Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.

Patients with acute myeloid leukemia (AML) who experience relapse following allogeneic hematopoietic cell transplantation (alloHCT) face unfavorable outcomes regardless of the chosen relapse treatment. Early detection of relapse at the molecular level by measurable residual disease (MRD) assessment enables timely intervention, which may prevent hematological recurrence of the disease. It remains unclear whether molecular MRD assessment can detect MRD before impending relapse and, if so, how long in advance.

Hepatic Artery Delineation on Ultrasound Volumes Comparing B-Flow and Color Doppler for Postoperative Monitoring of Pediatric Liver Transplants.

(1) Background: Accurate hepatic artery (HA) depiction following pediatric liver transplantation (LT) is essential for graft surveillance but challenging on ultrasound (US). This study assesses if improved HA delineation can be achieved by recording two-dimensional US volumes in Color Doppler (CD) and B-flow technique. (2) Methods: Of 42 consecutive LT, 37 cases were included, and HA delineation was retrospectively rated using a four-point score (0 = HA not detectable, 3 = HA fully detectable, separable from portal vein) within 48 h post-LT (U1) and before discharge (U2).

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

Background: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

Background: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available.

The graft-versus-leukemia effect of prophylactic donor lymphocyte infusions after allogeneic stem cell transplantation is equally effective in relapse prevention but safer compared to spontaneous graft-versus-host disease.

Therapeutic donor lymphocyte infusions (tDLI) are used to reinforce the graft-versus-leukemia (GvL) effect in relapse after allogeneic stem cell transplantation (alloSCT). In contrast, the role of prophylactic DLI (proDLI) in preventing leukemia relapse has been less clearly established, although supported by retrospective, case-control, and registry analyses. We report a prospective, monocentric, ten year cohort of patients with high risk acute leukemias (AL) or myelodysplasia (MDS) in whom proDLI were applied beyond day +120 post alloSCT to compensate for lack of GvL.

Spectral flow cytometry cluster analysis of therapeutic donor lymphocyte infusions identifies T cell subsets associated with outcome in patients with AML relapse.

Identification of immune phenotypes linked to durable graft-versus-leukemia (GVL) response following donor lymphocyte infusions (DLI) is of high clinical relevance. In this prospective observational study of 13 AML relapse patients receiving therapeutic DLI, we longitudinally investigated changes in differentiation stages and exhaustion markers of T cell subsets using cluster analysis of 30-color spectral flow cytometry during 24 months follow-up. DLI cell products and patient samples after DLI were analyzed and correlated to the clinical outcome.

Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis.

Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity.

Increased Late Noncardiac Nonrelapse Mortality in Patients with Atrial Fibrillation Diagnosed During Their Hospital Stay for Allogeneic Stem Cell Transplantation.

Atrial fibrillation (AF) is the most common arrhythmia in adults but its impact on allogeneic stem cell transplantation (SCT) is not well characterized. We studied AF manifestation during the hospital stay for allogeneic SCT, referred to as AF in hospital (AFiH), and analyzed the incidence of, risk factors for, and clinical impact of AFiH on intensive care unit (ICU)-/hospital-/ and overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). This retrospective matched cohort study comprised 553 consecutive SCT recipients at Hannover Medical School between January 2013 and October 2019.

Adaptive NK cells undergo a dynamic modulation in response to human cytomegalovirus and recruit T cells in in vitro migration assays.

Human cytomegalovirus (HCMV) reactivation remains a relevant complication after hematopoietic stem cell transplantation (HSCT) despite the great progress made in prophylaxis and treatment. Adaptive Natural Killer (NK) cells undergo a persistent reconfiguration in response to HCMV reactivation however, the exact role of adaptive NK cells in HCMV surveillance is currently unknown. We studied the relationship between HCMV reactivation and adaptive NK cells in 70 patients monitored weekly until day +100 after HSCT.

Acute onset of central diabetes insipidus during adolescent idiopathic scoliosis surgery.

This is a case report of a 12-year-old female with idiopathic scoliosis undergoing posterior scoliosis reconstruction that developed an acute onset of central diabetes insipidus (CDI) during surgery. The diagnosis was made as a result of an intraoperative increase in urine output to 6.82 ml/kg/hour (550 ml), a serum sodium increase from 139 to 147 mmol/L, a serum osmolality of 299 mOsmol/kg, a rapid response to vasopressin administration and a low vasopressin level of < 0.

B-Flow Sonography vs. Color Doppler Sonography for the Assessment of Vascularity in Pediatric Kidney Transplantation.

Objective:  To compare B-flow sonography (BFS) with color Doppler sonography (CDS) for imaging of kidney transplant vascularization in children.

Patients And Methods:  All children receiving a kidney transplantation who underwent a protocol-based ultrasound examination (Loqiq 9, GE Medical Systems, Milwaukee, WI, USA) using the BFS and CDS technique with equal settings and probe position between January 2013 and January 2016 were retrospectively assessed (n = 40). The obtained datasets were visually graded according to the following criteria: (I) delineation of the renal vascular tree (Grade 1 - clear demarcation of interlobar, together with arcuate and interlobular vessels; Grade 2 - clear demarcation of interlobar and cortical vessels, but no distinction of interlobular from arcuate vessels; Grade 3 - only clear demarcation of interlobar vessels, Grade 4 - insufficient demarcation) (II) delineation of cortical vessel density in ventral, lateral, and dorsal part of the transplant, (III) smallest vessel-capsule distance, and (IV) maximum cortical vessel count.

Cytomegalovirus-specific CD8+ T-cells are associated with a reduced incidence of early relapse after allogeneic stem cell transplantation.

Leukemia relapse is the main cause for mortality after allogeneic stem cell transplantation (allo-SCT). Donor-derived allo-immune responses eliminate the residual host hematopoiesis and protect against relapse. Cytomegalovirus (CMV) reactivation (CMV-R) after allo-SCT may trigger anti-leukemic effects.

Improved short- and long-term outcome of allogeneic stem cell recipients admitted to the intensive care unit: a retrospective longitudinal analysis of 942 patients.

Purpose: Intensive care unit (ICU) admission of allogeneic hematopoietic stem cell transplant (HSCT) recipients is associated with relatively poor outcome. Since longitudinal data on this topic remains scarce, we analyzed reasons for ICU admission as well as short- and long-term outcome of critically ill HSCT recipients.

Methods: A total of 942 consecutive adult patients were transplanted at Hannover Medical School from 2000 to 2013.

Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation.

Conventional analysis of host chimerism (HC) frequently fails to detect relapse before its clinical manifestation in patients with hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Quantitative PCR (qPCR)-based highly-sensitive chimerism analysis extends the detection limit of conventional (short tandem repeats-based) chimerism analysis from 1 to 0.01% host cells in whole blood.

Comparison of B-Mode with B-Flow Sonography for the Evaluation of Femoral Arteries in Infants.

 To evaluate femoral arteries (FAs) in infants in the context of catheter angiography with B-mode (BMS) and B-flow sonography (BFS) and to compare both methods for vessel delineation and reliability of vessel diameter measurements.  21 consecutive infants who underwent ultrasound for the evaluation of FAs before or after cardiac catheterization were retrospectively included in this study. The diameter of the FAs and the maximum length of the vessel section displayed on a single ultrasound plane were recorded by two radiologists for BMS and BFS.

Characterization of High-Avidity Cytomegalovirus-Specific T Cells with Differential Tetramer Binding Coappearing after Allogeneic Stem Cell Transplantation.

CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet CTLs) and high tetramer binding (CMV tet CTLs) in 53/115 CMV IgG patients stem cell transplanted from CMV IgG donors.

Possible Impact of Cytomegalovirus-Specific CD8 T Cells on Immune Reconstitution and Conversion to Complete Donor Chimerism after Allogeneic Stem Cell Transplantation.

Complete donor chimerism is strongly associated with complete remission after allogeneic stem cell transplantation (allo-SCT) in patients with hematologic malignancies. Donor-derived allo-immune responses eliminate the residual host hematopoiesis and thereby mediate the conversion to complete donor chimerism. Recently, cytomegalovirus (CMV) reactivation was described to enhance overall T cell reconstitution, to increase graft-versus-host disease incidence, and to reduce the leukemia relapse risk.

Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation is one curative treatment for hematological malignancies, but is compromised by life-threatening complications, such as severe acute graft-versus-host disease (aGvHD). Prediction of severe aGvHD as early as possible is crucial to allow timely initiation of treatment. Here we report on a multicentre validation of an aGvHD-specific urinary proteomic classifier (aGvHD_MS17) in 423 patients.

Expansion of recipient-derived antiviral T cells may influence donor chimerism after allogeneic stem cell transplantation.

Donor chimerism (DC) analysis is an important marker in the hematopoietic stem cell transplant follow-up. Here, we present evidence for a possible relationship of infectious complications and declines in DC. We analyzed the DC in patients experiencing cytomegalovirus (CMV) reactivation.

Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation.

Background: Reconstitution of cytomegalovirus-specific CD3(+)CD8(+) T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date.

Design And Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes.