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Summary: Most reports of risk factors (RF) for developing transplant‐associated thrombotic microangiopathy (TA‐TMA) and death are derived from paediatric and young adult cohorts, with minimal data on differences in RF and outcomes by age. In this secondary CIBMTR analysis, we used a previously prepared dataset that included all first allogenic haematopoietic cell transplantation (HCT) recipients with malignant or non‐malignant diseases between 2008 and 2016. The incidence of TA‐TMA 6 months post HCT was similar in children and adults 2.1% and 2.0% respectively. Grade 2–4 acute graft‐versus‐host disease (aGVHD) was a significant adjusted RF for developing TA‐TMA in both children and adults. In adults, additional adjusted RFs for TA‐TMA included female sex and black race, and in children an unrelated donor. Compared to a calcineurin inhibitor and sirolimus, other forms of GVHD prophylaxis had an adjusted decreased risk of developing TA‐TMA in adults. Adjusted RF for death in those with TA‐TMA (n = 652) included age ≥18 years old, early onset of TA‐TMA diagnosis (<100 days post HCT), grade 3–4 aGVHD and a performance score of <90 prior to HCT. In this cohort, the incidence of TA‐TMA was similar in children and adults, and TA‐TMA timing was a newly identified RF for death. [ABSTRACT FROM AUTHOR]

Summary: Allogeneic haematopoietic cell transplantation (allo‐HCT) remains an option for tyrosine kinase inhibitor‐resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high‐risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry‐based study of 1686 CML patients undergoing first allo‐HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo‐HCT was 46 years (IQR 36–55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse‐free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non‐relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft‐versus‐host disease (GvHD)‐free/relapse‐free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types. [ABSTRACT FROM AUTHOR]

Background and Objectives: ABO blood group mismatch between the donor and the recipient can affect the success of the transplant as well as problems with the red blood cells during allogeneic haematopoietic cell transplantation (HCT). However, the impact of the Rhesus (Rh) D mismatch on transplant outcomes in allogeneic HCT has been poorly elucidated. Materials and Methods: We retrospectively evaluated the impact of the RhD mismatch on post‐transplant outcomes in 64,923 patients who underwent allogeneic HCT between 2000 and 2021 using a Japanese registry database. Results: Out of the whole group, 64,293, 322, 270 and 38 HCTs were done when the recipient or donor was RhD‐mismatched with (+/+), (−/+), (+/−) or (−/−) combinations. The difference in RhD between recipient/donor (−/+), (+/−) and (−/−) did not affect haematopoietic recovery, acute and chronic graft‐versus‐host disease (GVHD), overall survival (OS), non‐relapse mortality (NRM) or relapse when RhD (+/+) was used as the reference group in multivariate analysis. Conclusion: Our registry‐based study demonstrated that RhD mismatch between recipient and donor did not significantly impact haematopoietic recovery, GVHD, OS, NRM or relapse after allogeneic HCT. These data suggest that RhD mismatches may not need to be avoided for recipient and donor combinations in allogeneic HCT. [ABSTRACT FROM AUTHOR]

Allogeneic hemopoietic cell transplantation remains the goal of therapy for high-risk acute myeloid leukemia (AML). However, treatment failure in the form of leukemia relapse or severe graft-versus-host disease remains a critical area of unmet need. Recently, significant progress has been made in the cell therapy-based interventions both before and after transplant. In this review, the Stem Cell Engineering Committee of the International Society for Cell and Gene Therapy summarizes the literature regarding the identification of high risk in AML, treatment approaches before transplant, optimal transplant platforms and measures that may be taken after transplant to ideally prevent, or, if need be, treat AML relapse. Although some strategies remain in the early phases of clinical investigation, they are built on progress in pre-clinical research and cellular engineering techniques that are already improving outcomes for children and adults with high-risk malignancies. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many bloodbased disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD. We applied a machine learning algorithm to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91. To test this classifier, we used an independent validation cohort (n = 288) selected using the same criteria as the discovery cohort. Attempts to validate the classifier failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort. Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use. [ABSTRACT FROM AUTHOR]

Simple Summary: Relapse following allogeneic hematopoietic stem cell transplantation (alloHSCT) for acute myeloid leukemia (AML) is the main reason for treatment failure. Most relapses occur during the first six months. We have observed in recent years that some patients relapse late, beyond 2 years after allograft. We sought to evaluate the frequency and the risk factors associated with these late relapses. We observed that these late relapses affect a significant number of patients, that the absence of chronic GvHD is more often associated. In addition, the intensity of the conditioning regimen does not seem to play a role and it is possible to re-treat successfully these patients. We conclude that prolonged monitoring after alloHSCT for AML is recommended. Late relapse, beyond 2 years following alloHSCT for AML, is rare. Among the 376 patients allografted for AML in our center between 1990 and 2016, 142 (38%) relapsed. The majority (68%) of relapses occurred during the first year following transplantation. Beyond 2 years after alloHSCT, relapse was observed in 26 patients, representing 6.9% of the whole transplanted cohort and 18.3% of the relapsing patients. Cytogenetics at relapse was available in 21 patients and remained for 15 of them concordant to that at diagnosis. The majority (85.7%) of the patients were in CR prior to transplant. Thirteen patients had grade 1–2 acute GvHD, while 13 other patients had grade 3–4 acute GvHD. None of these patients subsequently developed chronic GvHD. In multivariate analyses, a predictive factor of the absence of relapse 2 years after transplantation was the development of extensive chronic GVHD. Salvage therapy achieved new CR in 77% of these patients. We conclude that late relapse can affect a significant minority of patients allografted for AML, and the intensity of the conditioning regimen does not seem to have an impact on these relapses. Moreover, we were able to show that those patients can receive effective salvage therapy. [ABSTRACT FROM AUTHOR]

Summary: Haploidentical haematopoietic cell transplantation (haplo‐HCT) using post‐transplant cyclophosphamide (PTCY) as graft‐versus‐host disease (GVHD) prophylaxis is the standard of care for various haematological malignancies. The original PTCY dose after haplo‐HCT was 100 mg/kg, but no dose‐finding studies have been performed to identify the optimal dose. We performed a retrospective analysis to compare standard‐dose PTCY (100 mg/kg) with reduced‐dose PTCY (80 mg/kg): 969 in the standard‐dose group and 538 in the reduced‐dose group. As there was a significant difference between the two groups regarding patient and transplant characteristics, we performed propensity score (PS) matching. After PS matching, 425 patients in each group were included. The probabilities of 2‐year OS were 55.9% in the standard‐dose group and 47.0% in the reduced‐dose group (p = 0.36). The cumulative incidences of 2‐year non‐relapse mortality were 21.3% in the standard‐dose group and 20.5% in the reduced‐dose group (p = 0.55). There was no significant difference in the incidence of acute (grade II–IV 29.2% [95% CI, 24.9–33.6] vs. 25.3% [95% CI, 21.3–29.6]; grade III–IV 7.3% [95% CI, 5.1–10.0] vs. 6.6% [95% CI, 4.5–9.3]) or chronic GVHD. In conclusion, reduced‐ and standard‐dose PTCY were comparable in terms of major clinical outcomes. [ABSTRACT FROM AUTHOR]

Dermatologic complications are common following allogeneic hematopoietic stem cell transplantation, but dermatologic complications among pediatric patients undergoing hematopoietic stem cell transplantation for the treatment of sickle cell disease have been poorly characterized. In this case series of 17 patients (<21 years old) with sickle cell disease who underwent hematopoietic stem cell transplantation, 16 (94.1%) experienced one or more dermatologic complications after transplant, with the most common complications including acute or chronic mucocutaneous graft‐versus‐host disease (GVHD) (34.1% of complications), skin eruptions of unknown origin (15.9% of complications), infections (15.9% of complications), and chemotherapy‐related pigmentary changes (11.4% of complications). Patients who developed acute or chronic skin GVHD were significantly older at the time of hematopoietic stem cell transplantation. These findings highlight the need to closely monitor for dermatologic complications in pediatric patients who undergo hematopoietic stem cell transplantation for sickle cell disease and underscore the importance of involving dermatology early on when skin complications occur, although further research with a larger multicenter study could help clarify the risk for dermatologic complications and help identify potential ways to mitigate this risk. [ABSTRACT FROM AUTHOR]

Objectives: Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators. Materials and methods: A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored. Results: A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6–10.6) and SWS (OR: 8.2, 95% CI: 2.9–24.6). After 3 and 12 months, this effect was not statistically significant anymore. Conclusions: Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly. Clinical relevance: Because of the high prevalence of hyposalivation, HCT recipients will have an increased risk of oral complications. It might be reasonable to plan additional check-ups in the dental practice and consider additional preventive strategies. [ABSTRACT FROM AUTHOR]

This study investigated the impact of early cyclosporin A (CsA) initiation (day −5) on the risk of acute graft versus host disease (aGvHD) after allogeneic haematopoietic cell transplantation (allo-HSCT). Sixty-seven leukaemia patients who underwent allo-HSCT were investigated. The correlation between the CsA level in the first four weeks and the following indices was examined: GvHD, cumulative incidence (CI) of GvHD, CI of relapse at month 18, and non-relapse mortality (NRM) at month 18. A significant association between aGvHD and CsA level in the fourth week after allo-HSCT was observed, with the incidence of aGvHD in the fourth week in the lower level group being higher than that in the higher level group (p = 0.044). The CI of aGvHD was 30.1% and 9.8% at day +90 and 42.3% and 17.1% at day +180 in the lower level and higher level groups, respectively. For Chinese patients, early introduction and reaching the target CsA concentration within four weeks after allo-HSCT have a positive effect on preventing GvHD, especially in the fourth week after HSCT. Compared to the Western population, the target CsA concentration is lower and the time required to reach the target (within 4 weeks) is longer in the Chinese population (274.75 ng/mL). [ABSTRACT FROM AUTHOR]

Objectives: To estimate the incidence, risk factors, and outcome of cytomegalovirus (CMV) infection during the first year following hematopoietic stem cell transplant (HSCT) among Omani patients. Methods: This retrospective study included allogenic HSCT recipients between January 2006 and December 2018. We investigated the possible factors associated with CMV infection and CMV impact on one-year mortality. Results: Among 556 recipients of allogenic HSCT, 308 (55.4%) were male, the median age was 12 years, and 366 (65.8%) had benign conditions. One-year after transplants, the prevalence of CMV infection was 59.4%, and that of CMV disease was 1.8%. Multivariate analyses revealed significant relationships between CMV infection and haploidentical transplant (p = 0.006), graft versus host disease (p = 0.013), myeloablative conditioning (p = 0.001), and patient age ≥ 12 years (p < 0.001). CMV infection was associated with an increased risk of one-year mortality (p = 0.001). One-year overall mortality was 8.3%. Conclusions: The incidence of CMV infection in this Omani cohort was comparable with earlier findings, but the disease incidence and overall mortality were lower. Older age, haploidentical transplant, myeloablative conditioning, and graft versus host disease were significantly associated with a higher risk of CMV infection. In addition, CMV infection was associated with an increased risk of overall mortality in the first year post-transplant. Our findings support early initiation of preemptive therapy at low-level CMV viremia. [ABSTRACT FROM AUTHOR]

Aim: It is known that the prognosis of acute leukemia patients who relapse after the first allogeneic stem cell transplantation (ASCT) is dismal. Our goal was to assess the value of a second allogeneic stem cell transplant in acute leukemia patients who experienced post-transplant recurrence. Material and Methods: We retrospectively reviewed data from 29 patients with relapsing acute leukemia who underwent a second ASCT. Nineteen patients with acute myeloid leukemia and ten patients with acute lymphoblastic leukemia were included in the study. Results: Ten AML patients and 10 ALL patients were included in the study. Most patients (62%) were in remission before the second transplantation. The median time between the first and second ASCT was 11.9 months (3.1-42 months). Complete remission (CR) was achieved after the second ASCT in 21 (72%) patients, and 11 (52%) patients relapsed after the second ASCT. During this analysis, six patients (21%) were alive and in remission. Relapse of the disease was the leading cause of mortality. After the second ASCT, overall survival (OS) was 6.34 months, and leukemia-free survival (LFS) was 13.8 months. Conclusion: For patients with acute leukemia who relapsed after the first ASCT, a second ASCT is a good option and can keep patients alive. [ABSTRACT FROM AUTHOR]

Introduction: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live‐attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. Methods: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. Results: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤.0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft‐versus‐host disease (GVHD) did not affect the compliance with measles (p =.08) or YF vaccination (p =.7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p <.0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. Conclusion: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has emerged as a curative measure for life-threatening hematological disorders. It can be autologous or allogeneic depending on the disease characteristics. Providing transfusion support to the transplant patients can be challenging, especially in AB-mismatched allogeneic HSCT. In this study, we investigated the impact of ABO incompatibility in patients undergoing allogeneic HSCT. MATERIALS AND METHODS: A retrospective review was conducted in 76 patients with hematological diseases who underwent allogeneic HSCT. Transfusion requirements, engraftment profile, incidence of graft versus host disease (GvHD), and mortality for a period of 1 year were analyzed. RESULTS: ABO incompatibility between donor and the patient did not significantly affect the neutrophil and platelet (PLT) engraftment time (P = 0.389, 0.349, respectively), packed red blood cells transfusion requirement, and duration of initial hospital stay. However, patients of ABO-incompatible HSCT received more PLT transfusions posttransplant which was statistically significant. 29.1% of ABO compatible and 16.7% incompatible HSCT patients developed GVHD. Mortality rates in the two groups were 16.7% and 8.3%, respectively. However, differences in both the parameters were not statistically significant. CONCLUSION: Our study showed that ABO incompatibility does not significantly affect the outcome and should not be a limiting factor for selection of donor. Donor availability and human leukocyte antigen (HLA) matching remain the critical selection criteria. [ABSTRACT FROM AUTHOR]

Summary: Acute graft‐versus‐host disease (aGVHD) is a life‐threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first‐line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR‐GVHD are limited, and there is a significant unmet need for new non‐immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon‐like peptide 2 (GLP‐2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP‐2 treatment as a tissue regeneration approach and the potential use of the novel GLP‐2 analogue apraglutide as an adjunctive treatment for GI aGVHD. [ABSTRACT FROM AUTHOR]

Purpose: In the acute lymphoblastic leukemia (ALL) landscape, adolescents and young adults (AYA) often present high-risk diseases and increased chemotherapy-related toxicity. Studies analyzing the outcomes of AYA after hematopoietic stem cell transplantation (HSCT) are scarce. Our study aimed to compare the outcomes of children and AYA with ALL after HSCT and to determine the factors influencing potential differences. Method: 891 patients, from the SFGM-TC registry, aged between 1 and 25 years who received HSCT between 2005 and 2012 were included. The outcomes of AYA were compared to the ones of their younger counterparts. Results: Five-year OS and GRFS were lower in AYA: 53.1% versus 64% and 36% versus 47% (p = 0.0012 and p = 0.007, respectively). WhileCIR was similar in both groups, 5 year-treatment related mortality was higher in AYA: 19% versus 13% (p = 0.04). The lower GRFS in AYA was mainly explained by a higher chronic graft versus host disease (cGvHD) incidence: 32% versus 19% (p < 0.001). Use of peripheral blood stem cells and use of anti-thymoglobulin appeared to be the main factors impacting cGvHD occurrence in AYA. Conclusion: AYA have worse outcomes than children after HSCT for ALL because of a greater risk of TRM due to cGvHD. HSCT practices should be questioned in this population. [ABSTRACT FROM AUTHOR]

Summary: In a prospective, explorative study, the donor‐source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft‐versus‐host disease (GVHD) in HF‐HCT patients (49%, 7%, and 16% for HF‐, MS‐ and UD‐HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF‐HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri‐engraftment acute GVHD was not observed in MS‐HCT or UD‐HCT patients. Additionally, a significantly higher proportion of HF‐HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF‐, MS‐ and UD‐HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non‐relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG‐containing conditioning, stronger donor–patient alloreactivity was observed in HF‐HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism. [ABSTRACT FROM AUTHOR]

Introduction: A higher CD34+ cell dose in allografts is associated with faster haematopoietic recovery after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Leukaemia stem cells impair normal bone marrow (BM) niches and induce BM failure during leukemogenesis. However, whether measurable residual disease (MRD), known as the persistence of low‐level leukaemic cells, could influence the effects of CD34+ cell dose on haematopoietic recovery after transplantation in acute lymphoblastic leukaemia (ALL) patients is unknown. Methods: A total of 975 ALL patients were enrolled and classified into pre‐HSCT MRD‐positive and MRD‐negative subgroups. Cox proportional hazard regression models were built for time‐to‐event outcomes. Multivariate analysis was performed to determine independent influencing factors from the univariate analysis. Results: An appropriate CD34+ cell dose was positively associated with faster haematopoietic recovery in the total ALL population. More importantly, in pre‐HSCT MRD‐positive ALL patients, a higher CD34+ cell dose (≥2.76 × 106/kg) was related to faster neutrophil (HR 1.330, 95% CI 1.045–1.692, p = 0.021) and platelet engraftment (HR 1.808, 95% CI 1.412–2.316, p < 0.001) in multivariate analysis. CD34+ cell dose was a crucial factor associated with either engraftment or transplant outcomes, although we did not demonstrate direct correlations of CD34+ cell dose with relapse, TRM, LFS or OS after allo‐HSCT. Conclusion: Our results indicated that no additional CD34+ stem and progenitor cell harvests were needed to ensure successful haematopoietic recovery in pre‐HSCT MRD‐positive patients compared to pre‐HSCT MRD‐negative patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Hemato-poietic stem cell transplantation is associated with significant endothelial dysfunction, which may result in severe complications. Endothelial dysfunction induces the expression of multiple substances including, cell adhesion molecules, pro-inflammatory cytokines, and coagulation factors resulting in activation of the complement system, and promoting a procoagulant and proinflammatory state. The pathophysiological process that mediates the endothelial damage is not clearly understood and the aim of this study is a comprehensive review of the existing knowledge. Moreover, the levels of soluble molecules released in the systemic circulation as a result of endothelial damage may serve as biomarkers for the early diagnosis and the pre-emptive treatment of post-transplant syndromes. The review of the existing literature presented in detail shows that the ideal biomarker with sufficient sensitivity and specificity for the early diagnosis of post-transplant complications does not currently exist. Future studies should focus on the identification of novel biomarkers with sufficient specificity and sensitivity. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapy with a curative potential for a variety of malignant and non-malignant diseases. The major limitation of the procedure is the significant morbidity and mortality mainly associated with the development of graft versus host disease (GVHD) as well as with a series of complications related to endothelial injury, such as sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transplant-associated thrombotic microangiopathy (TA-TMA), etc. Endothelial cells (ECs) are key players in the maintenance of vascular homeostasis and during allo-HSCT are confronted by multiple challenges, such as the toxicity from conditioning, the administration of calcineurin inhibitors, the immunosuppression associated infections, and the donor alloreactivity against host tissues. The early diagnosis of endothelial dysfunction syndromes is of paramount importance for the development of effective prophylactic and therapeutic strategies. There is an urgent need for the better understanding of the pathogenetic mechanisms as well as for the identification of novel biomarkers for the early diagnosis of endothelial damage. This review summarizes the current knowledge on the biology of the endothelial dysfunction syndromes after allo-HSCT, along with the respective therapeutic approaches, and discusses the strengths and weaknesses of possible biomarkers of endothelial damage and dysfunction. [ABSTRACT FROM AUTHOR]

Bone marrow-derived hematopoietic stem cell transplantation/hematopoietic progenitor cell transplantation (HSCT/HPCT) is widely used and one of the most useful treatments in clinical practice. However, the homing rate of hematopoietic stem cells/hematopoietic progenitor cells (HSCs/HPCs) by routine cell transfusion is quite low, influencing hematopoietic reconstitution after HSCT/HPCT. The authors developed a micro-living motor (MLM) strategy to increase the number of magnetically empowered bone marrow cells (ME-BMCs) homing to the bone marrow of recipient mice. In the in vitro study, migration and retention of ME-BMCs were greatly improved in comparison with non-magnetized bone marrow cells, and the biological characteristics of ME-BMCs were well maintained. Differentially expressed gene analysis indicated that ME-BMCs might function through gene regulation. In the in vivo study, faster hematopoietic reconstitution was observed in ME-BMC mice, which demonstrated a better survival rate and milder symptoms of acute graft-versus-host disease after transplantation of allogeneic ME-BMCs. This study demonstrated that ME-BMCs serving as MLMs facilitated the homing of HSCs/HPCs and eventually contributed to earlier hematopoietic reconstitution in recipients. These data might provide useful information for other kinds of cell therapies. The authors performed hematopoietic stem/progenitor cell transplantation using magnetically empowered bone marrow cells (ME-BMCs) as a micro-living motor strategy. In vitro experiments showed that ME-BMCs can be manipulated under certain magnetic fields with little cytotoxicity. In vivo experiments showed that the ME-BMC strategy helped to achieve faster reconstitution in both autologous and allogeneic models. Transcriptome analysis indicated that ME-BMCs may function via not only physical forces but also gene regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Cytokine‐induced killer lymphocytes (CIK) are a promising alternative to conventional donor lymphocyte infusion (DLI), following allogeneic haematopoietic cell transplantation (HCT), due to their intrinsic anti‐tumour activity and reduced risk of graft‐versus‐host disease (GVHD). We explored the feasibility, anti‐leukaemic activity and alloreactive risk of CIK generated from full‐donor chimaeric (fc) patients and genetically redirected by a chimeric antigen receptor (CAR) (fcCAR.CIK) against the leukaemic target CD44v6. fcCAR.CIK were successfully ex‐vivo expanded from leukaemic patients in complete remission after HCT confirming their intense preclinical anti‐leukaemic activity without enhancing the alloreactivity across human leukocyte antigen (HLA) barriers. Our study provides translational bases to support clinical studies with fcCAR.CIK, a sort of biological bridge between the autologous and allogeneic sources, as alternative DLI following HCT. [ABSTRACT FROM AUTHOR]

Background: Human leukocyte antigen (HLA) molecules mediate critical roles in determining responsiveness or non-responsiveness of the immune system, especially in transplantation. Some studies have shown a possible association between certain HLA alleles and some allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes such as acute/chronic graft-versus-host disease (aGVHD/cGVHD) and overall survival (OS). In the current study, we investigated any possible association of HLA subclasses and acute/chronic GVHD occurrence as well as OS in patients receiving HLA-matched sibling allo-HSCT. Methods: We retrospectively evaluated the association of various HLA alleles with the incidence of aGVHD, cGVHD, and OS of 162 patients who received allo-HSCT from HLA-matched sibling between 2009-2018 at Taleghani hospital in Tehran. Results: We found that the incidence of aGVHD grades II-IV was higher among patients who had HLA-B*07 (P = 0.031) and HLADRB1*07 (P = 0.052). The presence of HLA-A*01 was associated with 4.5-fold greater odds of incidence in the extensive-type of cGVHD (P = 0.009). Furthermore, HLA-A*03 (P = 0.089), HLA-B*13(P = 0.013), HLA-B*40 (P = 0.042), HLA-DRB1*02 (P = 0.074), and HLA-DRB1*04 (P = 0.039) were associated with a lower rate of OS. Conclusion: This study suggests that certain HLA alleles might influence the incidence and severity of acute or chronic GVHD in the context of HLA-matched sibling allo-HSCT. In addition, some specific HLA alleles help predict OS in allo-HSCT recipients. These results might be helpful in estimating the incidence of aGVHD, cGVHD, and OS as well as designing personalized therapy. [ABSTRACT FROM AUTHOR]

Summary: Haematopoietic cell transplantation (HCT) is the only curative treatment for haematological complications in patients with Fanconi anaemia (FA). Haploidentical (haplo‐) HCT is a promising alternative for FA. We aimed to analyse the outcomes of unmanipulated haplo‐HCT in patients with FA with radiation‐free conditioning. A total of 56 patients from 11 centres between 2013 and 2021 in China were retrospectively analysed. The mean (SD) cumulative incidence was 96.4% (0.08%) for 30‐day neutrophil engraftment and 85.5% (0.24%) for 100‐day platelet engraftment. With a median (range) follow‐up of 2.4 (0.2–5.8) years, favourable mean (SD) overall survival of 80.9% (5.5%) and event‐free survival of 79.3% (5.6%) were achieved. The mean (SD) incidences of acute graft‐versus‐host disease (aGvHD) Grade II–IV and Grade III–IV were 55.4% (0.45%) and 42.9 (0.45%) respectively. The mean (SD) cumulative incidence of 3‐year chronic graft‐versus‐host disease (cGvHD) was 34.7% (0.86%) and that of moderate‐to‐severe cGvHD was 9.0% (0.19%). Our data demonstrate that in unmanipulated haplo‐HCT for patients with FA, radiation‐free regimens based on fludarabine and low‐dose cyclophosphamide ± busulfan achieved favourable engraftment and survival with relatively high incidences of aGvHD and cGvHD. These results prompt the use of low‐intensity conditioning without radiation and intensive GvHD prophylaxis when considering unmanipulated haplo‐HCT in patients with FA. [ABSTRACT FROM AUTHOR]

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The purpose of this retrospective study was to study the correlation between donor age (DA) and non-relapse mortality (NRM) and relapse incidence (RI) among patients treated with allogeneic hematopoietic cell transplantation (aHCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in a single Canadian center. Data from 125 consecutive patients transplanted with a matched related or unrelated donor between 2015 and 2020 were analyzed using multivariable models. After a median follow-up of 2.8 years, the cumulative incidences of NRM and relapse were 19% and 35% at 5 years. Despite being independently associated with NRM and relapse-free survival (RFS), DA was not associated with RI. The independent determinants of NRM in addition to DA were patient age and hematopoietic cell transplantation comorbidity index (HCT-CI), independently of donor kinship. The effect of DA on NRM was found to be significantly increased over the age of 50 years. DA was not associated with incidence of acute graft-versus-host disease (aGVHD) but showed an association with the occurrence of chronic GVHD (cGVHD). In conclusion, younger donors should be favored to limit NRM and increase RFS in HLA-matched aHCT. The etiological mechanisms behind the association of DA with higher NRM remain to be elucidated. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation treatment has been viewed as a therapeutic modality to enable the infusion of higher doses of chemotherapy to eradicate tumor cells. Nevertheless, recent reports have shown that, in addition to stem cells, infusion of autograft immune effector cells produces an autologous graft-versus-tumor effect, similar to the graft-versus-tumor effect observed in allogeneic-stem cell transplantation, but without the clinical complications of graft-versus-host disease. In this review, I assess the impact on clinical outcomes following infusions of autograft-antigen presenting cells, autograft innate and adaptive immune effector cells, and autograft immunosuppressive cells during autologous stem cell transplantation. This article is intended to provide a platform to change the current paradigmatic view of autologous stem cell transplantation, from a high-dose chemotherapy-based treatment to an adoptive immunotherapeutic intervention. [ABSTRACT FROM AUTHOR]

Patients were transplanted with a median time to allo-HCT of 15.1 months (IQR, 9.8-27.9) for CEL, NOS patients, and 22.2 months (IQR, 11.5-55.8; I p i = 0.01) for HES. Helbig et al. reported on 10 patients with CEL, NOS with a median age of 62 (23-73 years), frequently with an aggressive clinical course, five of whom developed acute transformation within two years from the time of diagnosis.6 Here, only one patient in the chronic phase successfully underwent allo-SCT. Keywords: allogeneic stem cell transplant; chronic eosinophilic leukaemia; conditioning; hypereosinophilic syndrome; non-relapse mortality EN allogeneic stem cell transplant chronic eosinophilic leukaemia conditioning hypereosinophilic syndrome non-relapse mortality 209 213 5 06/27/22 20220701 NES 220701 Hypereosinophilic syndrome (HES) and chronic eosinophilic leukaemia (CEL), not otherwise specified (NOS) are rare haematological disorders.1 Allogeneic haematopoietic cell transplantation (allo-HCT) has been reported in single case reports or small case series only for both refractory HES or CEL, NOS and outcomes remain ill-defined.1-3 HES normally demonstrates a male predominance, likely underrecognized, with a variable clinical course. [Extracted from the article]

Introduction: Granulocyte colony-stimulating factor (G-CSF) hastens neutrophil engraftment and reduces infections after allogeneic hematopoietic cell transplant (alloHCT), yet the optimal start date is unknown. Additionally, concurrent G-CSF and methotrexate for graft-vs-host disease (GVHD) prophylaxis may potentiate myelosuppression, and prolonged G-CSF is costly. Our institution changed from day + 4 to day + 12 G-CSF initiation following reduced intensity (RIC) alloHCT with methotrexate GVHD prophylaxis. Methods: We retrospectively compared day + 4 and day + 12 G-CSF initiation after RIC alloHCT from 2017–2021. The primary endpoint was the time to neutrophil engraftment. Secondary endpoints included length of stay (LOS) and the time to platelet engraftment as well as the incidence of infectious events, acute GVHD (aGVHD), and mucositis. Results: Thirty-two patients were included in each group with similar baseline characteristics. We observed faster neutrophil engraftment (median 12 vs. 15 days, p = 0.01) and platelet engraftment (median 13 vs. 15 days, p = 0.026) with day + 4 vs. day + 12 G-CSF initiation. Median LOS was 23 days (range, 19–32) with day + 4 initiation vs. 24 days (21–30) with day + 12 (p = 0.046). The incidence of culture-negative febrile neutropenia (p = 0.12), any grade aGVHD (p = 0.58), and grade 2-4 mucositis (p = 0.8) were similar between groups. Conclusion: Compared to day + 4, day + 12 G-CSF initiation following RIC alloHCT had a longer time to neutrophil and platelet engraftment. Day + 12 initiation also resulted in longer LOS, which while statistically significant, was potentially of limited clinical significance. These findings are hypothesis generating. [ABSTRACT FROM AUTHOR]

The gut microbiome is an important regulator of health and disease. The report by Hino et al. suggests that damage to the microbiome, inflicted before and soon after allogeneic haematopoietic progenitor cell transplantation, does not heal by itself, most likely with consequences for late transplantation outcomes. Commentary on: Hino et al. Prolonged gut microbial alterations in post‐transplant survivors of allogeneic haematopoietic stem cell transplantation. Br J Haematol 2023;200:725‐737. [ABSTRACT FROM AUTHOR]

Purpose: Allogeneic hematopoietic cell transplantation (alloHCT), also known as stem cell or bone marrow transplantation, is a cellular therapy performed to treat a variety of malignant and non-malignant hematologic diseases. Chronic graft-versushost disease (cGVHD) is a common immune-mediated complication of alloHCT that can affect various organs of the body, with approximately 70% of affected patients presenting with oral features. Oral manifestations of cGVHD include lichenoid lesions (diagnostic feature), erythema, pseudomembranous ulcerations, superficial mucoceles, salivary gland hypofunction, xerostomia, orofacial sclerosis, trismus, and increased sensitivity to spicy, acidic, hard, and crunchy foods. Patients with oral cGVHD are also at increased risk for developing secondary conditions, such as oral candidiasis, dental caries, and oral squamous cell carcinoma. Given these complex oral health challenges, the dental hygienist can play a key role in optimizing patients' oral health care from pre-stem cell transplantation through survivorship. Optimal care includes a comprehensive health history assessment, thorough extraoral and intraoral examinations, detailed hard and soft tissue evaluations, oral hygiene, and dietary assessment, along with the delivery of patient-centered, oral health instruction and preventive therapies. Appropriate monitoring and management of oral cGVHD require a collaborative care approach between dental, oncology, and oral medicine providers. As part of a multidisciplinary care team, dental hygienists play an important role in the management of patients with oral cGVHD. The purpose of this review is to provide an overview of alloHCT and its oral health considerations, with a focus on oral cGVHD etiology, signs and symptoms, and management considerations for the dental team. [ABSTRACT FROM AUTHOR]