Efficacy and Nuances of Precision Molecular Engineering for Hodgkin's Disease to a Gene Therapeutic Approach.

Gene therapy is a particularly useful treatment for nervous system genetic diseases, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease (HD). Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL. HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed disease. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2,5)-derived ALCL genetic treatment for Hodgkin's disease.

[Exploration and practice of novel models of cellular therapy and hematopoietic stem cell transplantation].

Hematopoietic stem cell transplantation provides an effective cure for various hematological diseases, especially malignant hematological diseases, its treatment system has been continuously optimized, the source of donors has been expanding, the indications have been expanding, and the therapeutic effect has also made breakthroughs to a certain extent. At present, the status of hematopoietic stem cell transplantation technology in most hematological diseases is still unshakable, but the recurrence of the primary disease and complications related to hematopoietic stem cell transplantation are still two major clinical challenges that affect the long-term survival and quality of life of patients. Cell therapy represented by chimeric antigen receptor T (CAR-T) has made breakthrough progress in the treatment of refractory/recurrent B-cell malignancies. Compared with traditional drugs, cell therapy has unique in vivo metabolic characteristics, relying on immune specific recognition and the repair ability of stem cells. It is currently emerging in the treatment of blood tumors and the management of transplant complications. Multiple clinical studies have preliminarily demonstrated a new diagnostic and therapeutic model combining cell therapy with hematopoietic stem cell transplantation.

[Haploidentical donor peripheral blood stem cell transplantation using third-party cord blood compared with matched unrelated donor transplantation for patients with hematologic malignancies].

Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

[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.

[Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases].

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

[Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients].

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM (P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM (P=0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection.

Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A-/- mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A-/- immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)-/- female mice and observed a significant reduction in immunopathology in IL17RA-/- mice. WT bone marrow transplants to IL17RA-/- recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.

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.

Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia.

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

Quality of life in the digital age: young adult hematopoietic stem cell transplantation patients and healthcare providers' views of telehealth.

PURPOSE: The COVID-19 pandemic shifted the healthcare field from in-person clinic visits to virtual-based telehealth appointments. This study explored young adult (YA) hematopoietic stem cell transplantation (HSCT) patient and physician communication preferences and quality of life. METHODS: One researcher conducted semi-structured interviews with n = 10 YA HSCT patients and n = 10 healthcare providers (HPs). HPs included physicians (n = 5) and advanced practice provider (APP) (nurse practitioners and physician assistants) (n = 5). Interviews lasted approximately 10-15 min, were held over Zoom®, and were audio-recorded. Interviews were professionally transcribed verbatim, and two independent researchers conducted a thematic analysis using Dedoose®. RESULTS: Common themes included the following: (1) convenience, (2) improved communication, (3) technology issues, and (4) quality of life for patients and physicians. In general, most patients (n = 7; 70%) preferred in-person visits over telehealth for initial appointments, stating they chose the "social connection" and "engagement" associated with in-person visits. For "check-ins" and follow-up appointments (n = 5; 50%), patients preferred hybrid appointments. Physicians (n = 4; 80%) preferred telehealth stating it was "convenient," "timesaving," and improved "compliance." In contrast, all APP staff (n = 5; 100%) preferred in-person visits, stating in-person improved "relationships" with patients and was more "convenient" than using electronic devices for telehealth. CONCLUSION: Providers differed in preference. APP personnel preferred in-person visits and HSCT physicians preferred telehealth appointments. YA HSCT patients preferred in-person for initial appointments and hybrid clinic visits for follow-up appointments.

HLA molecular mismatches and induced donor-specific tolerance in combined living donor kidney and hematopoietic stem cell transplantation.

Introduction: We investigated the potential role of HLA molecular mismatches (MM) in achieving stable chimerism, allowing for donor-specific tolerance in patients undergoing combined living donor kidney and hematopoietic stem cell transplantation (HSCT). Methods: All patients with available DNA samples (N=32) who participated in a phase 2 clinical trial (NCT00498160) where they received an HLA mismatched co-transplantation of living donor kidney and facilitating cell-enriched HSCT were included in this study. High-resolution HLA genotyping data were used to calculate HLA amino acid mismatches (AAMM), Eplet MM, three-dimensional electrostatic mismatch scores (EMS-3D), PIRCHE scores, HLA-DPB1 T-cell epitope group MM, HLA-B leader sequence MM, and KIR ligands MM between the donor and recipient in both directions. HLA MM were analyzed to test for correlation with the development of chimerism, graft vs. host disease (GvHD), de novo DSA, and graft rejection. Results: Follow-up time of this cohort was 6-13.5 years. Of the 32 patients, 26 developed high-level donor or mixed stable chimerism, followed by complete withdrawal of immunosuppression (IS) in 25 patients. The remaining six of the 32 patients had transient chimerism or no engraftment and were maintained on IS (On-IS). In host versus graft direction, a trend toward higher median number of HLA-DRB1 MM scores was seen in patients On-IS compared to patients with high-level donor/mixed chimerism, using any of the HLA MM modalities; however, initial statistical significance was observed only for the EMS-3D score (0.45 [IQR, 0.30-0.61] vs. 0.24 [IQR, 0.18-0.36], respectively; p=0.036), which was lost when applying the Bonferroni correction. No statistically significant differences between the two groups were observed for AAMM, EMS-3D, Eplet MM, and PIRCHE-II scores calculated in graft versus host direction. No associations were found between development of chimerism and GvHD and non-permissive HLA-DPB1 T-cell epitope group MM, HLA-B leader sequence, and KIR ligands MM. Conclusion: Our results suggest an association between HLA-DRB1 molecular mismatches and achieving stable chimerism, particularly when electrostatic quality of the mismatch is considered. The non-permissive HLA-DPB1 T-cell epitope group, HLA-B leader sequence, and KIR ligands MM do not predict chimerism and GvHD in this combined kidney/HSCT transplant patient cohort. Further work is needed to validate our findings. Clinical trial registration: https://clinicaltrials.gov/study/NCT00498160, identifier NCT00498160.

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma.

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. RESULTS: The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37-69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046-8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217-13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. CONCLUSIONS: This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

[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.

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.

Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Factors Influencing Life Space Mobility in Cancer Survivors Following Hematopoietic Stem Cell Transplantation - Physical Function, Depression, Fatigue, Neighborhood Walkability, and Employment Status.

BACKGROUND/OBJECTIVE: The level of physical activity in the daily lives of cancer survivors following hematopoietic stem cell transplantation (HSCT) is crucial for maintaining their physical and mental health. Considering that life space mobility (LSM) may limit physical activity, maintaining and expanding LSM is particularly essential for post-HSCT survivors. This study aimed to identify factors influencing LSM in post-HSCT survivors. METHODS: Thirty cancer survivors after HSCT (14 women, mean age 52.0 ± 12.3 years, 196-3017 days post-HSCT) were included in this cross-sectional study. The assessment encompassed patient characteristics, employment status, life space (Life Space Assessment; LSA), physical function (handgrip strength, isometric knee extension strength, 5 chair standing test, walking speed), depression (Self-rating Depression Scale; SDS), fatigue (Cancer Fatigue Scale), and neighborhood walkability (Walk Score®). The association between LSA and each factor was compared by correlation analysis. Subsequently, multiple regression analysis was conducted, with LSA as the dependent variable and independent variables being outcome measures exhibiting a significant correlation with LSA. RESULTS: Variables significantly correlated with LSA included SDS (r =-0.65, p < .01), employment status (r=-0.60, p < .01), handgrip strength (r = 0.43, p = .02), and isometric knee extension strength (r = 0.40, p = .03). Results of multiple regression analysis show that SDS (ß = -0.53, p < .01), employment status (ß = 0.48, p < .01), and isometric knee extension strength (ß = 0.27, p = .02) were significantly associated with LSA (R2 = 0.74). CONCLUSION: Depression, employment status, and isometric knee extension strength were identified as factors related to LSM in post-HSCT survivors.

[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

[Guideline for the diagnosis and management of multiple myeloma-related renal impairment (2024 version)].

Renal impairment is a common complication of multiple myeloma (MM). All patients with MM should be assessed for the presence and severity of renal impairment. The clinicopathological manifestations of MM-related renal impairment are diverse and complex; accordingly, except for light-chain nephropathy, which can often be diagnosed without biopsy based solely on clinical criteria, a renal biopsy is needed for an accurate diagnosis. Supportive care, such as adequate hydration, is required for all patients with MM-related renal impairment. The guideline provide the principles for dose adjustment of the drugs used for MM with renal impairment, including proteasome inhibitors, immunomodulators, monoclonal antibodies, small molecule inhibitors, and alkylating agents, as well as those used for myeloma bone disease. Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell immunotherapy (CAR-T) are effective in patients with moderate renal impairment and are tolerated by the patients. The Chinese Hematology Association; the Chinese Geriatrics Association, Society of Hematology; and the Chinese Research Hospital Association, Society of Nephrology asked experts to collate information on current progress in clinical research relating to MM with renal impairment. This guideline was developed based on the gathered data combined with the latest international consensus and clinical practice guidelines.

[Advances in nutritional support for children undergoing hematopoietic stem cell transplantation]. / é€ è¡€å¹²ç»†èƒžç§»æ¤å„¿ç«¥çš„è¥å »æ”¯æŒè¿›å±•.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for various potentially life-threatening malignant and non-malignant diseases in children, such as malignancies, immunodeficiency syndromes, severe aplastic anemia, and inherited metabolic disorders. During transplantation, many factors can affect the nutritional status of the children, including radiotherapy, chemotherapy, gastrointestinal disorders, graft-versus-host disease, and medications. Malnutrition has been associated with decreased overall survival and increased complications in children undergoing HSCT, making nutritional support a crucial component of their management. However, currently, there is a lack of guidelines or consensus on nutritional support for children undergoing HSCT in China. Therefore, this review summarizes the progress in nutritional support for children undergoing HSCT, aiming to provide clinical guidance.