Allogeneic Hematopoietic Stem Cell Transplantation Research Articles

Allogeneic stem cell transplantation in de novo core-binding factor acute myeloid leukemia in first complete remission: data from the EBMT.

Core-binding factor acute myeloid leukemia (CBF-AML) represents 12-15% of all AML cases. Although CBF positivity infers a survival advantage, overall survival (OS) remains dismal. Treatment is with cytarabine/anthracycline-based chemotherapy induction followed by high-dose cytarabine (HiDAC) consolidation. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is reserved for relapse or for patients having not achieved MRD-negativity at high risk for relapse. The role of SCT in first complete remission (CR1) remains controversial and is considered in high risk conditions. In this retrospective, multi-national, European Society for Blood and Marrow Transplantation (EBMT)-based study, we identified 1901 patients with de novo CBF-AML who received an allo-SCT or autologous transplantation (ASCT) in CR1. 65.5% harbored t(8;21) and 34.4% inv(16). In this group, the majority (77%) were treated with allo-SCT in CR1. In multivariate analysis, treatment with allo-SCT was an independent and significant, negative predictor of NRM and OS (HR 4.26, p < 0.0001 and HR 1.67, p = 0.003) and among patients treated with allo-SCT, those treated with MSD had the best outcomes, comparable to those treated with ASCT.There was no interaction between the type of transplant and MRD status at time of SCT. In both, MRD-negative and MRD-positive groups, NRM was worse in the allo-SCT group (MRD-: 12.9% vs 5.2%, p = 0.007; MRD+: 10.6% vs 0%, p = 0.004). We therefore demonstrated that consolidation in CR1 with allo-SCT results in worse outcomes than ASCT. Whether consolidation with ASCT yields better outcomes than chemotherapy alone or chemotherapy in combination with Gemtuzumab Ozogamicin is yet to be investigated.

Clinical outcomes of allogeneic hematopoietic stem cell transplantation from matched sibling donor for myelofibrosis

Objective: To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF). Methods: In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People's Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed. Results: Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [M (Q1, Q3)] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion: Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia.

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

A-232 Outcome of cutaneous T-cell lymphomas after allogeneic hematopoietic stem cell transplantation : focus on relapses and their management

A-232 Outcome of cutaneous T-cell lymphomas after allogeneic hematopoietic stem cell transplantation : focus on relapses and their management

The Effects of Two Kinds of Gargles on Oral Mucositis in Patients After Allogeneic Stem Cell Transplantation

ObjectiveTo compare the effects of two kinds of gargles (Koushu & Koutai) on oral mucositis (OM) in patients with agranulocytosis. MethodsOne hundred and eighty patients who underwent allogeneic hematopoietic stem cell transplantation in the Peking University Institute of Hematology were enrolled from March 2018 to January 2019. The subjects were randomly divided into two groups by random number table. The observation group was gargled with Koushu, while the control group was gargled with Koutai Patients in both groups used 10-15 ml of gargles for 2 minutes when awake in the morning, 30 minutes after each meal and before sleep. The two groups used the same way to gargle except the types of gargle. The difference of incidence, grade, healing time and pain grade of oral mucositis were analyzed. ResultsThe incidence of oral mucositis in the observation group was significantly lower than that in the control group (P<0.01).There were no significant difference in grade of oral mucositis, healing time or pain grade between the two groups (P>0.05). The effect of the Koushu on the prevention of OM among the patients with agranulocytosis is better than that of the Koutai. Koushu is better suited than Koutai as a prevention and treatment option for the patients.

Gastric Bleeding in Stem Cell Transplantation: A Focus on Gastric Vascular Ectasia Under Post-Transplant Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil Prophylaxis

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023. Data were collected on transplant procedures, complications, and GIB incidents, with UGIB cases undergoing endoscopic and histologic examination. Out of 559 patients, 38 (6.6%) experienced UGIB, with 27 cases (70%) attributed to GVE. GVE typically presented as melena or hematemesis at a median time of 68 days (range, 29-125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-month cumulative incidence of GVE was 5.1%. Older age (≥60 years) and diagnosis of myelodysplastic/myeloproliferative neoplasm were significant risk factors. All cases resolved with no attributable mortality with supportive measures including transfusions, proton-pump inhibitors, and sirolimus withdrawal in some cases. GVE is a notable cause of UGIB in HSCT recipients on PTCY-based GVHD prophylaxis, presenting significant morbidity but favorable outcomes with appropriate management. The potential role of sirolimus and conditioning agents in GVE pathogenesis warrants further investigation.

Efficacy and safety of hetrombopag in the treatment of recombinant human thrombopoietin–resistant thrombocytopenia after allogeneic hematopoietic stem cell transplantation

BackgroundThrombocytopenia after allogeneic hematopoietic cell transplantation is a challenging clinical problem. Recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists are increasingly used in posttransplant thrombocytopenia. However, the use of hetrombopag in patients with posttransplant thrombocytopenia, especially in patients with resistance to rhTPO, has not yet been reported. ObjectivesThe present study aimed to investigate the efficacy and safety of hetrombopag in patients with rhTPO-resistant posttransplant thrombocytopenia. MethodsThis retrospective study included 21 patients with rhTPO-resistant posttransplant thrombocytopenia who received hetrombopag from August 2021 to July 2022. The primary endpoint was the overall response rate, including partial response and complete response (CR). We also evaluated the predictors of hetrombopag efficacy and adverse events. ResultsThe overall response rate to hetrombopag was 81%, and the CR rate was 62%. The median time from hetrombopag initiation to response and CR were 16 and 31 days, respectively. Decreased megakaryocytes in bone marrow negatively correlated with CR to hetrombopag (P = .027). All the patients tolerated hetrombopag well without any significant increase in adverse events. At the last follow-up, 71% of responders had discontinued hetrombopag and sustained their best response. ConclusionOur results suggested that hetrombopag is an effective treatment option to promote platelet recovery in patients with posttransplant thrombocytopenia, even in patients resistant to rhTPO.

Clinical and Radiological Characteristics of Classical and Variant Type of Posterior Reversible Encephalopathy Syndrome on Prognosis Following Hematopoietic Stem Cell Transplantation in Pediatric Patients: A Single-Center Experience.

Hematopoietic stem cell transplant is increasingly being used as a curative therapeutic option for patients with hematologic malignancies and nonmalignant diseases. Here, we aimed to determine the frequency and features of typical and atypical central variants of posterior reversible encephalopathy syndrome in children who had undergone an allogeneic hematopoietic stem cell transplant procedure for any indication at a single center. We retrospectively analyzed 101 pediatric patients between aged 6 months and 18 years who had undergone hematopoietic stem cell transplant for any indication between 2010 and 2023. We evaluated morbidity and mortality rates and several risk factors, therapies, and outcomes associated with posterior reversible encephalopathy syndrome. Medical data were obtained from patients' electronic health records. In 101 patients who underwent hematopoietic stem cell transplant, the most common diagnosis was acute lymphoblastic leukemia (n = 46; 45.5%). Median time to onset of posterior reversible encephalopathy syndrome was 20 days (range, 10-108 days) posttransplant. Most cases of posterior reversible encephalopathy syndrome were typical, and 16 patients (15.8%) had the central variant. Headache was the most common clinical manifestation (79.2%). Rates of steroid use and complete remission in patients with the central variant were significantly (P < .05) lower than in the group with the typical variant. Mortality rates were significantly higher in patients with the central variant (n = 10, 62.5%) compared with those with the typical variant (n = 5, 5.9%) (P < .001). Patients with the central variant of posterior reversible encephalopathy syndrome showed significantly increased risk of mortality. Because this clinical-radiological condition frequently manifests with atypical findings on magnetic resonance imaging, consideration of posterior rever-sible encephalopathy syndrome as a potential diagnosis is crucial when the clinical presentation is consistent but radiological findings are not typical to posterior reversible encephalopathy syndrome.

Female-to-male allogeneic transplantation affects outcomes differently according to the type of haplo-transplantation

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49–0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68–1.16], P = 0.40; NRM 0.98 [95% CI: 0.68–1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.

Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT

The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.

Risk factors and long-term outcomes for human herpesvirus 6 encephalitis in the early period after allogeneic stem cell transplantation.

Human herpesvirus 6 (HHV6) encephalitis is a rare but life-threatening complication for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, reports on susceptibility factors and clinical outcomes are limited. We enrolled HHV6 encephalitis patients following allo-HSCT between 2018 and 2022, then conducted a 1:4 nested case-control cohort study to evaluate risk factors and long-term outcomes. Among 1350 patients, 20 (1.48%) developed HHV6 encephalitis, with a median onset time of 25.5 days after HSCT. Patient age<30 (odds ratio [OR], 3.24, P = 0.016) and NK cell count<115/ul at 21 days (OR, 6.07, P = 0.018) were identified as independent risk factors in multivariate analysis. Moreover, the HHV6 encephalitis group was significantly associated with higher incidence of grade II-IV graft-versus-host disease (aGVHD) (hazard ratio [HR], 5.52, P < 0.001) and transplant-associated microangiopathy (HR,9.86, P < 0.001), and demonstrated a significantly higher non-relapse mortality (NRM) (HR, 5.28, P = 0.004) and a lower overall survival (HR, 4.34, P = 0.001) or progression-free survival (HR, 3.94, P = 0.001) compared to control group. In conclusion, patients <30 years old or with delayed NK cell recovery are more susceptible to HHV6 encephalitis after allo-HSCT, and patients with HHV6 encephalitis after transplantation have poorer clinical outcomes.

Healthcare Resource Utilization and Associated Costs in Patients With Chronic Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation in England

Limited evidence suggests chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases healthcare resource utilization (HCRU) and costs. However, this burden has not been well characterized in England. This study assesses secondary care HCRU and costs for patients following allo HSCT in England with cGvHD and patients who did not develop graft-versus-host disease (GvHD). Further stratification was performed among patients who did or did not subsequently receive high-cost therapies for the treatment of cGvHD. This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017 to March 2022. HES data captures information on reimbursed diagnoses and procedures from all National Health Service (NHS) secondary care admissions and attendances in England. High-cost drugs as defined by NHS England are recorded in HES, these drugs and other procedures including plasma exchange, were used to identify patients with cGvHD who were in receipt of high-cost therapies. HCRU and costs were described for patients with cGvHD following allo-HSCT (n = 721) and were matched with patients with no evidence of GvHD following allo-HSCT (n = 718). HCRU and costs were also described for the subset of patients with cGvHD (n = 198) following receipt of high-cost therapies and patients with cGvHD prior to or without such therapies (n = 523). A higher proportion of patients with cGvHD had at least one inpatient or intensive care unit (ICU) admission or emergency care attendance than patients without GvHD (inpatient: 74.6% versus 66.6%; emergency care: 39.3% versus 30.5%; ICU: 7.4% versus 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% versus 84.1%; respectively). The cost across all secondary care settings was higher for patients with cGvHD than patients without GvHD, with a mean cost of inpatient admissions of £17,339 ppy for those with cGvHD versus £8548 ppy in patients without GvHD. A higher proportion of patients who received high-cost therapies for the treatment of cGvHD had at least one secondary care admission or attendance, than patients who did not (inpatient: 85.4% versus 66.4%; ICU: 7.1% versus 5.4%; outpatient: 87.9% versus 76.7%; emergency care: 44.4% versus 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 versus 8.2 ppy, respectively) for all-cause inpatient admissions after treatment than patients who did not. In all secondary care settings, the total cost ppy was higher for patients who received high-cost therapies for the treatment of cGvHD, than for those who did not. Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean cost (£21,137 versus £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. This study demonstrates that cGvHD and the use of associated high-cost therapies impacts healthcare activity and costs across various secondary care settings in England more than patients without GvHD and patients with cGvHD who received no high-cost therapies.

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Impact of Serum Albumin &amp; Pre-albumin as well as Anthropometric Measurements on Long Term Survival Outcomes after Allogeneic Stem Cell Transplantation

Abstract Background Allogeneic HSCT is the treatment of choice for treatment of patients with high risk features of acute leukemia or those who are relapsed after standard treatment. By now, there are few studies on nutritional assessment of hematological patients before and after HSCT, and additionally, most rely on one single assessment method. Objective Evaluating nutritional indicators as well as anthropometric measurements in long term survivors post-transplant, identifying their relationship on transplant outcomes. Methods The present work included 30 patients with two or more years after allogeneic stem cell transplantation who were following up at Bone Marrow Transplantation Unit, Ain Shams University Hospitals, during the Jan-2019 till Jan- 2023. We assessed nutritional lab parameters including albumin, prealbumin as well as anthropometric measurements including BMI, waist, circumference, waist hip ratio and body fat percentage using bioelectric impendence in long term survivors as well as assessment of quality of life using FACT-BMT questionnaire. Results We found statistically significant association between nutritional lab parameters as well as anthropometric measurements with late transplant outcome including incidence of chronic GVHD, disease relapse and transplant related mortality as well as post-transplant quality of life. Conclusion Nutritional lab biomarkers and anthropometric measurements in long term survivors post-allogeneic stem cell transplantation were a low cost, non- invasive biomarkers for early and late transplant complications, patients’ survival and quality of life.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.

Insights into cytomegalovirus-associated T cell receptors in recipients following allogeneic hematopoietic stem cell transplantation

BackgroundCytomegalovirus (CMV) reactivation is a serious problem in recipients of allogeneic hematopoietic stem cell transplantation. Long-term latency depends on specific T cell immune reconstitution, which identifies various pathogens by T cell receptors (TCRs). However, the mechanisms underlying the selection of CMV-specific TCRs in recipients after transplantation remain unclear.MethodsUsing high-throughput sequencing and bioinformatics analysis, the T cell immune repertoire of seven CMV reactivated recipients (CRRs) were analyzed and compared to those of seven CMV non-activated recipients (CNRs) at an early stage after transplant.ResultsThe counts of unique complementarity-determining region 3 (CDR3) were significantly higher in CNRs than in CRRs. The CDR3 clones in the CNRs exhibit higher homogeneity compared to the CRRs. With regard to T cell receptor β-chain variable region (TRBV) and joint region (TRBJ) genotypes, significant differences were observed in the frequencies of TRBV6, BV23, and BV7–8 between the two groups. In addition to TRBV29–1/BJ1–2, TRBV2/BJ2–2, and TRBV12–4/BJ1–5, 11 V-J combinations had significantly different expression levels between CRRs and CNRs.ConclusionsThe differences in TCR diversity, TRBV segments, and TRBV-BJ combinations observed between CNRs and CRRs might be associated with post-transplant CMV reactivation and could serve as a foundation for further research.

Which allogeneic hematopoietic cell transplant recipients have an increased risk for delayed-onset clinically significant cytomegalovirus infection after letermovir prophylaxis?

Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT. Retrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event. Among 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty-six (15.7%) developed a breakthrough csCMVi. Delayed-onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed-onset csCMVi (OR 0.23). Having a matched unrelated donor, a CMV donor negative/recipient positive status, and a non-AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients.

Association between positive affect, flourishing, quality of life, and psychological distress in allogeneic hematopoietic stem cell transplantation

Purpose To examine the associations between state positive psychological well-being (PPWB) constructs, mood, and quality of life (QOL) in hematopoietic stem cell transplantation (HSCT) survivors. Design The study was a secondary analysis of cross-sectional data. Sample/Methods We analyzed self-report data assessing positive affect, flourishing, QOL, depression and anxiety, and PTSD symptoms from 158 allogeneic HSCT recipients at day-100 post-transplant enrolled in supportive care studies. Findings Univariate analysis showed that factors associated with greater levels of various state PPWB constructs include older age, disability status, greater social support, and presence of graft-versus-host disease. Multivariate analysis showed that state PPWB constructs—greater levels of positive affect and flourishing—were significantly associated with better QOL and lower PTSD, anxiety, and depression symptomatology. Implications Our findings suggest that longitudinal studies are needed to examine the links between state PPWB constructs and HSCT outcomes, which may inform population specific interventions and opportunities to improve outcomes.

Letermovir at a Prophylactic Dose for Cytomegalovirus Infection in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Study in Japan.

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.