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ABSTRACT Thymoma‐associated multiorgan autoimmunity (TAMA) is a rare paraneoplastic disorder that presents similarly to graft versus host disease (GVHD). We report a unique case of TAMA presenting as a GVHD‐like erythroderma in an elderly male with a history of benign thymoma. Cutaneous histopathological findings demonstrated vacuolar interface dermatitis with numerous dyskeratotic keratinocytes, exocytosis of lymphocytes, and a mildly acanthotic epidermis, which can be seen in several different disease processes. Thus, careful consideration of clinical presentation, historical information, laboratory testing, and histopathologic findings led to the correct diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Anti‐thymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis is widely used for mismatched unrelated donor allogeneic hematopoietic cell transplantation (HCT) although optimal dose remains unclear. Although recent literature suggested improved outcomes with PTCy‐based regimens when compared to ATG‐based regimens these studies used doses of ATG ≥5 mg/kg. Thus, we analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower‐dose ATG‐based regimens at our center. Methods: We retrospectively analyzed outcomes of HLA 9/10 MMUD allogeneic HCTs using lower dose ATG‐based regimens for all adults undergoing allogeneic HCT at The Ottawa Hospital from 2015 to 2022. Data regarding demographics, conditioning regimen, dose of ATG, rates of GVHD, duration of remission, and survival, were collected and analyzed. Results: Seventy‐seven (n = 77) patients (males 62.3%; median age 50 years) underwent allogeneic HCT from MMUD. Majority(81%; n = 63) received 2.5 mg/kg of rabbit ATG and remaining 18.2% (n = 14) received 4.5 mg/kg. Grade II‐IV acute GVHD occurred in 24.7% (n = 19) while any chronic GVHD occurred in 32.5% (n = 25) patients. After a median follow‐up of 21 months, relapse occurred in 28.6% of patients. Two‐year OS, GRFS, CIR, and NRM were 60.6%, 45.3%, 16.9%, and 18.2% respectively. Dose of ATG (2.5 mg/kg vs. 4.5 mg/kg) was not associated with outcomes in either univariate or multivariate analyses. Conclusions: When compared to published studies using ATG doses ≥5 mg/kg, GVHD prophylaxis using lower dose ATG may potentially lead to improved outcomes in patients undergoing MMUD allogeneic HCT. Further studies are needed to directly compare lower dose ATG to PTCy‐based regimens to determine ideal GVHD prophylaxis for these patients. [ABSTRACT FROM AUTHOR]

Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well‐established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC0–12 in Chinese patients undergoing allogeneic HSCT (allo‐HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC0–12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC0–12 (r2 < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC0–12 (r2 > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC0–12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12‐h period could effectively estimate MPA AUC0–12 with precise results and minimal bias. [ABSTRACT FROM AUTHOR]

This article discusses a rare occurrence of vaccine-derived rubella virus (VDRV) triggering granulomata in an adult patient who had a stem cell transplant. Rubella is an infection caused by a virus transmitted through respiratory secretions, but the vaccine has eliminated it in many countries. However, in some cases, VDRV can cause granulomata in individuals with weakened immune systems. The article emphasizes the need for more research on the public health implications of this phenomenon and the lack of effective treatments for persistent rubella infection. It also highlights the importance of MMR vaccination after stem cell transplants to restore immunity. The risks and benefits of live virus vaccination in immunocompromised individuals are still uncertain, and further research is necessary to understand the role of rubella and its vaccine in the development of other diseases. [Extracted from the article]

This article discusses the case of a 5-year-old girl with Nijmegen breakage syndrome (NBS), a genetic disorder characterized by microcephaly, chromosomal instability, and immunodeficiency. The patient experienced granulomatous lesions on her skin, which progressed despite treatment with corticosteroid and pimecrolimus creams. Due to severe immunodeficiency and progressing granulomatous lesions, the patient underwent hematopoietic stem cell transplantation (HSCT), which resulted in the resolution of the skin lesions and improvement in immune function. However, the patient later developed a high-grade B-cell lymphoma, which was treated with rituximab and donor lymphocyte infusions. At the last follow-up, the patient was in good clinical condition with remission of lymphoproliferation and regression of skin and splenic lesions. The study suggests that HSCT can be an effective treatment for severe immunodeficiency in NBS patients and may also benefit those with non-infectious immune complications caused by immune dysregulation. [Extracted from the article]

Posttransplantation complications pose a major challenge to the long‐term survival and quality of life of organ transplant recipients. These complications encompass immune‐mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft‐versus‐host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients. [ABSTRACT FROM AUTHOR]

Summary Modalities and timing of haematopoietic stem cell transplant (HSCT) in patients with GATA2 deficiency are still subject to debate. On June 2022, 67 patients (median age 20.6 years) underwent a first allogeneic HSCT among 21 centres. Indications for HSCT were myelodysplastic syndrome (MDS) ≤5% blasts ± immunodeficiency (66%), MDS >5% blasts (15%), acute myeloid leukaemia (19%). Conditioning regimen was myeloablative in 85% and anti‐thymocyte globulins were used in 67%. The cumulative incidence (CInc) of acute graft versus host disease (GvHD) grade II–IV and III–IV at day 100 were 42% and 13%, and CInc of chronic and extensive chronic GvHD at 2 years were 42% and 23%. CInc of relapses was 3% and 11% at 1 and 5 years. Overall survival (OS) at 1 and 5 years was 83% and 72% (median follow‐up 5.6 years). The factors associated with worse OS in multivariable analysis were the year of HSCT, a history of excess blasts before transplant and peripheral blood stem cell (PBSC) grafts. Age at HSCT, non‐myeloablative conditioning and PBSC grafts were associated with increased non‐relapse mortality. In conclusion, bone marrow monitoring to identify clonal evolution and perform HSCT before the appearance of excess blast is mandatory. [ABSTRACT FROM AUTHOR]

Summary: The global pandemic has resulted in the common occurrence of SARS‐CoV‐2 infection in the population. In the post‐pandemic era, it is imperative to understand the influence of donor SARS‐CoV‐2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). We retrospectively analysed allo‐HSCTs from donors with mild SARS‐CoV‐2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo‐HSCT from donors without prior SARS‐CoV‐2 infection as group 0 (n = 194). Transplants from donors with different SARS‐CoV‐2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft‐versus‐host disease (aGvHD), grade II–IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III–IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II–IV (hazard ratio [HR] 2.307, p = 0.010) and grade III–IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS‐CoV‐2 infection were associated with higher incidences of aGvHD in transplants from related donors. [ABSTRACT FROM AUTHOR]

Background: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft‐versus‐tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti‐cancer immune response. Methods: We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI‐free approach consisting of post‐transplant cyclophosphamide (PTCy) and short‐term Everolimus after reduced‐intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD. Results: Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow‐up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD‐relapse‐free‐survival was 47% after 3 years. Conclusions: Using PTCy and short‐term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non‐relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies. [ABSTRACT FROM AUTHOR]

Summary: This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan‐based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty‐two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first‐ or second‐generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1‐guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second‐year post‐transplant. All patients engrafted. The 1‐year transplant‐related mortality was 3% (confidence interval [CI]: 0%–6%). After a median follow‐up of 6.3 years, 5‐year overall survival and event‐free survival are 97% (CI: 93%–100%) and 91% (CI: 79%–100%) respectively. The current 5‐year leukaemia‐free survival with BCR::ABL1 <0.01% is 97% (CI: 88%–100%) and the current TKI‐ and DLI‐free survival is 95% (CI: 85%–100%). The incidence of chronic graft‐versus‐host disease (GvHD) was 32%, being severe in four patients (13%). At last follow‐up, 31 patients are GvHD‐free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP‐CML with an excellent disease‐free and TKI‐free survival. [ABSTRACT FROM AUTHOR]

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]

A remarkably high rate of post‐transplant relapse in patients with TP53‐mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT (N = 38) versus non‐HSCT (N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non‐HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion (p <.01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non‐HSCT) had multi‐hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non‐HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow‐up was 15.1 months for HSCT and 5.7 months for non‐HSCT. Median disease‐free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non‐HSCT cohorts, respectively. Non‐relapse mortality at 12 months was 22% versus 44% for HSCT versus non‐HSCT. In the HSCT cohort, the rate of grade II–IV acute and chronic graft‐versus‐host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non‐HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53‐mutated MDS/AML remain an area of unmet clinical need. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft‐versus‐host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft‐versus‐host disease (oGVHD). A 35‐year‐old female with a history of acute myeloid leukemia‐M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high‐intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long‐term benefits and mechanisms of OIH in oGVHD management. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life‐threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow‐derived mesenchymal stem cell (BM‐MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM‐MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft‐versus‐host disease, and renal insufficiency. Allogeneic BMT is a high‐risk procedure with possible benefits and adverse events. BM‐MSCs revealed favorable outcomes to improve the safety of EB cell‐based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment's long‐term effects and clarify the risk/benefit ratio of procedure versus conventional therapy. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo‐HSCT is associated with significant complications. The most common and debilitating among them is graft‐versus‐host disease (GVHD). In GVHD, donor‐derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD‐targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non‐lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF‐cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF‐A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF‐A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD‐targeted organs in vivo. We identified LFA‐1 (αLβ2) as the binding site of VWF on T cells. Our results showed that blocking T‐cell homing by ADAMTS13 or VWF‐A2 peptide reduced the severity of the GVHD after allo‐HSCT, a potentially novel method for treating and preventing GVHD. [ABSTRACT FROM AUTHOR]

Cyclosporin A is a well‐established immunosuppressive drug used to treat or prevent graft‐versus‐host disease, the rejection of organ transplants, autoimmune disorders, and leukemia. It exerts its immunosuppressive effects by inhibiting calcineurin‐mediated dephosphorylation of the nuclear factor of activated T cells (NFAT), thus preventing its nuclear entry and suppressing T cell activation. Here we report an unexpected immunostimulatory effect of cyclosporin A in activating the mammalian target of rapamycin complex 1 (mTORC1), a crucial metabolic hub required for T cell activation. Through screening a panel of tool compounds known to regulate mTORC1 activation, we found that cyclosporin A activated mTORC1 in CD8+ T cells in a 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) and protein kinase B (PKB/AKT)‐dependent manner. Mechanistically, cyclosporin A inhibited the calcineurin‐mediated AKT dephosphorylation, thereby stabilizing mTORC1 signaling. Cyclosporin A synergized with mTORC1 pathway inhibitors, leading to potent suppression of proliferation and cytokine production in CD8+ T cells and an increase in the killing of acute T cell leukemia cells. Consequently, relying solely on CsA is insufficient to achieve optimal therapeutic outcomes. It is necessary to simultaneously target both the calcineurin‐NFAT pathway and the mTORC1 pathway to maximize therapeutic efficacy. [ABSTRACT FROM AUTHOR]

This article discusses a case of graft-versus-host disease (GVHD) in the central nervous system (CNS) after allogeneic transplantation. GVHD in the CNS is a rare manifestation of chronic GVHD and its diagnosis is still controversial. The article presents a case study of a patient who developed CNS-GVHD after a stem cell transplant. The diagnosis was confirmed through microsatellite analysis using laser capture microdissection (LCM), which showed donor-derived CD8-predominant T-cell infiltration in the brain lesions. The patient was treated with glucocorticoids, mycophenolate mofetil (MMF), and ibrutinib, which resulted in improvement of symptoms and resolution of brain lesions. Further research is needed to validate this diagnostic method and explore optimal treatment strategies for CNS-GVHD. [Extracted from the article]

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]

Introduction: Cyclosporine‐A (CsA) and post transplantation cyclophosphamide (PTCy) are common agents used for graft versus host disease (GVHD) prophylaxis in Haploidentical hematopoietic cell transplantation (haplo‐HCT). However, the impact of CsA cessation timing in the posttransplant setting on clinical outcomes is uncertain. We aimed to investigate the impact of a novel approach that integrated early CsA cessation with PTCy utilization. Patients and Methods: This study was a single arm retrospective study carried out at a tertiary referral hospital hematology and bone marrow transplantation center between 2009 and 2022. The patients who received haplo‐HCT with ATG, PTCy and CsA as GVHD prophylaxis were included. CsA was planned for cessation starting at day 45 to day 60. Acute and chronic GVHD were evaluated and graded. CsA blood concentrations and its impact on acute and chronic GVHD was evaluated. Results: Thirty‐one patients composed of 19 (61.3%) male and 12 (38.7%) female patients with a median age of 31 years (20–58). Busulfan and TBI based conditioning regimens were the most utilized regimens. The majority of donors were first degree relatives. Stem cell origin was peripheral blood for all patients. GVHD prophylaxis consisted of ATG, CsA and PTCy. Acute GVHD was observed in 9 (29%) cases, whereas chronic GVHD was seen in 3 (9.7%) cases, with 2 of them having overlapping GVHD. Age, gender, number of chemotherapy lines, transplant characteristics, infused CD34 cell count, and engraftment durations were similar among patients with and without GVHD. Patients with GVHD had similar 1st, 2nd, 3rd and 4th week CsA concentrations compared to patients without GVHD (p > 0.05). The presence of GVHD was not associated with worse progression free survival and overall survival (p = 0.6, p = 0.5, respectively). CMV reactivation was more common in the GVHD group. Conclusion: In the current study, we did not find an impact of CsA concentration on GVHD and post‐transplant outcomes in Haplo‐HCT setting. Therefore, together with the use of PTCy, early CsA cessation can be an option; further studies are needed to understand all aspects of this approach. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus infection (CMV) is a common complication after allogeneic hematopoietic stem cell transplantation (AHSCT). CMV infection increases transplantation costs; however, the extent of the financial burden may vary in different countries. This study aims to determine the clinical and economic impact of CMV infection in patients undergoing AHSCT in a middle‐income country. Methods: A total of 150 adult and pediatric patients post‐AHSCT were included for analysis. In addition to incidence of CMV infections, data on graft versus host disease (GVHD) were also collected. Standard hospital charges for AHSCT and any additional transplantation‐related expenditure within 12 months were also retrieved in 104 patients. Results: CMV infection, acute GVHD and chronic GVHD occurred in 38.7%, 60.7%, and 22.0% of patients, respectively. Patients with CMV infections had higher readmission rates compared to those who did not (67.2% vs. 47.8%; p = 0.020). Additional expenditure was seen in HLA‐haploidentical AHSCT and CMV infection (MYR11 712.25/USD2 504.49; p < 0.0001 and MYR5 807.24/USD1 241.79; p = 0.036), respectively. Conclusion: This single‐center study demonstrated that patients who underwent HLA‐haploidentical AHSCT and subsequently developed CMV infection had higher transplantation expenditures compared to those who had matched‐related transplantation. Further studies should be conducted to evaluate if primary prophylaxis against CMV is cost‐effective, especially in patients who undergo HLA‐haploidentical AHSCT. [ABSTRACT FROM AUTHOR]

Background: There are currently no laboratory tests that can accurately predict the likelihood of developing acute graft‐versus‐host disease (aGVHD), a patient's response to treatment, or their survival chance. This research aimed to establish circulating miRNAs as diagnostic, prognostic, or predictive biomarkers of aGVHD. Methods: In a prospective cohort, we studied the incidence of cutaneous aGVHD in AML patients undergoing allo‐HSCT at Shariati Hospital in Tehran, Iran during 2020–2023. Patients with cutaneous aGVHD were labeled as the case group, while patients without cutaneous aGVHD were selected as the control group. Accordingly, the expression levels of six significant miRNAs (miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, miR‐548a‐3p) were evaluated by quantitative reverse transcription–polymerase chain reaction (RTqPCR) in three different time‐points: before transplantation, on day 14 and day 21 after transplantation. Results: The levels of plasma miR‐455‐3p, miR‐5787, miR‐638, and miR‐3613‐5p were significantly downregulated, while miR‐548a‐3p, and miR‐6511b‐5p were significantly upregulated in individuals with cutaneous aGVHD in comparison to patients without GVHD. Additionally, the possibility for great diagnostic accuracy for cutaneous aGVHD was revealed by ROC curve analysis of differentially expressed miRNAs (DEMs). Conclusion: The study findings encourage us to hypothesize that the aforementioned miRNAs may contribute to the predominance of aGVHD, particularly low‐grade cutaneous aGVHD. [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]

Background: CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2–4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target. Study design and Methods: In this retrospective, single‐center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft‐versus‐host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes. Results: There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85–1.22), relapse (aRR = 1.10, 95% CI = 0.85–1.42), or overall survival by Kaplan–Meier analysis (p =.44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II–IV, aRR = 1.18 grades III–IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 =.073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132). Discussion: We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction. [ABSTRACT FROM AUTHOR]

This article provides information on the use of solvent/detergent-treated plasma (S/D plasma) in transfusion medicine. S/D plasma is a type of plasma preparation that has been treated to improve safety by inactivating pathogens. It discusses the characteristics, efficacy, and safety of S/D plasma, particularly OctaplasLG, which is a frozen plasma preparation used as an alternative to fresh frozen plasma (FFP). Studies have shown that OctaplasLG is effective and has a good safety profile, with lower incidences of adverse reactions compared to FFP. It is recommended for various indications, including coagulation factor deficiencies, massive transfusion, and therapeutic plasma exchange. OctaplasLG has been found to be cost-effective and has been adopted by several European countries. It also has potential benefits in treating other medical conditions and protecting the endothelium. Overall, OctaplasLG is an effective and well-tolerated alternative to FFP, with expanding clinical utility and potential for improving patient outcomes. [Extracted from the article]

This article discusses a rare case of coexisting lichen planus (LP) and bronchiolitis obliterans (BO) without malignant tumors. LP is a chronic inflammatory disease that affects the skin, nails, hair, and mucous membranes, while BO is a progressive airway disorder characterized by narrowing and obliteration of the airway lumen. The patient in this case study experienced symptoms of LP, such as stomatitis and rash, followed by respiratory symptoms and was eventually diagnosed with CB, a subtype of BO. Despite treatment, the patient's respiratory condition worsened, and she died from respiratory failure. The relationship between LP and BO is not well understood, and more research is needed to establish effective therapeutic options for LP patients. [Extracted from the article]

Background: Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative treatment for hematological malignancies. Several complications following allo‐HSCT, such as graft‐versus‐host disease, infection, and malnutrition, often cause physical dysfunction, and the assessment of physical function and evaluation of muscle mass are incompletely performed. Use of ultrasound (US) allows muscle mass measurement in patients with poor general conditions. In allo‐HSCT recipients, the correlation between physical function and muscle thickness, as measured by US, remains unclear. Objective: To clarify whether muscle thickness measured by US correlated with physical function in allo‐HSCT recipients. Design: A single‐center prospective cohort study. Setting: Hospital. Patients: Ninety‐two patients underwent allo‐HSCT at our hospital from April 2017 to March 2019. Interventions: Not applicable. Main Outcome Measure(s): Biceps and quadriceps muscle thickness measured by US, grip strength, isometric muscle strength (elbow flexion and knee extension), and 6‐minute walking test (6MWT) before allo‐HSCT and on days 30, 90, 180, 1 year, and 2 years after allo‐HSCT. The implementation rates of these assessments were also investigated. Results: Correlations were observed between biceps thickness and elbow flexion muscle strength/grip strength before allo‐HSCT, on days 30, 90, 180, 1 year, and 2 years after allo‐HSCT (r = 0.71/0.74, 0.73/0.72, 0.70/0.79, 0.67/0.75, 0.72/0.75, and 0.85/0.79, respectively, all p <.001). At the same time points, quadriceps thickness moderately correlated with knee extensor strength (r = 0.49, 0.50, 0.45, 0.64, 0.61, and 0.58, all p <.001). However, biceps and quadriceps thicknesses did not correlate with the 6MWT. The percentages of patients measured with US and 6MWT were 93.4% and 82.4% (p =.01) on day 30 and 97.5% and 87.8% (p =.02) on day 90, respectively. Conclusions: US assessment may be a useful alternative method for estimating muscle strength in fragile allo‐HSCT recipients, particularly when physical function assessment is difficult to quantify. [ABSTRACT FROM AUTHOR]

This study sought to compare the behavior of Treg subsets displaying different coexpression patterns of Neuropilin‐1 (Nrp1) and Helios, under the influence of gut stress unrelated to hematopoietic stem cell transplantation, pretransplantation conditioning, and posttransplant gastrointestinal acute graft versus host disease (GI‐aGvHD). Host CD4+/CD25hi/Foxp3+ Treg cells, identified by flow cytometry, were isolated from various tissues of mice affected by these stressors. Expression of CD25, CTLA‐4, CD39, OX40, integrin‐β7, LAG3, TGFβ/LAP, granzyme‐A, ‐B, and interleukin‐10 was compared in four Treg subsets displaying Helios or Nrp1 only, both or none. Fluorescence‐activated cell sorter–sorted Treg subsets, displaying markers affected in a conditioning‐ and GI‐aGVHD‐restricted manner, were further investigated by transcriptome profiling and T‐cell suppression assays. We found that conditioning by irradiation greatly diminished the relative frequency of Helios+/Nrp1+ Treg, shifting the balance toward Helios−/Nrp1− Treg in the host. Upregulation of integrin‐β7 and OX40 occurred in GI‐aGvHD‐dependent manner in Helios+/Nrp1+ cells but not in Helios−/Nrp1− Treg. Sorted Treg subsets, confirmed to overexpress Nrp1, Helios, OX40, or integrin‐β7, displayed superior immunosuppressive activity and enrichment in activation‐related messenger RNA transcripts. Our data suggest that conditioning‐induced shrinkage of the Nrp1+/Helios+ Treg subset may contribute to the development of GI‐GvHD by impairing gut homing and decreasing the efficiency of Treg‐mediated immunosuppression. [ABSTRACT FROM AUTHOR]

This article discusses the future of immunology in Europe, with a focus on early-career researchers. It highlights the work of 16 young immunologists who presented their research at a symposium and were invited to write reviews on various topics in immunology. The article explores advancements in high-throughput technologies that have improved our understanding of immunity, the study of cellular dynamics and heterogeneity in immune regulation, and recent progress in immunotherapy and vaccine development. The authors emphasize the potential of these advancements to enhance disease prevention and treatment. The article also discusses recent advances in proteomics technologies and multi-omics studies related to tuberculosis, the importance of coenzyme A (CoA) homeostasis in disease, and recent developments in adjuvant design for vaccines. It concludes by highlighting the need to improve our understanding of traditional and modern vaccine development strategies. [Extracted from the article]

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare systemic disorder that affects patients with a history of thymoma. This systematic review summarizes the scientific evidence on TAMA skin manifestations, including epidemiology, clinical characteristics, treatments, and outcomes. The review analyzed 47 cases of TAMA, with skin involvement being the most frequent manifestation. Treatment options for TAMA skin manifestations include thymoma-directed therapies, corticosteroids, immunosuppressive drugs, and phototherapy. However, the prognosis for TAMA is poor, with a high mortality rate, often due to infections. Dermatologists should be aware of TAMA in patients with a history of thymoma. [Extracted from the article]

Introduction: Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post‐transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution. Methods: Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non‐relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed. Results: The median follow‐up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non‐relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962). Conclusion: Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan. Herein, we describe the outcomes and compare results of patients who underwent matched and haploidentical allogeneic hematopoietic stem cell transplantation (HSCT) with treosulfan based or busulfan based reduced intensity, non‐myeloablative and myeloablative conditioning regimens in our institution. As busulfan has certain side effects and requires meticulous follow‐up during HSCT, we wished to convey our experience with a similar patient group who were administered treosulfan. Our aim was to describe challenges and outcomes which occurred while using both drugs for conditioning and finally to deliver the message that treosulfan is as safe and effective as busulfan. [ABSTRACT FROM AUTHOR]

Summary: Killer immunoglobulin‐like receptor (KIR) and KIR‐ligand (KIRL) interactions play an important role in natural killer cell‐mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR–KIRL interactions may identify donors with optimal NK cell‐mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR‐KIRL combinations and maximal inhibitory KIR ligand (IM‐KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR‐KIRL combinations were significantly predictive for reduced grade 3–4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM‐KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse‐free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

Summary: Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft‐versus‐host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA‐C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA‐A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA‐C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA‐DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA‐B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA‐DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA‐A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA‐C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA‐mediated cellular interactions and their role in the development of GVHD and relapse. [ABSTRACT FROM AUTHOR]

Belumosudil is a selective rho‐associated coiled‐coil‐containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft‐versus‐host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft‐versus‐host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension. Addition of sweetener and/or flavor vehicle improved the taste. Relative bioavailability of 200‐mg doses of the oral suspension and tablet in the fed state was similar for belumosudil and its metabolites (KD025m1 and KD025m2), but absorption was faster with the oral suspension (median time to maximum concentration: 2 vs 3 hours). Administration of the oral suspension with food increased exposure compared with fasted administration, with maximum observed concentration being increased by 16% and area under the concentration‐time curve from time 0 to the last measurable concentration (AUC0‐last) by 19%. Safety and tolerability were consistent with the known safety profile of belumosudil. These results may support administration of a 200‐mg belumosudil oral suspension with or without food. [ABSTRACT FROM AUTHOR]

Introduction: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. Objectives: This report describes the dental status of a cohort of patients within the Chronic Graft‐versus‐Host Disease Consortium and treatment rendered prior to transplant. Methods: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana‐Farber: n = 241). Both centers have institutional‐based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. Results: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). Conclusions: Retrospective analysis of pre‐AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care. [ABSTRACT FROM AUTHOR]

Objectives: Improved survival after hematopoietic cell transplantation (HCT) and an increasingly comorbid transplant population may give rise to new trends in the causes of death. Methods: This study includes all adult allogeneic HCT recipients transplanted at Rigshospitalet between January 1, 2010 and December 31, 2019. Underlying causes of death were determined using the Classification of Death Causes after Transplantation (CLASS) method. Results: Among 802 HCT recipients, 289 died during the study period. The main causes of death were relapse (N = 133, 46.0%), graft‐versus‐host disease (GvHD) (N = 64, 22.1%) and infections (N = 35, 12.1%). Multivariable analyses showed that with increasing transplant calendar year, a decreased risk of all‐cause mortality (HR 0.92, 95% CI 0.87–0.97) and death from GvHD (HR 0.87, 95% CI 0.78–0.97) was identified, but not for other specific causes. Standardized mortality ratios (SMRs) for all‐cause mortality decreased from 23.8 (95% CI 19.1–28.5) to 18.4 (95% CI 15.0–21.9) for patients transplanted in 2010–2014 versus 2015–2019, while SMR for patients who died from GvHD decreased from 8.19 (95% CI 5.43–10.94) to 3.65 (95% CI 2.13–5.18). Conclusions: As risk of all‐cause mortality and death from GvHD decreases, death from relapse remains the greatest obstacle in further improvement of survival after HCT. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the outcomes of patients with mantle cell lymphoma (MCL) who received different treatments. The study found that the overall survival rates at two and four years were 91% and 68% respectively. Patients who received rituximab maintenance therapy had higher survival rates compared to those who did not. The blastoid variant of MCL was associated with lower survival rates. The study also found that autologous hematopoietic stem cell transplant (HSCT) in an outpatient setting was safe and effective. Overall, the study suggests that the best available care, including rituximab maintenance therapy and HSCT, should be provided for MCL patients. [Extracted from the article]

Summary: Cytomegalovirus (CMV) DNAemia and disease are common complications in patients undergoing allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Few studies have compared the efficacy and safety of the HSCT donor and third‐party CMV‐specific cytotoxic T lymphocytes (CMV‐CTLs) in the treatment of CMV DNAemia and disease. In this study, we retrospectively compared the efficacy and safety of HSCT donor and third‐party CMV‐CTLs in patients with refractory CMV DNAemia or disease after allo‐HSCT at our centre from January 2017 to September 2021. Fifty‐three patients who received CMV‐CTL therapy were enrolled, including 40 in the donor group and 13 in the third‐party group, and they were adults aged 18 years or older. Within 6 weeks of treatment, 26 (65.0%) and 9 (69.2%) patients achieved complete response in the donor and third‐party groups (p = 1.000). The 2‐year overall survival was 59.6% (95% CI 46.1%–77.1%) and 53.8% (32.6%–89.1%) in the donor and third‐party groups (p = 0.860). Four (10.0%) patients in the donor group and two (15.4%) patients in the third‐party group developed acute graft‐versus‐host disease within 3 months after CMV‐CTL infusions. In conclusion, our data suggest that donor and third‐party CMV‐CTLs have comparable efficacy and safety for refractory CMV DNAemia and disease. [ABSTRACT FROM AUTHOR]

Background: The number of CD34+ cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34+ in bone marrow transplantation (BMT) remained unclear. Methods: We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021. Results: The median nucleated cell count (NCC) and CD34+ cell dose were 2.17 × 108/kg (range.56‐8.52) and 1.75 × 106/kg (.21–5.84), respectively. Compared with 104 patients in the low CD34+ group (below the median), 103 patients in the high CD34+ group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p =.001), reticulocyte (51.5% vs. 79.6%; p <.001), and platelet (39.4% vs. 72.8%; p <.001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft‐versus‐host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft‐versus‐host disease, either. While a positive correlation was observed between NCC and the CD34+ cell dose, a high CD34+ cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median. Conclusion: Measurement of CD34+ cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long‐term outcome in BMT. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the oral health status among allogeneic transplant recipients who were seen in a multidisciplinary graft‐versus‐host disease paediatric clinic at the University of California, San Francisco (UCSF). Methods: This was a retrospective cohort study of patients who underwent allogeneic transplants and were seen in the graft‐versus‐host disease paediatric clinic between January 2010 and September 2021. Demographic, medical and oral health data were recorded and analysed using descriptive statistics. Results: A total of 25 patients were seen in the paediatric graft‐versus‐host disease clinic (68% males) with a median age of 12 years at the time of transplant were included. Among them, 12 patients (48%) were diagnosed with oral chronic GVHD, 11 (44%) with dry mouth, four (16%) with oral pseudomembranous candidiasis, one (4%) with recrudescent Herpes Simplex Virus (HSV) infection and one (4%) with mammalian target of rapamycin‐inhibitor stomatitis and were managed by the oral medicine team, accordingly with medications, such as topical steroids (44%) and anti‐fungal (20%). Conclusions: HSCT recipients may present with a variety of oral complications. Patients may benefit by a multi‐disciplinary approach including a dental specialist as part of the cancer care team. [ABSTRACT FROM AUTHOR]

Hemorrhagic cystitis (HC) is a highly impacting complication in allogeneic hematopoietic stem cell transplantation (HSCT), occurring in 12%–37% of patients. The impact of transplant‐ and patient‐specific variables has been described, with a possible role for JCV and BKV, which may be cooperating with cytomegalovirus (CMV). Here, we analyze 134 letermovir‐exposed, CMV‐free patients, treated with the same cyclophosphamide‐based graft‐versus‐host disease (GVHD) prophylaxis, describing risk factors for HC. The overall incidence of HC was 23%. Patients with HLA mismatched transplant, higher comorbidity score, and receiving three alkylating agents with TBF (thiotepa, busulfan, and fludarabine) conditioning regimen had a higher risk of HC in multivariate analysis (OR: 4.48, 6.32, and 1.32, respectively). A HC‐score including male gender, TBF conditioning, and HLA‐mismatch stratifies the risk of HC in the first 100 days after HSCT. The role of BKV and JCV was not highly impacting in those patients, suggesting a possible synergistic effect between CMV and JCV in causing HC. HC can be interpreted as the combination of patient‐related factors, chemotherapy‐related toxicities—especially due to alkylating agents—and immunological elements. [ABSTRACT FROM AUTHOR]

The patient–donor human leukocyte antigen (HLA) match remains the most important prognostic factor for successful unrelated donor haematopoietic stem cell transplantation (UD‐HSCT). This single‐centre study comprised 125 adult patients with malignant haematological diseases undergoing their first UD‐HSCT. The primary goal of this study was to validate the impact of HLA matching on HSCT outcomes, specifically at the HLA‐DPB1 and HLA‐DRB3/4/5 loci. A multivariable Cox regression analysis with a backward selection algorithm was employed to assess the associations of selected prognostic factors with outcomes after UD‐HSCT. Any HLA locus mismatch was found to be associated with an increased incidence of grade II–IV acute graft versus host disease (aGvHD) at 100 days (p =.031; hazard ratio [HR] 1.935) and 6 months (p =.004; HR 2.284) after HSCT. The results of the following analyses also confirmed the strong impact of HLA‐DPB1‐only mismatch on the incidence of grade II–IV aGvHD at 100‐day (p =.006; HR 2.642) as well as at 6‐month (p =.007; HR 2.401) time periods. The HLA‐DPB1‐only mismatch was also shown to be statistically significantly associated with lower relapse incidence (p =.034; HR 0.333). The impact of the HLA‐DRB3/4/5 mismatch on outcomes was inconclusive, though the two and more HLA‐DPB1 + DRB3/4/5‐only mismatches showed a trend towards worse outcomes than a single mismatch. Based on our findings and those of more comprehensive studies, the extended HLA loci typing of patients and donors is suggested to avoid unexpected HLA mismatches during the UD selection. [ABSTRACT FROM AUTHOR]

Summary: Chimeric antigen receptor T‐cell (CAR‐T) therapy and bispecific T‐cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR‐T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo‐HCT). Thirty‐three MM patients with prior allo‐HCT received CAR‐T (n = 24) or BsAb (n = 9) therapy. CAR‐T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative. BsAb therapy resulted in an ORR of 44% (44% ≥ CR) and 44% MRD negative. Safety analysis showed grade ≥3 AEs in 92% of CAR‐T and 56% of BsAb patients. Cytokine release syndrome (CRS) occurred in 83% of CAR‐T and 78% of BsAb recipients, while immune effector cell‐associated neurotoxicity syndrome (ICANS) was observed in three CAR‐T patients. Infections of grade ≥3 were reported in 50% of CAR‐T and 44% of BsAb recipients. No exacerbation of graft‐versus‐host disease occurred except in one BsAb recipient. CAR‐T and BsAb therapies appear to be feasible, safe and provide deep and durable responses in MM patients with prior allo‐HCT. [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]

Graft‐versus‐host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments. [ABSTRACT FROM AUTHOR]

Introduction: Pneumocystis jirovecii pneumonia (PJP) is a rare complication of hematopoietic stem cell transplantation (HSCT). Primary prophylaxis for 6–12 months post‐HSCT is the standard approach. However, there is no consensus regarding the optimal duration of prophylaxis. Methods: We identified patients who developed PJP more than 1‐year post‐HSCT. All patients had previously received 12 months of PJP prophylaxis. PJP was diagnosed based on clinical findings and the detection of P. jirovecii in bronchoalveolar lavage (BAL) using polymerase chain reaction (PCR). The CD4+ T‐cell percentage was determined using flow cytometry. Data expressed as median (interquartile range). Results: Ten patients developed PJP at 17.5 months (16–24 months) post‐HSCT. PJP diagnosis occurred 5.5 months (3–15 months) after discontinuing prophylaxis. Eight patients received anti‐thymocyte globulin (ATG) as graft versus host disease (GVHD) prophylaxis. At diagnosis, only one patient had lymphopenia; all patients had CD4+ T‐lymphocyte counts ≥0.2 × 109/L (median 0.337 × 109/L). Three patients had concomitant bacterial infections. The clinical presentation was mild; only three required hospitalization, none of them required intensive care and there were no deaths. Conclusion: There is a need to develop risk‐adapted prophylactic strategies in the contemporary era using ATG‐based GVHD prophylaxis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Transfusion of cold‐stored whole blood is the preferred resuscitation method for trauma patients but may cause transfusion‐associated graft‐versus‐host disease (TA‐GVHD). Standard clinical practice to prevent this is to irradiate blood components with gamma‐rays. X‐ray irradiations are also a safe and effective alternative to gamma‐ray irradiation. We established a visual mouse model of TA‐GVHD to compare the viability and function of lymphocytes exposed to gamma‐ and x‐ray irradiation. Materials and Methods: A haploidentical transplantation mouse model was established to simulate TA‐GVHD with Balb/c mice as donors and hybrid F1 CB6 mice (Balb/c × C57) as recipients. Spleen cells from Tg‐Fluc+ Balb/c mice were isolated and irradiated with gamma‐rays and x‐rays. Lymphocyte activation, apoptosis and proliferation post phorbol 1 2‐myristate 1 3‐acetate (PMA) stimulation were evaluated. After transfusion, we monitored Fluc+ lymphocytes daily by bioluminescence imaging. Recipients were euthanized on day 21, and tissues were examined pathologically and for inflammatory cytokines. Results: The viability of gamma‐ or x‐ray irradiated lymphocytes decreased significantly with slight changes in proliferation in vivo after transfusion. Compared with the non‐irradiated group, both the gamma‐ and x‐ray irradiated groups showed significantly decreased clinical scoring and inflammatory cytokine levels. The fluorescence intensity of the body and target organs was reduced after irradiation. Conclusion: No recipients acquired TA‐GVHD after lymphocyte transfusion subjected to gamma‐ or x‐rays, showing that x‐rays inactivate as well as gamma rays and are suitable for irradiating whole blood. [ABSTRACT FROM AUTHOR]

Quantification of Torque teno virus (TTV) load emerged as a marker of immunosuppression. Associations of TTV load with complications and survival after allogeneic hematopoietic cell transplantation (allo‐HCT) were controversial in published studies. In this prospective study, we aimed to identify factors influencing TTV load after allo‐HCT and to determine whether the TTV load is associated with complications or outcomes. Seventy allo‐HCT recipients were included. TTV DNA load was quantified in 469 plasma samples of 70 patients from Day (D) 15 before D120 after transplantation. The influence of transplant characteristics on TTV load and the associations of TTV load with viral infections, acute graft versus host disease, mortality, and relapse were analyzed. More than 80% of patients were TTV DNA positive from D30 after transplantation onwards. Median TTV load increased between D30 and D60 post‐transplantation. Patients with lymphoid malignancies had higher TTV load than those with myeloid malignancies. Myeloablative conditioning was associated with higher TTV loads. Patients with no measurable residual disease at transplant had higher TTV loads. High TTV load at D90 post‐transplantation was associated with lower overall survival and at D120 post‐transplantation was associated with higher relapse rate. In conclusion, TTV load at time points later than D90 after allo‐HCT may be useful to assess prognosis. [ABSTRACT FROM AUTHOR]

This article discusses a case of chronic cutaneous graft-versus-host disease (GVHD) occurring exclusively on striae distensae. GVHD is a complication that can occur after allogeneic hematopoietic cell transplantation, and it primarily affects the liver, gastrointestinal tract, and skin. The patient in this case study was a 16-year-old male who developed skin lesions on his striae distensae after undergoing transplantation for B-cell acute lymphoblastic leukemia. The lesions were characterized by erythematous papules and plaques, and the patient also experienced hepatic and gastrointestinal symptoms. Treatment with corticosteroids and other medications provided some relief, but the patient's condition did not fully improve. The article highlights the rarity of this manifestation of chronic GVHD and emphasizes the importance of recognizing atypical presentations of the disease. [Extracted from the article]

We present two pediatric patients who exhibited an unusual clinical presentation of cutaneous acute graft‐versus‐host disease (GVHD), characterized by livedo‐like appearance. Such manifestations of cutaneous acute GVHD have not been previously documented. [ABSTRACT FROM AUTHOR]

Summary: Data from 200 children with high‐risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) between 2015 and 2021 at our institution were analysed. The 4‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100‐day cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (aGVHD) were 41.1% and 9.5% respectively. The 4‐year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate‐to‐severe cGVHD was 27.3%. Minimal residual disease (MRD)‐positive (MRD+) status pre‐HSCT was significantly associated with lower survival and a higher risk of relapse. The 4‐year OS, EFS and CIR differed significantly between patients with MRD+ pre‐HSCT (n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD‐negative (MRD‐) pre‐HSCT (n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non‐DS‐AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430–6.763), 3.145 (1.628–6.074) and 3.250 (1.529–6.910) respectively; p‐values were 0.004, 0.001 and 0.002 respectively). Thus, haplo‐HSCT can be a therapy option for these patients, and MRD status pre‐HSCT significantly affects the outcomes. As patients with non‐DS‐AMKL have extremely poor outcomes, even with haplo‐HSCT, a combination of novel therapies is urgently needed. [ABSTRACT FROM AUTHOR]