Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease.

Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD, and explores relevant research progress in prevention and treatment research.

Research advances on short-chain fatty acids in gastrointestinal acute graft-versus-host disease Gastrointestinal acute graft-versus-host disease (GI-aGVHD) is a severe early complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been shown that the intestinal microbiota plays a critical role in this process. As metabolites of the intestinal microbiota, short-chain fatty acids (SCFAs) are vital for maintaining the host-microbiota symbiotic equilibrium. This article provides an overview of the protective effect of SCFAs in the gastrointestinal tract, emphasizes their association with GI-aGVHD and explores relevant research progress in prevention and treatment research.

High dose total marrow irradiation (TMI) does not increase long-term toxicity of myeloablative fludarabine/busulfan (FluBu4) conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT).

OBJECTIVES: Based on a previous phase 1 study, total marrow irradiation (TMI) at 9Gy was added to a myeloablative FluBu4 conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies. Here, we report on the long-term toxicity of TMI combined with FluBu4 and compare it to patients who received only FluBu4. METHODS: We retrospectively analyzed 38 consecutive patients conditioned with FluBu4/TMI (n = 15) or FluBu4 (n = 23, control group) who had at least 1 year follow-up post-transplant. The rate of long-term adverse events that have been previously associated with total body irradiation (TBI) was analyzed in the two groups. RESULTS: The baseline characteristics did not differ between the two groups. The control group had a longer median follow-up (71.2 mo) than the TMI group (38.5 mo) (p = .004). The most common adverse events were xerostomia, dental complications, cataracts, or osteopenia and did not differ between the two groups. Cognitive dysfunction or noninfectious pneumonitis, often detected after high dose TBI, were also not different in the two groups (p = .12 and p = .7, respectively). There was no grade 4 adverse event. CONCLUSION: Our results suggest that a conditioning regimen with TMI 9Gy and FluBu4 does not increase long-term adverse events after allogeneic HSCT.

[Successful bridging therapy with alectinib prior to allogeneic stem cell transplantation for refractory ALK-positive anaplastic large cell lymphoma].

Although alectinib is effective for relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL) and has a favorable safety profile, its role as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the role of allo-HSCT itself in this setting are unknown. A 35-year-old man with ALK-positive ALCL experienced relapse after first-line therapy with CHOP. Brentuximab vedotin led to partial response and high-dose chemotherapy combined with autologous HSCT was performed. However, disease progressed 15 months after transplantation, and alectinib was initiated. Complete response (CR) was achieved after three months of treatment, and alectinib was continued for 5 months. After cessation of alectinib, allogeneic bone marrow transplantation from an HLA 1-locus mismatched unrelated donor was performed after conditioning with fludarabine, busulfan, and total body irradiation. GVHD prophylaxis consisted of tacrolimus and short-term methotrexate. The post-transplant course was unremarkable except for grade I acute GVHD. The lymphoma has not recurred for 2 years after allo-HSCT without resuming alectinib. The clinical course of our case suggests that alectinib bridging therapy and allo-HSCT are effective in relapsed/refractory ALK-positive ALCL.

Predicting delayed extubation and transfer to the intensive care unit in children undergoing posterior fusion surgery for scoliosis : A retrospective observational study.

BACKGROUND: Delayed extubation and transfer to the intensive care unit (ICU) in children undergoing major scoliosis surgery may increase postoperative complications, prolong hospital stay, and increase medical expenses; however, whether a child will require delayed extubation or transfer to the ICU after scoliosis orthopedic surgery is not fully understood. In this study, we reviewed the risk factors for delayed extubation and transfer to the ICU after scoliosis orthopedic surgery in children. METHOD: The electronic medical records of pediatric patients (≤ 18 years) who underwent posterior spinal fusion surgery between January 2018 and November 2021 were reviewed and analyzed. Patient characteristics (age, sex, body mass index, American Society of Anesthesiologists, ASA, grade, preoperative lung function, and congenital heart disease), preoperative Cobb angle, scoliosis type, correction rate, vertebral fusion segments, pedicle screws, surgical osteotomy, intraoperative bleeding, intraoperative allogeneic transfusion, intraoperative hemoglobin changes, intraoperative mean arterial pressure changes, intraoperative tidal volume (ml/kg predicted body weight), surgical time, postoperative extubation, and transfer to the ICU were collected. The primary outcomes were delayed extubation and transfer to the ICU. Multivariate logistic regression models were used to determine the risk factors for delayed extubation and ICU transfer. RESULTS: A total of 246 children who satisfied the inclusion criteria were enrolled in this study, of whom 23 (9.3%) had delayed extubation and 81 (32.9%) were transferred to the ICU after surgery. High ASA grade (odds ratio [OR] 5.42; 95% confidence interval [CI] 1.49-19.78; p = 0.010), high Cobb angle (OR 1.04; 95% CI 1.02-1.07; p < 0.001), moderate to severe pulmonary dysfunction (OR 10.9; 95% CI 2.00-59.08; p = 0.006) and prolonged surgical time (OR 1.01; 95% CI 1.00-1.03; p = 0.040) were risk factors for delayed extubation. A high Cobb angle (OR 1.02; 95% CI 1.01-1.04; p = 0.004), high intraoperative bleeding volume (OR 1.06; 95% CI 1.03-1.10; p = 0.001), allogeneic transfusion (OR 3.30; 95% CI 1.24-8.83; p = 0.017) and neuromuscular scoliosis (OR 5.38; 95% CI 1.59-18.25; p = 0.007) were risk factors for transfer to the ICU. A high Cobb angle was a risk factor for both delayed extubation and ICU transfer. Age, sex, body mass index, number of vertebral fusion segments, correction rate, and intraoperative tidal volume were not associated with delayed postoperative extubation and ICU transfer. CONCLUSION: The most common risk factor for delayed extubation and ICU transfer in pediatric patients who underwent posterior spinal fusion was a high Cobb angle. Determining risk factors for a poor prognosis may help optimize perioperative respiratory management strategies and planning of postoperative care for children undergoing complicated spinal surgery.

Mismatched related donor allogeneic haematopoietic cell transplantation compared to other donor types for Ph+ chronic myeloid leukaemia: A retrospective analysis from the Chronic Malignancies Working Party of the EBMT.

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.

The role of immune reconstitution in relapse after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Leukemia relapse following stem cell transplantation remains a significant barrier to long-term remission. Timely and balanced immune recovery after transplantation is crucial for preventing leukemia relapse. AREAS COVERED: After an extensive literature search of PubMed and Web of Science through October 2023, we provide an overview of the dynamics of immune reconstitution and its role in controlling leukemia relapse. We also discuss strategies to promote immune reconstitution and reduce disease recurrence following allogeneic hematopoietic stem cell transplantation. EXPERT OPINION: Immune reconstitution after transplantation has substantial potential to prevent relapse and might predict disease recurrence and prognosis. High dimensional cytometry, multi-omics, and T cell repertoire analysis allow for a more comprehensive and detailed understanding of the immune system's dynamics post-transplantation, and contribute to the identification of rare immune cell subsets or potential biomarkers associated with successful immune reconstitution or increased risk of complications. Strategies to enhance the immune system, such as adoptive immunotherapy and cytokine-based therapy, have great potential for reducing leukemia relapse after transplantation. Future research directions should focus on refining patient selection for these therapies, implementing appropriate and timely treatment, investigating combination approaches to maximize therapeutic outcomes, and achieving a robust graft-versus-leukemia (GVL) effect while minimizing graft-versus-host disease (GVHD) for optimal results.

Investigation of biomarkers to predict outcomes in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. OBJECTIVE: The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. STUDY DESIGN: A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. RESULTS: A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30-5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14-6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. CONCLUSION: The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further investigations are needed to validate the novel markers, analysis of the pathophysiology, and application to treatment settings other than HCT.

Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect.

Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft-versus-leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.

[The effect of glucose-6-phosphate dehydrogenase deficiency on allogeneic hematopoietic stem cell transplantation in patients with hematological disorders].

Objectives: To determine the effect of glucose-6-phosphate-dehydrogenase (G6PD) deficiency on patients' complications and prognosis following allogeneic stem cell hematopoietic transplantation (allo-HSCT) . Methods: 7 patients with G6PD deficiency (study group) who underwent allo-HSCT at Peking University People's Hospital from March 2015 to January 2021 were selected as the study group, and thirty-five patients who underwent allo-HSCT during the same period but did not have G6PD deficiency were randomly selected as the control group in a 1∶5 ratio. Gender, age, underlying diseases, and donors were balanced between the two groups. Collect clinical data from two patient groups and perform a retrospective nested case-control study. Results: The study group consisted of six male patients and one female patient, with a median age of 37 (range, 2-45) years old. The underlying hematologic diseases included acute myeloid leukemia (n=3), acute lymphocytic leukemia (n=2), and severe aplastic anemia (n=2). All 7 G6PD deficiency patients achieved engraftment of neutrophils within 28 days of allo-HSCT, while the engraftment rate of neutrophils was 94.5% in the control group. The median days of platelet engraftment were 21 (6-64) d and 14 (7-70) d (P=0.113). The incidence rates of secondary poor graft function in the study group and control group were 42.9% (3/7) and 8.6% (3/35), respectively (P=0.036). The CMV infection rates were 71.4% (5/7) and 31.4% (11/35), respectively (P=0.049). The incidence rates of hemorrhagic cystitis were 57.1% (4/7) and 8.6% (3/35), respectively (P=0.005), while the bacterial infection rates were 100% (7/7) and 77.1% (27/35), respectively (P=0.070). The infection rates of EBV were 14.3% (1/7) and 14.3% (5/35), respectively (P=1.000), while the incidence of fungal infection was 14.3% (1/7) and 25.7% (9/35), respectively (P=0.497). The rates of post-transplant lymphoproliferative disease (PTLD) were 0% and 5.7%, respectively (P=0.387) . Conclusions: The findings of this study indicate that blood disease patients with G6PD deficiency can tolerate conventional allo-HSCT pretreatment regimens, and granulocytes and platelets can be implanted successfully. However, after transplantation, patients should exercise caution to avoid viral infection, complications of hemorrhagic cystitis, and secondary poor graft function.

[Short-term substitution of calcineurin inhibitors (CNI) with recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed. Results: Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed. Conclusions: When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.

Combination of metagenomic next-generation sequencing and conventional tests unraveled pathogen profiles in infected patients undergoing allogeneic hematopoietic stem cell transplantation in Jilin Province of China.

Background: Infection is the main cause of death for patients after allogeneic hematopoietic stem cell transplantation (HSCT). However, pathogen profiles still have not been reported in detail due to their heterogeneity caused by geographic region. Objective: To evaluate the performance of metagenomic next-generation sequencing (mNGS) and summarize regional pathogen profiles of infected patients after HSCT. Methods: From February 2021 to August 2022, 64 patients, admitted to the Department of Hematology of The First Hospital of Jilin University for HSCT and diagnosed as suspected infections, were retrospectively enrolled. Results: A total of 38 patients were diagnosed as having infections, including bloodstream (n =17), pulmonary (n =16), central nervous system (CNS) (n =4), and chest (n =1) infections. Human betaherpesvirus 5 (CMV) was the most common pathogen in both bloodstream (n =10) and pulmonary (n =8) infections, while CNS (n =2) and chest (n =1) infections were mainly caused by Human gammaherpesvirus 4 (EBV). For bloodstream infection, Mycobacterium tuberculosis complex (n =3), Staphylococcus epidermidis (n =1), and Candida tropicalis (n =1) were also diagnosed as causative pathogens. Furthermore, mNGS combined with conventional tests can identify more causative pathogens with high sensitivity of 82.9% (95% CI 70.4-95.3%), and the total coincidence rate can reach up to 76.7% (95% CI 64.1-89.4%). Conclusions: Our findings emphasized the importance of mNGS in diagnosing, managing, and ruling out infections, and an era of more rapid, independent, and impartial diagnosis of infections after HSCT can be expected.

Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy.

Stem cells, renowned for their unique regenerative capabilities, present significant hope in treating stroke, a major cause of disability globally. This review offers a detailed analysis of stem cell applications in stroke (ischemic and hemorrhagic) recovery. It examines therapies based on autologous (patient-derived), allogeneic (donor-derived), and Granulocyte-Colony Stimulating Factor (G-CSF) based stem cells, focusing on cell types such as Mesenchymal Stem/Stromal Cells (MSCs), Bone Marrow Mononuclear Stem Cells (BMMSCs), and Neural Stem/Progenitor Cells (NSCs). The paper compiles clinical trial data to evaluate their effectiveness and safety and addresses the ethical concerns of these innovative treatments. By explaining the mechanisms of stem cell-induced neurological repair, this review underscores stem cells' potential in revolutionizing stroke rehabilitation and suggests avenues for future research.

Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for adolescent and adult Tlymphoblastic leukemia /lymphoma: a large cohort multicenter study in China.

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.

IMPROVE-BMT: A Pilot Randomized Controlled Trial of Prehabilitation Exercise for Adult Hematopoietic Stem Cell Transplant Recipients.

Background: There is limited evidence on the effects of aerobic and resistance training exercise interventions to improve physical function and patient-reported outcomes prior to autologous and allogeneic hematopoietic stem cell transplant (HSCT). IMPROVE-BMT was a single-site, pilot randomized controlled trial investigating the feasibility, acceptability, and safety of a pragmatic resistance training exercise program prior to HSCT compared to usual HSCT care. Secondary aims included differences in physical function between the exercise group (EX) and usual care control group (UC). Methods: Outcome measurements were assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT, and +100 days post-HSCT. The exercise intervention was a home-based exercise program that incorporated resistance-band and bodyweight exercises. Results: Acceptability among participants was 83%; exercise adherence averaged at 92%; and there were zero exercise-related adverse or serious adverse events. The average pre-transplant exercise phase was 6.28 weeks (2.71-18.29 weeks). EX (n = 36) demonstrated larger increases in the six-minute walk test distance, short physical performance battery scores, and 30-s chair stands compared to UC (n = 38) and demonstrated significant within-group improvements for the six-minute walk test, the short physical performance battery, the 30-s chair stands, and the timed up-and-go test. Conclusions: IMPROVE-BMT demonstrates that pragmatic exercise is highly feasible for HSCT recipients and can potentially lead to enhanced recovery that may not be achievable in non-exercisers.

Donor Lymphocyte Infusion in the Treatment of Post-Transplant Relapse of Acute Myeloid Leukemias and Myelodysplastic Syndromes Significantly Improves Overall Survival: A French-Italian Experience of 134 Patients.

BACKGROUND: Disease relapse after allogeneic stem cell transplantation (allo-SCT) is the main challenge for curing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We investigated the overall survival (OS) after allo-SCT relapse according to different therapeutic approaches. METHODS: We analyzed 134 patients who relapsed after allo-SCT performed between 2015 and 2021 at Saint-Antoine University Hospital, Paris and Spedali Civili di Brescia, Brescia. Of these, 103 (77%) were treated, comprising 69/103 (67%) who received therapy in overt relapse and 34/103 (33%) who were treated in a pre-emptive manner when molecular/cytogenetics recurrence or mixed chimerism occurred. The treatment was donor lymphocyte infusion (DLI)-based for 40/103 (39%) patients. RESULTS: The 1-, 2-, and 5-year OS of patients treated with DLI (n = 40) was 67%, 34%, and 34%, respectively, for those treated preventively (n = 20) and 43%, 20%, and 20%, respectively, for those treated in overt relapse (n = 20) (p < 0.01). The 1-, 2-, and 5-year OS of patients treated without DLI (n = 63) was 54%, 40%, and 26%, respectively, for those treated preventively (n = 14) and 17%, 5%, and 0%, respectively, for those treated in overt relapse (n = 49) (p < 0.01). CONCLUSIONS: Relapse treatment with a pre-emptive strategy was associated with improved outcomes, particularly when DLI was employed.

Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges.

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.

Outcome of Human Parainfluenza Virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.

BACKGROUND: This retrospective study focused on analyzing community-acquired respiratory virus (CARV) infections, in particular human parainfluenza virus (hPIV) after allogeneic stem cell transplant (allo-SCT) in adults recipients. It aimed to assess the impact of ribavirin treatment, clinical characteristics, and risk factors associated with lower respiratory tract disease (LRTD) progression and all-cause mortality. PATIENTS AND METHODS: The study included 230 allo-SCT recipients diagnosed with hPIV between December 2013 and June 2023. Risk factors for the development of LRTD, disease severity, and mortality were analyzed. Ribavirin treatment was administered at physician discretion in 61 out of 230 cases (27%). RESULTS: Risk factors for LRTD progression in multivariate analysis were corticosteroids > 30 mg/day (Odds ratio (OR) 3.5, 95% Confidence Interval (C.I.) 1.3-9.4, p = 0.013), fever at the time of hPIV detection (OR 3.89, 95% C.I. 1.84-8.2, p < 0.001), and absolute lymphocyte count (ALC) < 0.2 × 109/L (OR 4.1, 95% C.I. 1.42-11.9, p = 0.009). In addition, the study found that ribavirin therapy significantly reduced progression to LRTD [OR 0.19, 95% C.I. 0.05-0.75, p = 0.018]. Co-infections (OR 5.7, 95% C.I. 1.4-23.5, p = 0.015) and ALC < 0.2 × 109/L (OR 17.7, 95% C.I. 3.6-87.1, p < 0.001) were independently associated with higher day + 100 after hPIV detection all-cause mortality. There were no significant differences in all-cause mortality and infectious mortality at day + 100 between the treated and untreated groups. CONCLUSION: ALC, corticosteroids, and fever increased the risk for progression to LRTD while ribavirin decreased the risk. However, mortality was associated with ALC and co-infections. This study supports further research of ribavirin therapy for hPIV in the allo-HSCT setting.

Exploring the immunological relevance of pre-transplant donor-specific antibody in intestinal transplantation, with special consideration to the liver.

Despite recent advances that have improved outcomes following intestinal transplantation (ITx), achieving long-term patient survival and rejection-free survival is still challenging. Understanding the relevance of pre-transplant human leukocyte antigen (HLA) donor-specific antibody (DSA) in ITx and the immunomodulatory potential of the liver within the allograft is crucial to providing an accurate assessment of pre-transplant immunological risk, which could influence and improve post-transplant outcomes further. This was the primary objective of this retrospective study of 95 adult ITx transplants which took place at Cambridge University Hospitals (United Kingdom) between 2007 and 2019. Two novel programs were developed and validated to identify DSA (tested by Luminex single antigen beads) in this dataset. Data analysis utilised Kaplan-Meier survival methods, and statistical analysis was performed using log-rank tests and adjusted Cox models. Fifty-four (57%) ITx cases contained a liver, and 36 (38%) were sensitised to HLA. Pre-transplant DSA > 500 mean fluorescent intensity appeared to negatively affect post-ITx patient survival and rejection outcomes. Additionally, liver-inclusive allografts seemed to show particular resistance to HLA class I DSA. Our data hints towards consistency with other ITx studies where deleterious effects of DSA have been demonstrated, and where liver inclusion is protective from HLA class I DSA. This is in line with current national guidelines for immunological risk. Our publicly available research programs could support future large or multicentre studies where statistically relevant data might be gained.

Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical sibling donors for hematological malignancies in 6064 adults from 2003 to 2020: different impacts on survival according to time period.

BACKGROUND: Mobilized peripheral blood stem cells (PBSC) have been widely used instead of bone marrow (BM) as the graft source for allogeneic hematopoietic cell transplantation (HCT). Although early studies demonstrated no significant differences in survival between PBSC transplantation (PBSCT) and BM transplantation (BMT) from human leukocyte antigen (HLA)-identical sibling donors to adults with hematological malignancies, recent results have been unclear. OBJECTIVE: The objective of this retrospective study was to compare overall survival (OS), relapse, non-relapse mortality (NRM), hematopoietic recovery and graft-versus-host disease (GVHD) between PBSCT and BMT according to the time period of HCT (2003-2008, 2009-2014, or 2015-2020). STUDY DESIGN: We retrospectively compared the outcomes after PBSCT versus BMT in 6064 adults with hematological malignancies using a Japanese registry database between 2003 and 2020. RESULTS: The adjusted probability of OS was significantly higher in BMT recipients compared to PBSCT recipients during the early period of 2003-2008 (adjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70-0.91; P < 0.001) and the middle period of 2009-2014 (adjusted HR, 0.80; 95% CI, 0.70-0.91; P < 0.001). However, during the late period of 2015-2020, the adjusted probability of OS was comparable between BMT and PBSCT recipients (adjusted HR, 0.94; 95% CI, 0.79-1.13; P = 0.564), which were mainly due to the reduction of NRM. There was no significant difference in the relapse rate between the groups, irrespective of the time period. Compared to BMT, PBSCT led to faster neutrophil and platelet recovery and the cumulative incidences of grades II-IV and grades III-IV acute and overall and extensive chronic GVHD were significantly higher in PBSCT recipients, irrespective of the time period. CONCLUSIONS: PBSCT and BMT had similar survival outcomes and relapse rates in adult patients with hematological malignancies during the late time period of 2015-2020 despite the hematopoietic recovery and acute and chronic GVHD being higher in PBSCT recipients in all time periods.

Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest collections from the NMDP has shown that bone marrow quality has decreased based on total nucleated cell count in the product. To ensure that quality bone marrow products are available to all recipients, the NMDP Marrow Alliance was formed in April of 2021 to increase the ability for bone marrow collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing bone marrow harvests. This White Paper describes the best practices of performing a bone marrow harvest as defined by the NMDP Marrow Alliance.