 versus 30 ± 8 days, P = .004; and 29 ± 6 days versus 54 ± 9, P  < .001, respectively). At this time point, bone marrrow samples with >100 copies also included patients who were negative for MRD as assessed by MPFC (19 of 32). During the HCT follow-up, patients with sustained WT1 levels <100 copies showed a marked benefit in terms of OS, PFS, and CIR even compared with those with only a single measurement >100 copies (mean, 68 ± 11 versus 26 ± 7 days, P  < .001; 63 ± 11 versus 20 ± 8 days, P  < .001; and 20 ± 8 vs. 71 ± 8 days, P  < .001, respectively). Standardized bone marrow WT1 levels using a 100-copy threshold in samples obtained before HCT, at leukocyte recovery, and during follow-up provided relevant prognostic information in patients with myeloid malignacies submitted to HCT. [ABSTRACT FROM AUTHOR]

Relapse of hematological malignancies after hematopoietic stem cell transplantation (HCT) is associated with poor prognosis. A second HCT represents one of the few therapeutic options for these high-risk patients. For children undergoing second HCT, the outcome data are particularly limited. We, therefore, conducted a retrospective single-institution study and report the outcomes and prognostic variables associated with overall survival (OS) and relapse in 43 pediatric patients who underwent a second HCT between 2000 and 2013. Eleven of the 43 patients who underwent transplantation remain alive and disease-free at a median follow-up of 49 months (range, 5 to 127 months). The 5-year probability of OS for the entire cohort was 24%. Patients who had early relapse (<6 months) after first HCT had significantly worse OS than those who relapsed late (>6 months), with 5-year OS at 11% versus 34%, respectively (hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.21 to 4.93; P = .013). Active disease at time of second HCT was also associated with a significantly increased risk of relapse (subdistribution hazard ratio [SHR], 2.36; P = .049) for the entire cohort and relapse was the most frequent cause of death (23 of 32; 72%). On subgroup analysis for the 34 patients with leukemia alone, presence of active disease was associated both with a significant decrease in OS (SHR, 2.28; 95% CI, 1.02 to 5.09; P = .044) and significant increase in the rate of relapse (SHR, 2.46; P = .046). By contrast, underlying disease, donor source, conditioning regimen, or development of GVHD did not modify OS or rate of relapse. Hence, a second HCT appears to be a useful therapeutic option in children with relapsed hematological malignancies that is most likely to benefit those individuals with late onset of relapse and with low disease burden at the time of transplantation. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most common psychiatric disorders that accompany psychophysiological and mood changes. However, the pathophysiology-based disease mechanism of MDD is not yet fully understood, and diagnosis is also conducted through interviews with clinicians and patients. Diagnosis and treatment of MDD are limited due to the absence of biomarkers underlying the pathophysiological mechanisms of MDD. Although various attempts have been made to discover metabolite biomarkers for the diagnosis and treatment response of MDD, problems with sample size and consistency of results have limited clinical application. In addition, it was reported that future biomarker studies must consider exposure to antidepressants, which is the main cause of heterogeneity in depression subgroups. Therefore, the purpose of this study is to discover and validate biomarkers for the diagnosis of depression in consideration of exposure to drug treatment including antidepressants that contribute to the heterogeneity of the MDD subgroup. In the biomarker discovery and validation set, the disease group consisted of a mixture of patients exposed and unexposed to drug treatment including antidepressants for the treatment of MDD. The serum metabolites that differed between the MDD patients and the control group were profiled using mass spectrometry. The validation set including the remission group was used to verify the effectiveness as a biomarker for the diagnosis of depression and determination of remission status. The presence of different metabolites between the two groups was confirmed through serum metabolite profiling between the MDD patient group and the control group. Finally, Acetylcarnitine was selected as a biomarker. In validation, acetylcarnitine was significantly decreased in MDD and was distinguished from remission status. This study confirmed that the discovered acetylcarnitine has potential as a biomarker for diagnosing depression and determining remission status, regardless of exposure to drug treatment including antidepressants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lee, Mun, Lee, Choi, Joo, Kang and Lee.)