Search

Abstract: Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days and then twice weekly through day 30. The primary end point was to determine 3-, 7-, and 30-day post-CAR T-cell infusion hospitalizations. Early CRS intervention involved administering tocilizumab as an outpatient for grade ≥1 CRS. Fifty-eight patients received outpatient CAR T-cell infusion (33 myeloma, 24 lymphoma, and 1 acute lymphoblastic leukemia). Of these, 17 (41%), 16 (38%), and 9 patients (21%) were admitted between days 0 to 3, 4 to 7, and 8 to 30 after CAR T-cell infusion, respectively. The most common reason for admission was CAR T-cell-related toxicities (33/42). Hospitalization was prevented in 15 of 35 patients who received tocilizumab for CRS as an outpatient. The nonrelapse mortality rates were 1.7% at 1 month and 3.4% at 6 months. In conclusion, we demonstrate that the administration of commercial CAR T-cell therapies in an outpatient setting is safe and feasible without intensive remote monitoring using an early CRS intervention strategy., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Relying on our experience on the development of data registration and management systems for clinical and biological data coming from patients with hematological malignancies, as well as on the design of strategies for data collection and analysis to support multi-center, clinical association studies, we designed a framework for the standardized collection and transformation of clinically relevant real-world data into evidence, to meet the challenges of gathering biomedical data collected during daily clinical practice in order to promote basic and clinical research.

Background: CAR-T therapy has emerged as a potentially effective treatment for individuals diagnosed with hematologic malignancies. Understanding patients' unique experiences with this therapeutic approach is essential. This knowledge will enable the development of tailored nursing interventions that align with the increasing importance of patient-centered care., Objective: To examine and synthesize qualitative data on patients and their family caregivers' experiences during the treatment journey., Design: We conducted a systematic review and qualitative meta-synthesis. Eligible studies contained adult patient or family caregiver quotes about experiences of CAR-T therapy, published in English or Chinese in a peer-reviewed journal since 2015. Data sources included MEDLINE, CINAHL, Embase, PsycINFO, Web of Science, Scopus, Cochrane Library, CNKI, and WanFang., Methods: Systematic search yielded 6373 identified articles. Of these, 12 reports were included in the analysis, which covered 11 separate studies. Two reviewers independently extracted data into NVIVO 12.0. Qualitative meta-synthesis was performed through line-by-line coding of full text, organization of codes into descriptive themes, and development themes., Results: The qualitative meta-synthesis yielded eight primary themes. Noteworthy revelations from patients and their family caregivers regarding the CAR-T therapy journey encompassed various aspects. Prior to CAR-T therapy, patients experienced a lack of actual choice, struggled with expectations for treatment outcomes, and encountered intricate emotional experiences. During or immediately after CAR-T therapy, patients reported both comfortable and uncomfortable experiences. Additionally, patients emphasized that concerns regarding treatment efficacy and adverse reactions intensified treatment-related distress. After CAR-T therapy, significant changes were observed, and the burden of home-based rehabilitation. Additionally, we found factors contributed to the high CAR-T therapy cost., Conclusions: To ensure the safety and sustainability of CAR-T therapy, it is crucial to address the physical and psychological aspects of the patient's experience. Effective communication and comprehensive management are highly valued by patients and their caregivers. Further research should investigate ways to reduce burdens and develop self-management education programs for patients and their families., (© 2024. The Author(s).)

Over the past decade, chimeric antigen receptor T cells have emerged as a breakthrough cancer therapy in selected hematologic malignancies. Translating the success of this therapy to solid tumors is challenging. In this issue, we discuss strategies potentially useful to increase the chimeric antigen receptor T-cell efficacy in this clinical indication. See related article by Fischer-Riepe et al., p. 3564., (©2024 American Association for Cancer Research.)

Immunocompromised patients are at high risk to fail clearance of SARS-CoV-2. Prolonged COVID-19 constitutes a health risk and a management problem as cancer treatments often have to be disrupted. As SARS-CoV-2 evolves, new variants of concern have emerged that evade available monoclonal antibodies. Moreover, antiviral therapy promotes SARS-CoV-2 escape mutations, particularly in immunocompromised patients. These patients frequently suffer from prolonged infection. No successful treatment has been established for persistent COVID-19 infection. Here, we report on a series of 21 immunocompromised patients with COVID-19-most of them hematologic malignancies-treated with plasma obtained from recently convalescent or vaccinated donors or a combination thereof. Repeated dosing of SARS-CoV-2-antibody-containing plasma could clear SARS-CoV-2 infection in 16 out of 21 immunocompromised patients even if COVID-19-specific treatments failed to induce sustained viral clearance or to improve clinical course of SARS-CoV-2 infection. Ten patients were major responders defined as an increase delta(d)Ct of > = 5 after the first administration of convalescent and/or vaccinated plasma (C/VP). On average, SARS-CoV-2 PCR Ct values increased from a median value of 22.55 (IQR = 19.10-24.25) to a median value of 29.57 (IQR = 27.55-34.63; p = <.0001) in the major response subgroup. Furthermore, when treated a second time with C/VP, even 4 out of 5 of the initial nonresponders showed an increase in Ct-values from a median value of 23.13 (IQR = 17.75-28.05) to a median value of 32.79 (IQR = 31.75-33.75; p = .013). Our results suggest that C/VP could be a feasible treatment of COVID-19 infection in patients with hematologic malignancies who did not respond to antiviral treatment., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies., Main Body: CIK cells consist of CD3 + /CD56 +  natural killer (NK) T cells, CD3 - /CD56 + NK cells, and CD3 + /CD56 - cytotoxic T cells. In this regard, the CD3 + /CD56 +  NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings., Conclusion: CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies., (© 2024. The Author(s).)

Abstract: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic strategy for eradicating human cancers. Their therapeutic success and durability of clinical responses hinges, in large part, on their functional capacity, including the ability of these engineered cells to simultaneously expand and persist after infusion into patients. CD19 CAR T-cell polyfunctionality, assessing the simultaneous functions of cytokine production, proliferation, and cytotoxicity has been reported to correlate with clinical outcomes. Assay optimization is potentially limited by the heterogeneous nature of CAR T-cell infusion products and target specificity. We optimized a single-cell platform for polyfunctionality using CAR T-cell products manufactured from healthy donors, engineered against a novel target, B-cell-activating factor receptor (BAFF-R) and validated the protocol using CD19 CAR T cells. We observed distinct qualitative differences between BAFF-R and CD19 CAR T cells relative to the proportions of stimulatory vs effector cytokines, based on target antigen density, and, generally, CD19 CAR T cells exhibited lower indices of polyfunctionality. Finally, we applied our assay to the autologous BAFF-R CAR T-cell product generated from the first patient with non-Hodgkin lymphoma treated in an ongoing clinical trial who had progressed after prior CD19 CAR T-cell therapy. We observed robust indicators of polyfunctionality, which correlated with successful CAR T-cell expansion after infusion and achievement of durable complete remission ongoing after 18 months. The precise identification of factors determining the role of BAFF-R CAR T-cell fitness in toxicity and clinical outcome will require the application of this robust assay in the analysis of additional treated patients. This trial was registered at www.ClinicalTrials.gov as #NCT05370430., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset of patients achieving prolonged disease control. This review explores the mechanisms underlying autologous CAR-T therapies and BsAbs, focusing on their clinical application in multiple myeloma, ALL, and non-Hodgkin lymphoma. We provide comprehensive insights into their individual efficacy, limitations concerning broad application, and the potential of combination therapies. These upcoming strategies aim to propel the field forward, paving the way for safer and more effective therapeutic interventions in hematological malignancies., Competing Interests: Declaration of interests S.A.H. reports receiving consulting fees from Jansen, Pfizer, Sanofi, and Galapagos, and research funding from the International Myeloma Society and Alexion. H.E.H. has equity in Allovir and Marker Therapeutics, has served on advisory boards for Tessa Therapeutics, March Biosciences, GSK, Kiadis, and Fresh Wind Biotechnologies, and received research support from Tessa Therapeutics and Kuur Therapeutics. M.K.B. has equity in Allovir, Marker Therapeutics, March Biosciences, and Tessa Therapeutics, has served on advisory boards for Walking Fish Therapeutics, CellGenix GmbH, Marker Therapeutics, Tessa Therapeutics, Abintus, Allogene, Bellicum Pharmaceuticals, Bluebird Bio, Athenex, Memgen, Turnstone Biologics, Coya Therapeutics, TScan Therapeutics, Onkimmune, Poseida Therapeutics, Allovir, Triumvira, MEMGEN, Adaptimmune, and AstraZeneca, and received research support from Tessa Therapeutics. M.S. was a scientific consultant for Tessa Therapeutics and received research support from Tessa Therapeutics and AstraZeneca. Disclosure of outside interests for CAGT investigators: BCM (https://www.bcm.edu/academic-centers/cell-and-gene-therapy/research/disclosure-of-outside-interests)., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Embryonic and fetal hematopoietic stem and progenitor cells differ in some key properties from cells that are part of the adult hematopoietic system. These include higher proliferation and self-renewal capacity, different globin gene usage, and differing lineage biases. Although these evolved to cover specific requirements of embryonic development, they can have serious consequences for the pathogenesis of hematologic malignancies that initiate prebirth in fetal blood cells and may result in a particularly aggressive disease that does not respond well to treatments that have been designed for adult leukemias. This indicates that these infant/pediatric leukemias should be considered developmental diseases, where a thorough understanding of their unique biology is essential for designing more effective therapies. In this review, we will highlight some of these unique fetal properties and detail the underlying molecular drivers of these phenotypes. We specifically focus on those that are pertinent to disease pathogenesis and that may therefore reveal disease vulnerabilities. We have also included an extensive description of the origins, phenotypes, and key molecular drivers of the main infant and pediatric leukemias that have a known prenatal origin. Importantly, successes in recent years in generating faithful models of these malignancies in which cellular origins, key drivers, and potential vulnerabilities can be investigated have resulted in uncovering potential, new therapeutic avenues., Competing Interests: Conflict of Interest Disclosure The authors do not have any conflicts of interest to declare in relation to this work., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Opinion Statement: Cardiac dysfunction is a serious adverse effect of cancer therapies that can interfere with quality of life and impact long-term survival in patients with cancer. Hematopoietic cell transplantation is a potentially curative therapy for many advanced hematologic malignancies and bone marrow failure syndromes, however is associated with several short- and long-term adverse effects, including importantly, cardiovascular toxicities. The goal of this review article is to describe the cardiovascular events that may develop before, during, and after hematopoietic cell transplantation, review risk factors for short- and long-term cardiovascular toxicities, discuss approaches to cardiovascular risk stratification and evaluation, and highlight the research gaps in the consideration of cardiovascular disease in patients undergoing hematopoietic cell transplantation. Further understanding of cardiovascular events and the factors associated with cardiovascular disease will hopefully lead to novel interventions in managing and mitigating the significant long-term burden of late cardiovascular effects in transplant survivors., (© 2024. The Author(s).)

Over the past 30 years the incorporation of monoclonal antibody (mAb) treatments into the management of hematologic malignancies has led to significant improvements in patient outcomes. The key limitation of mAb treatments is the necessity for target antigen presentation on major histocompatibility complex (MHC) and costimulatory molecules to elicit a cytotoxic immune response. With the advent of bispecific antibodies (BsAbs), these limitations can be overcome through direct stimulation of cytotoxic T cells, thus limiting tumor cell evasion. BsAbs are rapidly being incorporated into treatment regimens for hematologic malignancies, and there are now seven FDA-approved treatments in this class, six of which have been approved in the past year. In this review we describe the function, complications, and clinical trial data available for CD3 BsAbs in the treatment of lymphoma, myeloma, and leukemia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite Peng and colleagues providing an extensive review of the clinical and laboratory aspects of CAR-T-associated coagulopathy, the current literature often lacks specificity in nomenclature and gradings, and the clinical implications of coagulopathy may remain unclear. Clear recommendations on stratification and prophylaxis are still required to standardize the clinical approach to this topic. Commentary on: Peng et al. Coagulation abnormalities associated with CAR-T therapy in hematological malignancies: A review. Br J Haematol 2024;205:420-428., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Immune response to vaccinations is dampened in patients with indolent lymphomas due to disease and treatment-related factors. The study by Lim et al. demonstrated impaired humoral response but intact cellular response to the SARS-CoV2 vaccine in patients with follicular lymphoma receiving front-line therapy. The results highlight the importance of several factors in predicting immune response to vaccination and provide estimates of immune response for different clinical scenarios and treatment points. Commentary on: Lim et al. Immunogenicity of COVID-19 vaccines in patients with follicular lymphoma receiving frontline chemoimmunotherapy. Br J Haematol 2024;205:440-451., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I 2 ) in patients with HM., Methods: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16 INK4a expression using the OSU&#95;Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I 2 ) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I 2 ., Results: Age-adjusted p16 INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16 INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09-0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11-0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I 2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16 INK4a [AUC = 0.76, 95% CI (0.56-0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54-0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55-0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57-0.88); p =  < 0.01] measures showed the greatest potential to identify clinical frailty using the I 2 ., Conclusions: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM., Implications for Cancer Survivors: We developed the I 2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM., (© 2024. The Author(s).)

Introduction: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial., Methods: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles., Results: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase., Conclusion: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice., (© 2024 John Wiley & Sons Ltd.)

Chimeric antigen receptor (CAR)-T-cell therapy has demonstrated considerable efficacy and safety in the treatment of patients with relapsed/refractory haematological malignancies. Owing to significant advances, CAR-T-cell therapeutic modality has undergone substantial shifts in its clinical application. Coagulation abnormalities, which are prevalent complications in CAR-T-cell therapy, can range in severity from simple abnormalities in coagulation parameters to serious haemorrhage or disseminated intravascular coagulation associated with life-threatening multiorgan dysfunction. Nonetheless, there is a lack of a comprehensive overview concerning the coagulation abnormalities associated with CAR-T-cell therapy. With an aim to attract heightened clinical focus and to enhance the safety of CAR-T-cell therapy, this review presents the characteristics of the coagulation abnormalities associated with CAR-T-cell therapy, including clinical manifestations, coagulation parameters, pathogenesis, risk factors and their influence on treatment efficacy in patients receiving CAR-T-cell infusion. Due to limited data, these conclusions may undergo changes as more experience accumulates., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative - 46 cases (57%), myeloablative - in 18 (22%) and reduced intensity - 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor's age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) - 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge., (© 2024. The Author(s).)

There is no consensus on second allogeneic stem cell transplantation (alloSCT) indications in patients with hematologic malignancies relapsing after a first alloSCT. In historic publications, a very high non-relapse mortality (NRM) has been described, arguing against performing a second alloSCT. We analysed the outcome of 3356 second alloSCTs performed 2011-21 following a hematologic malignancy relapse. Outcomes at two years after second alloSCT were: NRM 22%, relapse incidence 50%, overall survival 38%, and progression-free survival 28%. Key risk factors for increased NRM were: older age, low performance score, high disease-risk-index, early relapse after the first alloSCT, unrelated/haploidentical donor, and GVHD before second alloSCT. Any type of GVHD after first alloSCT was also important risk factor for acute GVHD and chronic GVHD after second alloSCT. There was a preferential use of a different donor (80%) at second alloSCT from first alloSCT. However, in multivariate analysis, the use of the same alloSCT donor for second alloSCT vs. a different donor was not associated with any of the survival or GVHD endpoints. We show considerably improved outcome as compared to historic reports. These current data support a wider use of second alloSCT and provide risk factors for NRM that need to be considered., (© 2024. The Author(s).)

Evidence-based literature recognizes that the different degrees of agreement between a child self-report and a proxy-report depend on the characteristics of the domains, the child's age and illness, the proxy's own perspective on QoL, and family attendance during the child's hospitalization. This study aims to determine the degree of agreement between proxy-reports and child self-reports on quality of life (QoL) for children with hematologic malignancy ranging in age from 5 to 18 years who are undergoing treatment. We retrieved clinical QoL data from a study titled "Dynamic change in QoL for Vietnamese children with hematologic malignancy" from April 2021 to December 2022. To evaluate the magnitude of agreement between self-reports and proxy-reports, intraclass correlation coefficients (ICCs) for 259 pairs of measurements were quantified. Using independent t tests, the mean differences between self-reports and proxy-reports were tested. Moderate agreement was consistent through all age groups for five subscales, including physical, psychosocial, pain, nausea, and procedural anxiety (ICCs ranged from 0.53 to 0.74). The weakest agreement appeared in two groups, subjects aged 5-7 years and 13-18 years on six domains (school, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication) (-0.01 to 0.49). Child self-rating was consistently higher than that of proxies for the physical, emotional, and nausea domains among children aged 5-7 years and for procedural anxiety, treatment anxiety, and cognitive problems among children aged 8-12 years.    Conclusion: The agreement level of self-reports and proxy-reports was differently distributed by child age and the PedsQL domains. The proxy children agreement on QoL among children with hematologic malignancy was divergent according to the different age groups, which could potentially be explained by proxy-child bonding at different stages of childhood development. Our recommendation for future studies is to explore children's age as a potential factor influencing proxy agreement on QoL among children with cancer. What is Known: • Children and their proxies may think differently about quality of life (QoL). • Comparing two sources of data (i.e., child and proxy) on aspects of QoL can help identify the discrepancies between children's perceptions of their QoL and their parents' perceptions. This can be useful in terms of identifying potential areas for improvement or concern and may also be helpful in making decisions about treatment and care. What is New: • Our study results demonstrated that proxies who comprised children aged 5-7 years or 13-18 years reported differently among domains that cannot be expressed verbally or with body language, including cognitive problems, perceived physical appearance, and communication. • Children generally perceived their QoL to be better than their proxies. Therefore, a more comprehensive understanding of children's QoL may require the consideration of multiple sources of data from various perspectives., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of patients with relapsed/refractory B-cell-derived hematologic malignancies. To date, six CAR T-cell therapies, targeting either CD19 or B-cell maturation antigen, have received regulatory approval. Along with the promising survival benefit, CAR T-cell therapy is associated with potentially life-threatening adverse events, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. While clinical trials evaluating CAR T-cell therapy consistently report the incidence of these adverse events, most trials do not collect health-related quality of life (HRQoL) data. As such, the impact of the CAR T-cell therapy process and related adverse events on the physical and psychological well-being of patients remains uncertain. HRQoL and other patient-reported outcome (PRO) assessments in patients with relapsed or refractory hematologic malignancies are of utmost importance, as individuals may have unmet needs and a high demand for tolerable therapy if a cure is not obtained. In addition, it is important to standardize methods of data collection to better assess the impact of CAR T-cell therapy on quality of life, optimize patients' care and costs, and enable comparisons between different studies. We conducted a literature search up to June 2023 to identify the HRQoL tools used in clinical trials and in real-world studies investigating CAR T-cell therapy in patients with lymphomas or leukemias. In the present comprehensive review, we summarize the most commonly used CAR T-cell specific and non-specific HRQoL tools and discuss how the use of HRQoL and other PRO tools may be optimized.

Reduced-toxicity conditioning (RIC) regimens are used for allogeneic hematopoietic stem cell transplantation in older patients. However, successful outcomes are hindered by graft-versus-host disease (GVHD), treatment-related mortality, and relapse, particularly after haploidentical donor hematopoietic stem cell transplantation (HID-HSCT). The aim of this study was to evaluate the effectiveness of an RIC conditioning regimen that included a combination of cyclosporin A, methotrexate (on day + 1), mycophenolate, lower doses of post-transplantation PTCy (40 mg/kg on day + 3), and ATG (7.5 mg/kg) as GVHD prophylaxis prior to haplo-stem cell transplantation (haplo-SCT) in older patients., Methods: We retrospectively analyzed outcomes in 55 patients ≥ 55 years of age with hematologic malignancies treated with fludarabine, cytarabine, busulfan, and low-dose cyclophosphamide as the conditioning regimen between January 1, 2019, and November 30, 2023., Results: Neutrophil engraftment was successful in all patients within 28 days, with 54 patients (98.2%) achieving complete donor chimerism. The cumulative incidence of non-relapse mortality was 0% at 30 days, 7.5% at 100 days, and 19% at 1 year. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 25% (95%CI, 15-38%), whereas that of grade III-IV aGVHD was 9.1% (95% CI, 3.3-19%). The cumulative incidence of extensive chronic graft-versus-host disease at 1 year was 3.6% (95%CI, 0.66-11%). The cumulative incidences of relapse, overall survival, and GVHD-free/relapse-free survival at 1 year were 9.0%, 71.6%, and 67.1%, respectively., Conclusions: An RIC conditioning regimen, including a combination of lower PTCy/ATG as GVHD prophylaxis, followed by haplo-SCT, might be a promising option for appropriately selected older patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described., Methods: Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression., Results: 178 patients were included (median age 55y [42-64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3-3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11-5.97) and viral load (OR 1.88 per Log; 95%CI 1.29-2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05-6.16), mechanical ventilation (OR 4.11; OR 1.77-10.54) and viral load (OR 1.77 per Log; 95%CI 1.23-2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality., Conclusion: In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome., Competing Interests: Declaration of competing interest M. Darmon report having received consulting fees from Sanofi and Gilead-Kite, research support from MSD, and speaker fees from MSD, Gilead-Kite and Astellas. Elie Azoulay has received fees for lectures from Gilead, Pfizer, Baxter and Alexion. His research group has been supported by Ablynx, Ficher & Payckle, Jazz Pharma, and MSD. The other authors declare having no conflict of interest related to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population., Methods: This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21 years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy., Results: Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p < .001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR] = 2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR = 4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR = 4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p = .001), but not when unrelated to neutropenia (p = .88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR = 1.20, 95% CI: 0.7-2.1)., Conclusions: We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Primary graft failure (PGF) and multi-lineage cytopenia (MLC) increase the risk of nonrelapse mortality in allogeneic hematopoietic cell transplants (HCT). We evaluated the impact of post-transplant cyclophosphamide (PTCy) and splenomegaly on PGF and MLC for hematological malignancies. This study included patients with PTCy (N=84) and conventional graft-vs.-host disease prophylaxis (N=199). The occurrence of splenomegaly varied widely, ranging from 17.1 % (acute myeloid leukemia) to 66.7 % (myeloproliferative neoplasms). Ten patients (N=8 in the PTCy and N=2 in the non- PTCy) developed PGF, and 44 patients developed MLC (both N=22). PTCy and severe splenomegaly (≥20 cm) were risk factors for PGF (odds ratio (OR): 10.40, p<0.01 and 6.74, p=0.01 respectively). Moreover, severe splenomegaly was a risk factor for PGF in PTCy patients (OR: 10.20, p=0.01). PTCy (hazard ratio (HR) 2.09, p=0.02), moderate (≥15, <20 cm, HR 4.36, p<0.01), and severe splenomegaly (HR 3.04, p=0.01) were independent risk factors for MLC. However, in subgroup analysis in PTCy patients, only mild splenomegaly (≥12, <15 cm, HR 4.62, p=0.01) was a risk factor for MLC. We recommend all patients be screened for splenomegaly before HCT, and PTCy is cautioned in those with splenomegaly., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest TT reports honoraria from Pfizer, Otsuka, MSD, Chugai, bbi, Astellas, outside the submitted work. SF has received honoraria from Bristol-Myers-Squibb, Astellas, Nipppon Shinyaku, Otsuka, Pfizer, Novartis, MSD, Sanofi, Janssen, SymBio, Kyowa Hakko Kirin, AstraZeneca, CSL Behring, Meiji Seika Pharma, AbbVie, Takeda, and Chugai Pharma, and received research funding from Shionogi, Kyowa Hakko Kirin, Chugai Pharma, Otsuka, Asahi-Kasei, and Daiichi Sankyo, outside the submitted work. HN reports honoraria from Novartis and Daiichi-Sankyo, scholarship from Daiichi-Sankyo, Cellgene, Chugai, Nihon-Shinyaku, Astellas, Asahikasei-pharma, Chugai, Takeda, Pfizer, and Eisai, outside the submitted work. The other authors have no conflict of interest., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer., Methods: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars., Results: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects., Conclusions: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Tixagevimab and cilgavimab (EVA, Evusheld®), monoclonal antibody combination treatments, consisted of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EVA showed prophylactic and therapeutic effects against coronavirus disease 2019. The Japanese Society of Hematology recommended EVA for such patients with active treatment, but each institution decided on comprehensive administration. We develop a systematic procedure for comprehensive EVA injection prophylactically in patients with hematological malignancies without any over/under-indication. We listed all patients with the required indications from November 2022 to March 2023. We included 178 cases, 84 females and 94 males, with a median age of 70 (range: 19-90) years. Underlying diseases are myeloid neoplasms in 36 (20%), lymphoid neoplasms in 75 (73%), and others. Indications were intensively hematological malignancy treatment, rituximab treatment within 12 months, burton kinase inhibitor treatment, after chimeric antigen receptor T cell immunotherapy, and after stem cell transplantation in 74 (41%), 73 (41%), 3 (2%), 5 (3%), and 23 (13%) cases, respectively. Of the 178 cases, 22 (12.4%) refused EVA injection. Further, 42 and 136 cases were administered outpatient and inpatient, respectively. Over 95% of the listed cases received EVA injection within 3 months. No severe toxicities were observed among them (N = 156), and 8 (5.2%) cases had breakthrough SARS-CoV-2 infection, which was significantly lower (P = 0.02) than those without EVA (4 [18.2%] of 22 cases). Both groups showed no moderate or severe infection cases. This single-center experience showed that comprehensive EVA injection management effectively generated safer completion with preferable clinical impact., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Summarize the latest research of both stem cell transplantation and cellular therapy and present the implications with respect to persons with HIV (PWH), hematologic malignancies, and HIV-1 cure., Recent Findings: Allogeneic (alloSCT) and autologous (autoSCT) stem cell transplantation have been shown to be well tolerated and effective regardless of HIV-1 status. AlloSCT leads to a decrease in the HIV-1 latently infected reservoir orders of magnitude below that achieved with antiretroviral therapy (ART) alone. Utilization of CCR5Δ2/Δ32 donors in an alloSCT has resulted in HIV-1 cures. In the last 12 months, three cases of cure have been published, giving further insight into the conditions required for HIV-1 control. Other advances in the treatment of hematological cancers include chimeric antigen receptor T-cell (CART) therapy, which are active in PWH with lymphoma., Summary: Here we discuss the advances in SCT and cellular therapy in PWH and cancer. Additionally, we discuss how these technologies are being utilized to achieve HIV-1 cure., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

CD123 "expression" is common in hematological malignancies, including acute lymphoblastic leukemia (ALL). Flotetuzumab is a novel, investigational CD3/CD123 DART®. We conducted a phase 1 study evaluating safety and efficacy of flotetuzumab in relapsed/refractory ALL (Cohort A) and other advanced CD123-positive hematological malignancies (excluding myeloid malignancies) (cohort B). Thirteen patients (9 in Cohort A and 4 in Cohort B) were treated at dose level 1 (500 ng/kg/day) before early closure due to discontinuation of drug development by sponsor. Two dose limiting toxicities (Grade 4 thrombocytopenia and neutropenia) occurred in one patient in Cohort B. Cytokine release syndrome occurred in most patients (85%), all being grade ≤2. Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin's lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies.

There have been several clinical studies using chimeric antigen receptor (CAR)-T cell therapy for different hematological malignancies. It has transformed the therapy landscape for hematologic malignancies dramatically. Nonetheless, in acute myeloid leukemia (AML) and T cell malignancies, it still has a dismal prognosis. Even in the most promising locations, recurrence with CAR-T treatment remains a big concern. Oncolytic viruses (OVs) can directly lyse tumor cells or cause immune responses, and they can be manipulated to create therapeutic proteins, increasing anticancer efficacy. Oncolytic viruses have been proven in a rising number of studies to be beneficial in hematological malignancies. There are limitations that cannot be avoided by using either treatment alone, and the combination of CAR-T cell therapy and oncolytic virus therapy may complement the disadvantages of individual application, enhance the advantages of their respective treatment methods and improve the treatment effect. The alternatives for combining two therapies in hematological malignancies are discussed in this article., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m 2 ) was administered for 7 days, followed by GO (3 mg/m 2 ) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Opioids are essential for treating pain in hematologic malignancies (HM), yet are heavily stigmatized in the era of the opioid epidemic. Stigma and negative attitudes towards opioids may contribute to poorly managed cancer pain. We aimed to understand patient attitudes towards opioids for HM pain management, particularly among historically marginalized populations., Methods: We interviewed a convenience sample of 20 adult patients with HM during outpatient visits at an urban academic medical center. Semi-structured interviews were audio-recorded, transcribed, and qualitatively analyzed using the framework method., Results: Among 20 participants, 12 were female and half were Black. Median age was 62 (interquartile range = 54-68). HM diagnoses included multiple myeloma (n = 10), leukemia (n = 5), lymphoma (n = 4), and myelofibrosis (n = 1). Eight themes emerged from interviews that seemed to influence HM-related pain self-management, including (1) fear of opioid-related harms, (2) opioid side effects and harms to health, (3) fatalism and stoicism, (4) perceived value of opioids for HM-related pain, (5) low perceived susceptibility to opioid-related harms and externalizing blame, (6) preferences for non-opioid pain management approaches, (7) trust in providers and opioid accessibility, and (8) external sources of pain management support and information., Conclusions: This qualitative study demonstrates that fears and stigmatized views of opioids can conflict with marginalized patients' needs to manage debilitating HM-related pain. Negative attitudes towards opioids were shaped by the opioid epidemic and reduced willingness to seek out or use analgesics., Implications for Cancer Survivors: These findings help expose patient-level barriers to optimal HM pain management, revealing attitudes, and knowledge to be targeted by future pain management interventions in HM., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with hematological malignancies (HMs) are more frequently admitted now than in the past to the intensive care unit (ICU) due to more aggressive approaches in primary therapy of HMs and the need for critical care support. Pathophysiological alterations derived from HMs and the different hematological therapies, such as chemotherapy, negatively affect gastrointestinal (GI) function, metabolism, and nutrition status. Further, malnutrition strongly influences outcomes and tolerance of the different hematological therapies. In consequence, these critically ill patients frequently present with malnutrition and pathophysiological alterations that create challenges for the delivery of medical nutrition therapy (MNT) in the ICU. Frequent screening, gauging tolerance, and monitoring nutrition status are mandatory to provide individualized MNT and achieve nutrition objectives. The present review discusses how HM impact GI function and nutrition status, the importance of MNT in patients with HM, and specific considerations for guidance in providing adequate MNT to these patients when admitted to the ICU., (© 2024 The Authors. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Purpose of Review: As society continues to advance in technology, it is important to address how this advancement can impact and enhance patient care. The purpose of this review is to identify patient-centered technology currently available for adult and pediatric patients with and those having survived hematologic malignancies. Given that patients with hematologic malignancies often have to adhere to strenuous medication regimens, coordinate care with many different providers, manage symptoms associated with treatment, and manage late effects associated with survivorship, they would benefit greatly from patient-centered technology aimed at decreasing these burdens., Recent Findings: This review found various available digital interventions for this patient population and focuses on an overview of commercially available smartphone applications, patient portals, and technology for remote monitoring. In summary, many digital interventions exist for use in the medical care of oncology patients. The incorporation of these interventions can allow for more personalized medical care, better organization of treatment plans by caregivers at home, and easy delivery of accurate medical information., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Among adolescents and young adults, hematological malignancies are the most common malignancies. Although the survival rate of hematological malignancies in young patients has been dramatically improved, due to the continuous improvement and development of tumor diagnosis and treatment options, cytotoxic therapies can significantly reduce a patient's reproductive capacity and cause irreversible infertility. The most two established solutions are embryo cryopreservation and oocyte cryopreservation which can be considered in single female. Sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. A comprehensive consultation with reproductive specialists when once diagnosed is a significantly issue which would help those survivors who want to have children. In this article, we review germ cell toxicity, which happens during the treatment of hematological malignancies, and aims to propose safety, efficacy fertility preservation methods in younger patients with hematological malignancies., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Cardio-oncology, a burgeoning subspecialty, addresses the complex interplay between cardiology and oncology, particularly in light of increased cardiovascular (CV) disease mortality in cancer patients. This review provides a comprehensive overview of cardio-oncology with a focus on the therapies used in hematological malignancies. We explore the bidirectional relationship between heart failure and cancer, emphasizing the need for collaborative care. The review discusses risk stratification, highlighting the importance of baseline CV risk assessment and personalized surveillance regimens. Primary and secondary prevention strategies, including pharmacological interventions, are outlined. The review also delves into the cardiotoxicity associated with hematological cancer therapies, focusing on anthracyclines, Bruton kinase inhibitors, BCR-ABL tyrosine kinase inhibitors, CAR-T cell therapy, immune checkpoint inhibitors, multiple myeloma treatments, and hematopoietic stem cell transplantation. We then highlight the high risk of venous and arterial thromboembolisms in cancer patients and the challenges of anticoagulation management in cardio-oncology. Finally, the review touches on the importance of long-term follow-up and appropriate screening in cancer survivors at high risk of CV morbidity and mortality, based on their CV risk profile and the type and dose of cardiotoxic therapies they received such as anthracyclines or high radiation doses., Competing Interests: Both authors received a grant from Boehringer Ingelheim for SGLT2i in cardio-oncology patients., (Thieme. All rights reserved.)

Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors., (© 2024. The Author(s).)

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18 years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates on practical information needed for the management of oral complications of cancer patients. This CPS is focused on the current understanding of controversies that may arise while providing basic oral care in hemato-oncology patients and hematopoietic cell transplantation recipients (HCT). The CPS will summarize and elucidate controversies that have appeared in the literature and professional discussions., Methods: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care., Results: Controversies about the use of chlorhexidine (CHX) oral rinse, mechanical dental plaque removal procedures, the need for toothbrush replacement during phases of low blood cell counts, and the use of lidocaine mouthwash for oral pain were identified and discussed. Consensus about the best standard of care was outlined., Conclusion: The following ratifications are applicable for oral care in hemato-oncology patients and patients undergoing HCT: (1) CHX may reduce the risk of oral infections, although it was not found to reduce the risk of oral mucositis. (2) Toothbrushing and proficient interproximal cleaning should not be discouraged during HCT. (3) Toothbrushes do not need to be replaced daily and are preferred over cleansing swabs. (4) Lidocaine rinse, swish and spit, may be considered to palliate oral mucosal pain if applied in a certain manner., (© 2024. The Author(s).)

Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival ( P = 0.001) and 6.6% increase in treatment-related mortality within 3 y ( P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients., Competing Interests: Competing interests statement:The authors declare no competing interest.

Abstract: Allogeneic blood and marrow transplantation (alloBMT) is increasingly being used in older patients with blood cancer. Aging is associated with an increasing incidence of clonal hematopoiesis (CH). Although the effects of donor CH on alloBMT has been reported, the impact of recipient CH on alloBMT outcomes is unknown. In this retrospective study, alloBMT recipients age 60 and older with lymphoid malignancies were included. Among 97 consecutive patients who received alloBMT between 2017 and 2022, CH was detected in 60 (62%; 95% confidence interval [CI], 51-72). CH was found in 45% (95% CI, 28-64) of patients aged 60 to 64, 64% (95% CI, 44-81) of patients aged 65% to 69%, and 73% (95% CI, 59-87) in those above 70. Pretransplant CH was associated with worse survival after alloBMT: 3-year overall survival (OS) was 78% (95% CI, 65-94) for patients without CH vs 47% (95% CI, 35-63) for those with CH, (unadjusted HR, 3.1; [95% CI, 1.4-6.8; P < .001]). Nonrelapse mortality (NRM) was higher in patients with CH; cumulative incidence of NRM at 1-year was 11% (95% CI, 1-22) vs 35% (95% CI, 23-48), (HR, 3.4; [95% CI, 1.4-8.5], P = .009]). Among CH patients, worse OS and NRM was associated with CH burden and number of mutations. Recipient CH had no effect on relapse. In conclusion, older patients with CH experience worse outcomes after alloBMT, almost exclusively attributable to increased NRM. CH is a strong, independent predictor of outcomes. Novel strategies to ameliorate the adverse impacts of patient CH on transplant outcomes are being evaluated., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers.

Hematopoietic stem cell transplantation (HSCT) is a widely used treatment for malignant hematological diseases; however, some patients inevitably experience relapse. Therefore, for patients who relapse after the first HSCT (HSCT1), a standard treatment regimen must be developed. A second hematopoietic stem cell transplantation (HSCT2) is a possible treatment option. Several studies have analyzed the feasibility of HSCT2. Previous studies have shown that various factors may affect the efficacy of HSCT2, including the hematopoietic cell transplantation comorbidity index, duration of remission after HSCT1, occurrence of chronic graft-versus-host disease, and disease status before HSCT2. However, the selection of donors for HSCT2 does not affect the transplantation efficacy. HSCT2 also presents a risk of relapse, and the prognosis of patients after relapse is poor. Further research on the treatment of patients after relapse is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Zhu and Xiao.)

Abstract: Use of surrogates as primary end points is commonplace in hematology/oncology clinical trials. As opposed to prognostic markers, surrogates are end points that can be measured early and yet can still capture the full effect of treatment, because it would be captured by the true outcome (eg, overall survival). We discuss the level of evidence of the most commonly used end points in hematology and share recommendations on how to apply and evaluate surrogate end points in research and clinical practice. Based on the statistical literature, this clinician-friendly review intends to build a bridge between clinicians and surrogacy specialists., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)