[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].

This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.

[Pathogenesis and novel therapies for chronic GVHD].

Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

[Allogeneic transplantation as a therapeutic option for atypical chronic myeloid leukemia].

Atypical chronic myeloid leukemia (aCML) is a rare disease classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Recent advances in gene mutational profiling have clarified the characteristics of aCML as a disease entity relative to other MDS/MPNs. Although some studies suggest the efficacy of DNA demethylating agents and tyrosine kinase inhibitors, data about these agents are limited due to the small number of patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is only therapeutic option that can provide durable remission for aCML and other MDS/MPNs. Retrospective studies from Europe and Japan revealed the clinical results of allo-HSCT for aCML. This review summarizes the pathogenesis of aCML and the development of allo-HSCT and other therapeutic options.

Long-Term Survival and Immune Reconstitution of Donor-Derived Chimeric Antigen Receptor T-Cell Therapy for Childhood Molecular Relapse of B-Cell Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.

Measurable residual disease assessment prior to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and myelodysplastic syndromes: a 20-year monocentric study.

Patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who undergo allogeneic hematopoietic stem-cell transplantation (alloHSCT) can have divergent survival outcomes while all in morphological complete remission (CR). Techniques of measurable residual disease (MRD) have allowed us to refine their prognosis in two categories: MRD-positive and MRD-negative patients. We conducted a monocentric retrospective study (01/2000-12/2020) to assess the prognosis of pretransplant MRD status measured by multiparametric flow cytometry (MFC) and molecular biology assessed by PCR. 192 patients were included. The median follow-up period was 77 months. Among patients undergoing alloHSCT in CR, overall survival (median-OS: 130.6 vs. 16.0 months, P < 0.001), disease-free survival (median-DFS: 109.6 vs. 7.1 months, P < 0.001) and cumulative incidence of relapse (12-month CIR: 7.3% vs. 33.7%, P < 0.0001) were significantly different between MRD-negative and MRD-positive patients. Patients with discordant intermethod results had intermediate DFS. MRD-negative patients according to molecular PCR-based techniques, WT1 overexpression and MFC had longer median-DFS, compared to MRD-positive patients (P = 0.001, P < 0.001, P < 0.001, respectively). Looking into subgroups, MRD-positive patients among the ELN2017 adverse-category (P < 0.0001), myeloablative and reduced-intensity conditioning regimens (P < 0.0001, P = 0.005), < 60-year patients (P < 0.001) and AML patients (P < 0.001) were associated with lower DFS. This difference was not found in ≥ 60-year patients (P = 0.27) and MDS patients (P = 0.70). MRD-positive patients within the favorable/intermediate ELN2017 category trended toward lower DFS (P = 0.05). We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

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

BACKGROUND: Cytomegalovirus (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. METHODS: Using 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. RESULTS: The 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 ß-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. CONCLUSIONS: The 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.

Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

The diagnosis and management of mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive inherited lysosomal storage disease. With pathogenic variants of the IDS gene, the activity of iduronate-2-sulfatase (IDS) is reduced or lost, causing the inability to degrade glycosaminoglycans (GAGs) in cells and influencing cell function, eventually resulting in multisystemic manifestations, such as a coarse face, dysostosis multiplex, recurrent respiratory tract infections, and hernias. Diagnosing MPS II requires a combination of clinical manifestations, imaging examinations, urinary GAGs screening, enzyme activity, and genetic testing. Currently, symptomatic treatment is the main therapeutic approach. Owing to economic and drug availability issues, only a minority of patients opt for enzyme replacement therapy or hematopoietic stem cell transplantation. The limited awareness of the disease, the lack of widespread detection technology, and uneven economic development contribute to the high rates of misdiagnosis and missed diagnosis in China.

Healthcare resource utilization and associated costs in patients with chronic graft-versus-host disease post allogeneic hematopoietic stem cell transplantation in England: HCRU and associated costs in patients with cGvHD in England.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017-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). RESULTS: 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% vs 66.6%; emergency care: 39.3% vs 30.5%; ICU: 7.4% vs 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% vs 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 vs £8,548 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% vs 66.4%; ICU: 7.1% vs 5.4%; outpatient: 87.9% vs 76.7%; emergency care: 44.4% vs 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 vs 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 vs £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. CONCLUSIONS: 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.

Efficacy of nebulized GM-CSF inhalation in preventing oral mucositis in patients undergoing hematopoietic stem cell transplantation: A retrospective study.

Objective: To study the efficacy of oxygen atomization inhalation of granulocyte-macrophage colony-stimulating factor (GM-CSF) for preventing oral mucositis in patients following hematopoietic stem cell transplantation. Methods: Data from patients who received hematopoietic stem cell transplantation and were treated with GM-CSF for the prevention/treatment of oral mucositis in our hospital from June 2021 to June 2023 were collected. The enrolled patients were divided into an observation group and a control group according to the use of GM-CSF. The WHO Mucositis Scale Assessment Criteria were utilized to evaluate the characteristics of patients with oral mucositis (OM) from the beginning of the pretreatment period until they were discharged from the hospital. The general data, preconditioning protocol, transplantation method, overall grade and duration of oral mucositis, pain score, nutritional score and number of days of parenteral nutrition use, oral mucosal infection status and antibiotic use intensity, the granulocyte and megakaryocyte reconstruction time, and adverse reaction reports of the patients were collected and summarized through the medical records system. Results: A total of 143 patients were included in this study, including 75 patients in the observation group. In the observation group, there were 36 males and 39 females aged 22-67 years. There were 45 patients who received autologous transplantation and 30 patients who received allogeneic transplantation. In terms of the disease distribution, there were 33 cases of leukemia, 24 cases of lymphoma, 11 cases of multiple myeloma, and 8 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 2 cases of myelofibrosis, 1 case of POEMS syndrome). There were 68 patients in the control group, including 33 males and 35 females; the control group patients were aged 25-74years. Forty-one patients received autologous transplantation, and 27 patients received allogeneic transplantation. The disease distribution included 29 cases of leukemia, 17 cases of lymphoma, 12 cases of multiple myeloma, and 7 other cases (3 cases of aplastic anemia, 2 cases of myelodysplastic syndrome, 1 case of myelofibrosis, 1 case of POEMS syndrome). There were no significant differences between the two groups concerning age, sex, disease distribution or the transplantation method (P > 0.05). In the observation group, 13 cases did not develop oral mucositis, and 32 cases developed oral mucositis (16 cases of Grade I, 14 cases of Grade II, 2 cases of Grade III, and 0 cases of Grade IV). In the control group, there were 5 cases without mucositis and 36 cases with oral mucositis (6 cases of Grade Ⅰ, 16 cases of Grade Ⅱ, 8 cases of Grade Ⅲ, and 6 cases of Grade Ⅳ), the difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). In the observation group, 8 patients did not develop oral mucositis, and 22 patients developed oral mucositis (13 cases of Grade I, 7 cases of Grade II, 1 case of Grade III, and 1 case of Grade IV). In the control group, 1 case did not develop mucositis, and 26 cases developed oral mucositis (3 cases of Grade Ⅰ, 10 cases of Grade Ⅱ, 9 cases of Grade Ⅲ, and 4 cases of Grade Ⅳ). The difference was statistically significant (P < 0.05). The pain score and duration of mucositis in the observation group were significantly lower than those in the control group (P < 0.05). In addition, the oral mucosal infection rate, antibiotic use intensity, nutritional score, per capita number of days of parenteral nutrition use and hematopoietic reconstruction time in the observation group were significantly lower than those in the control group (P < 0.05). No adverse reactions were reported in either group. Conclusion: In both autologous transplantation and allogeneic transplantation patients, GM-CSF atomized inhalation can improve the prevention and treatment of oral mucositis in stem cell transplantation patients, reduce the incidence of oral infection, reduce the intensity of antibiotic use and the number of days of parenteral nutrition use, and thus promote the process of hematopoietic reconstruction.

Efficacy of Ruxolitinib with corticosteroids in idiopathic pneumonia syndrome post-allogeneic hematopoietic stem cell transplantation: A single-center experience and systematic review.

BACKGROUND: Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature. METHODS: The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25. RESULTS: The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero. CONCLUSION: The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.

Toxoplasma qPCR kinetics to guide pre-emptive treatment of toxoplasmosis after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. METHODS: We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. RESULTS: Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). CONCLUSIONS: This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Allogeneic transplantation for adult T-cell leukemia/lymphoma in adolescent and young adults and young patients: A nationwide retrospective study by the ATL working group of the Japan society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides durable remission for patients with adult T-cell leukemia/lymphoma (ATL); however, few studies have focused on post-transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients <40 years (adolescents and young adult [AYA]; n = 73) and 40-49 years (Young; n = 330), we conducted a nationwide retrospective study. Estimated 3-year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (p = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10-2.39], p = 0.015), chronic graft-versus-host disease (GVHD)-free and relapse-free survival (CRFS) (HR 1.54 [1.10-2.14], p = 0.011), and GVHD-free and relapse-free survival (GRFS) (HR 1.40 [1.04-1.88], p = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens; however, non-relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24-0.86], p = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo-HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.

Chemotherapy and allo-HSCT for young patients with aggressive ATL.

Adult T-cell leukemia-lymphoma (ATL) is an aggressive malignancy with a poor prognosis, especially for patients with the aggressive subtype. While conventional chemotherapy offers short-term disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most promising curative approach for young, transplant-eligible patients. This review focuses on current treatment strategies for aggressive ATL in this specific population. We discuss the rationale for early upfront allo-HSCT following induction chemotherapy. The advent of allo-HSCT using alternative donors, particularly haploidentical HCT, has broadened the applicability of early upfront allo-HSCT in patients with aggressive ATL worldwide. Finally, we address emerging therapies that may improve outcomes in the context of allo-HSCT, paving the way for further advancements in the treatment of aggressive ATL.

The role of auto-HSCT in extranodal natural killer/T cell lymphoma.

Objectives: Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered optional consolidation therapy especially for relapsed/refractory extranodal NK/T-cell lymphoma (ENKL), but its applications to newly diagnosed advanced-stage ENKL is currently limited. Methods: We collected 51 cases of newly diagnosed advanced-stage ENKL patients, including 26 with auto-HSCT and 25 with chemotherapy rather than HSCT, from our hospital between 2014/01 and 2023/12. We summarized the patients' characteristics, conducted survival analysis of the 51 cases, and analyzed the potential benefits of auto-HSCT to ENKL patients. Results: It shows that after a median follow-up time of 39 months, the estimated 5-year overall survival (OS) of the 51 newly diagnosed advanced-stage ENKL patients is 73.4%, and their estimated 5-year progression-free survival (PFS) is 73.4%. For patients receiving auto-HSCT, the 5-year OS (91.7%) and PFS (91.0%) are significantly different from those of patients receiving chemotherapy without HSCT (OS 53.3%, PFS 54.5%) (p < 0.05). Univariate and multivariate analysis results suggest that only the l-asparaginase usage in chemotherapy showed significant impact on the OS, and none of concerned factors showed significant impact on the PFS. Conclusions: Auto-HSCT is indeed an option to newly diagnosed advanced-stage ENKL, but further studies are still required for more strict disease management.

Single-Unit Transfusion Policy in Autologous Hematopoietic Stem Cell Transplantation: Less is Not Worse.

Single-unit red blood cell (1-RBC) transfusion policy has shown to effectively reduce transfusion burden while maintaining comparable clinical outcomes in hematological patients compared to the classical double-unit policy. However, its effects specifically after autologous stem cell transplantation (ASCT) have not been previously studied. We aimed to evaluate the impact of the 1-RBC policy on transfusion burden in a homogeneous cohort of patients undergoing ASCT. We retrospectively compared the transfusion requirements and the clinical outcomes of 187 patients transplanted from May 2019 to December 2022 under a 1-RBC policy, with a historical cohort of 153 patients transplanted from January 2016 to April 2019 under a double-unit policy. The 1-RBC policy was associated with a 32% reduction in RBC utilization and lower number of RBC transfusions at day 30 after transplantation (median 2 versus 3 units; P < .0001), with an odds ratio of 0.49 in multivariate analysis (P = .03). However, the number of transfusion episodes remained similar (median of 2 in both arms; P = .34). No significant differences in length of stay, hemoglobin levels at discharge or 30-day mortality were observed. In conclusion, transitioning to the 1-RBC represents a straightforward action in current practice that significantly reduces blood transfusions in patients undergoing ASCT, without negatively impacting clinical outcomes.

Umbilical cord blood stem cells as third-party adjuvant infusions in human leukocyte antigen antibody-positive patients undergoing haploidentical hematopoietic stem cell transplantation.

Introduction: Graft failure (GF) or poor graft function (PGF) remain critical obstacles in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), especially in recipients with HLA antibodies. Here, we performed a retrospective cohort study to investigate the efficacy and safety of the use of unrelated umbilical cord blood stem cells (UCBs) as a third-party adjuvant infusion in patients with HLA-antibodies undergoing haplo-HSCT. Methods: A total of 90 patients were divided into three groups: 17 patients in Group A (with positive HLA antibodies and who received UCB infusion), 36 patients in Group B (with positive HLA antibodies without UCB infusion), and 37 patients in Group C (without HLA antibody or UCB infusion). Results: The median age of patients included in Groups A, B, and C was 43 (IQR, 27 - 49.5), 33 (IQR, 20 - 48.75), and 30 (IQR, 18 - 46.5) years, respectively. All but one patient in Group B achieved granulocyte recovery within 28 days after transplantation. The median time to granulocyte engraftment were all 12 days for patients in Groups A, B, and C, respectively. All the patients in Group A achieved 100% donor chimerism without UCB engraftment. There were no significant differences in granulocyte or platelet engraftment time between the three groups. There were 1, 5, and 0 patients in Groups A, B, and C, respectively, who developed PGF. The cumulative incidence rates for any grade of acute graft-versus-host disease (aGVHD) were comparable among the three groups. Patients in Group B presented a greater incidence of cGVHD than did those in Group A (P = 0.002) and Group C (P = 0.006). Patients in Group A presented more limited and milder cGVHD than those in Group C (P < 0.0001). The 1-year relapse-free survival (RFS) was 70.6% (95% CI, 0.47 - 0.87), 55.6% (95% CI, 0.40 - 0.70), and 77.9% (95% CI, 0.63 - 0.89) in Groups A, B, and C, respectively. Discussion: Our results indicated that patients who were positive for HLA antibodies were at a greater risk of developing GF/PGF. Co-infusion with UCBs was safe and improved engraftment, cGVHD, and improved the 1-year RFS to some extent.

Prolonged Thrombocytopenia and Severe Transfusion Reaction after ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Chronic Myelomonocytic Leukemia.

Introduction: Major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common practice and represents a challenging transfusion scenario. Prolonged thrombocytopenia with increased platelet transfusion needs is one of its reported adverse effects, and this has been linked to the persistence of recipient anti-donor isoagglutinins. Case Presentation: A 55-year-old male patient, O Rh(D)-positive, with chronic myelomonocytic leukemia underwent major incompatible allo-HCT from a A Rh(D)-negative donor. He presented with prolonged thrombocytopenia and multiple transfusion reactions after A Rh(D)-negative platelet transfusions. Considering the outcomes of numerous examinations, we tested the anti-A1 titers, finding a significant persistence of anti-donor isoagglutinins. We limited platelet transfusions to blood group O Rh(D)-negative donors, which significantly decreased the requirement for platelet transfusions. In addition, the transfusion reactions ceased. Conclusion: In case of transfusion reactions against platelet products in major ABO-incompatible allo-HCT patients, isoagglutinin monitoring should be considered and a change in the platelet transfusion protocol may be beneficial in patients presenting high isotiters against recipient's blood type.

In vivo dosimetry of total body irradiation patients: A 10 year retrospective analysis.

Myeloablative Total Body Irradiation (TBI) used in our Institution, as part of the conditioning scheme for haematopoietic stem cell transplantation, is an extended-distance supine technique that has been implemented using a 15 MV LINAC beam, lead lung compensators, PMMA, and water bolus to improve homogeneity. This study reviews in-vivo dosimetry (IVD) over 10 years of treatments, assessing the technique's robustness, accuracy, and efficiency. A 2-lateral opposite fields plan was calculated from planning CT with validated Oncentra TPS (Elekta AB, Sweden). Monitor units (MUs), lung compensators shape and thickness were calculated to deliver the prescription dose (12 Gy in 6 bi-daily fractions or 9.9 Gy in 3 daily fractions) to the patient's abdomen midline at the umbilical level, maintaining lung dose within ±5 % range of prescription. Data from 103 patients, of which more than 87 % were pediatric, were retrieved and analyzed for a total of 537 treatment fractions. The impact of IVD omission was evaluated, supposing doing it only once or in the first two fractions, if necessary. Median ΔMU from planned was -1.2 %. Median percentage dose deviation from prescription in 6 anatomical regions was below 2 %. IVD omission could have resulted in an increase of 7 patients registering at least one anatomical region outside the ±5 % dose range at the end of treatment. It is possible to confirm the implemented technique's robustness and accuracy in delivering the prescribed dose under IVD monitoring. Nevertheless, this technique and associated IVD are time-consuming and IVD omission could be assessed with limited drawbacks.