Financial toxicity, coping strategies, and quality of life among Chinese patients with hematologic malignancies: a cross-sectional study.

PURPOSE: Financial toxicity is used to describe the financial hardship experienced by cancer patients. Financial toxicity may cause negative consequences to patients, whereas little is known in Chinese context. This study aimed to explore the level of financial toxicity, coping strategies, and quality of life among Chinese patients with hematologic malignancies. PATIENTS AND METHODS: We conducted a prospective, observational study among 274 Chinese patients with hematologic malignancies from November 2021 to August 2022 in Sun Yat-sen University Cancer Center. Clinical data were extracted from electronic clinical records. Data on financial toxicity, coping strategies, and quality of life were collected using PRO measures. Chi-square or independent t test and multivariate logistic regression were performed to explore the associated factors of financial toxicity and quality of life, respectively. Effects of financial toxicity on coping strategies were examined using Chi-square. RESULTS: The mean age of the participants was 50.2 (± 14.6) years. Male participants accounted for 57.3%. About half of the participants reported high financial toxicity. An average median of ¥200,000 on total medical expenditures since the diagnosis was reported. The average median monthly out-of-pocket health expenditure relating to cancer treatment was ¥20,000 (range ¥632-¥172,500) after reimbursement. Reduce daily living expenses (64.9%), borrowing money (55.7%), and choosing cheaper regimens (19.6%) were the commonly used strategies to cope with financial burden. Financial toxicity was negatively associated with quality of life (ß = 0.071, P = 0.001). CONCLUSIONS: Financial toxicity was not uncommon in patients with hematological malignancies. Reducing daily living expenses, abandoning treatment sessions, and borrowing money were the strategies commonly adopted by participants to defray cancer costs. Additionally, participants with high level of financial toxicity tended to have worse quality of life. Therefore, actions from healthcare providers, policy-makers, and other stakeholders should be taken to help cancer patients mitigate their financial toxicity.

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

[Research progress of CAR-macrophages in malignant hematological diseases].

This article reviews the development history of chimeric antigen receptor macrophage (CAR-M) therapy, discusses its application in malignant hematologic diseases, introduces related clinical trials, analyzes the advantages and challenges faced by CAR-M therapy in clinical application, and looks forward to its future use in the treatment of malignant hematologic diseases.

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38.

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Advances in CAR-NK cell therapy for hematological malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application has introduced new challenges, such as safety concerns, off-target toxicities, and significant costs. Natural killer (NK) cells are crucial components of the innate immune system, capable of eliminating tumor cells without prior exposure to specific antigens or pre-activation. This inherent advantage complements the limitations of T cells, making CAR-NK cell therapy a promising avenue for hematological tumor immunotherapy. In recent years, preclinical and clinical studies have yielded preliminary evidence supporting the safety and efficacy of CAR-NK cell therapy in hematological malignancies, paving the way for future advancements in immunotherapy. This review aims to succinctly discuss the characteristics, significant therapeutic progress, and potential challenges associated with CAR-NK cell therapy.

The health risk of social disadvantage is transplantable into a new host.

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.

[The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation].

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

Universal CAR 2.0 to overcome current limitations in CAR therapy.

Chimeric antigen receptor (CAR) T cell therapy has effectively complemented the treatment of advanced relapsed and refractory hematological cancers. The remarkable achievements of CD19- and BCMA-CAR T therapies have raised high expectations within the fields of hematology and oncology. These groundbreaking successes are propelling a collective aspiration to extend the reach of CAR therapies beyond B-lineage malignancies. Advanced CAR technologies have created a momentum to surmount the limitations of conventional CAR concepts. Most importantly, innovations that enable combinatorial targeting to address target antigen heterogeneity, using versatile adapter CAR concepts in conjunction with recent transformative next-generation CAR design, offer the promise to overcome both the bottleneck associated with CAR manufacturing and patient-individualized treatment regimens. In this comprehensive review, we delineate the fundamental prerequisites, navigate through pivotal challenges, and elucidate strategic approaches, all aimed at paving the way for the future establishment of multitargeted immunotherapies using universal CAR technologies.

[Challenges and strategies for improving efficacy in CAR-T therapy].

CAR-T cell therapy targeting CD19 and BCMA for relapsed or refractory hematopoietic tumors has been adopted in routine practice and has shown dramatic results. However, half of patients who achieve remission with CAR-T therapy eventually relapse, and thus efforts to improve the efficacy of CAR-T therapy are gaining momentum. Notably, studies have described innovative technologies that enable control of cell kinetics after infusion, which is not possible with conventional CAR-T therapies. In this article, we review the challenges of CAR-T cell therapy and the development of new technologies.

Hematologic Malignancies Influence the Accuracy of Prediction of Survival in Patients With Solid Tumor Spinal Metastases Undergoing Surgery.

PURPOSE: There is no consensus on how to identify patients with multiple-level spinal metastases who would benefit from surgery. Previous studies have revealed that patients with hematologic malignancies have a significantly longer median survival time than those with solid tumor spinal metastases. We aimed to compare predictors and survival data between patients with spinal metastases, including hematologic malignancies (all-malignancies group), with only those with nonhematologic malignancies (nonhematologic malignancies group). MATERIALS AND METHODS: This single-center retrospective study included all patients age >18 years who underwent surgery to treat spinal metastases in our department from 2008 to 2018. The patients' baseline characteristics, treatment modalities, and laboratory results were analyzed. Survival was calculated from the date of surgery to the date of confirmed death. Cox regression analysis was used to identify independent predictors of survival. RESULTS: The study cohort comprised 186 patients with a mean age of 57.1 ± 13.4 years, 101 of whom were male and 18 of whom had hematologic malignancies. The median survival time was 201 days in the all-malignancies group and 168 days in the nonhematologic malignancies group. Independent predictors of survival differed between the two groups. Eastern Cooperative Oncology Group status and response to preoperative chemotherapy were identified as independent factors in both groups. However, radiosensitivity and CNS metastases were identified only in the all-malignancies group, and tumor growth potential, albumin status, and number of vertebrae were identified only in the nonhematologic malignancies group. The receiver operating characteristics were comparable in the two groups: 0.75 in the all-malignancies group and 0.77 in the nonhematologic malignancies group. CONCLUSION: Longer survival in patients with hematologic malignancies influences the overall prediction of survival. Tumor-specific prognostic factors may improve the prediction of survival in patients with spinal metastases.

Economic impact of immunoglobulin replacement therapy in secondary immunodeficiency to hematological cancer: a single center observational study.

This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT-including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.

A bibliometric and knowledge-map study on the treatment of hematological malignancies with CAR-T cells from 2012 to 2023.

Recently, CAR-T cell therapy in hematological malignancies has received extensive attention. The objective of this study is to gain a comprehensive understanding of the current research status, development trends, research hotspots, and emerging topics pertaining to CAR-T cells in the treatment of hematological malignancies. Articles pertaining to CAR-T cell therapy for hematological malignancies from the years 2012 to 2023 were obtained and assessed from the Web of Science Core Collection (WoSCC). A bibliometric approach was employed to conduct a scientific, comprehensive, and objective quantitative analysis, as well as a visual analysis, of this particular research domain. A comprehensive analysis was conducted on a corpus of 3643 articles, which were collaboratively authored by 72 countries and various research institutions. CAR-T cell research in treating hematological malignancies shows an increasing trend each year. Notably, the study identified the countries and institutions displaying the highest level of activity, the journals with the most citations and output, as well as the authors who garnered the highest frequency of citations and co-citations. Furthermore, the analysis successfully identified the research hotspots and highlighted six emerging topics within this domain. This study conducted a comprehensive exploration and analysis of the research status, development trends, research hotspots, and emerging topics about CAR-T cells in the treatment of hematological malignancies from 2012 to 2023. The findings of this study will serve as a valuable reference and guide for researchers seeking to delve deeper into this field and determine the future direction of their research.

PET/CT in the Evaluation of CAR-T Cell Immunotherapy in Hematological Malignancies.

Chimeric antigen receptor (CAR)-T cell-based immunotherapy has emerged as a path-breaking strategy for certain hematological malignancies. Assessment of the response to CAR-T therapy using quantitative imaging techniques such as positron emission tomography/computed tomography (PET/CT) has been broadly investigated. However, the definitive role of PET/CT in CAR-T therapy remains to be established. [18F]FDG PET/CT has demonstrated high sensitivity and specificity for differentiating patients with a partial and complete response after CAR-T therapy in lymphoma. The early therapeutic response and immune-related adverse effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome can also be detected on [18F]FDG PET images. In otherwise asymptomatic lymphoma patients with partial response following CAR-T therapy, the only positive findings could be abnormal PET/CT results. In multiple myeloma, a negative [18F]FDG PET/CT after receiving B-cell maturation antigen-directed CAR-T therapy has been associated with a favorable prognosis. In leukemia, [18F]FDG PET/CT can detect extramedullary metastases and treatment responses after therapy. Hence, PET/CT is a valuable imaging tool for patients undergoing CAR-T therapy for pretreatment evaluation, monitoring treatment response, assessing safety, and guiding therapeutic strategies. Developing guidelines with standardized cutoff values for various PET parameters and tumor cell-specific tracers may improve the efficacy and safety of CAR-T therapy.

Health professionals' perceptions of prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults.

PURPOSE: Haematologic malignancies for the most part are diseases of the elderly. Haematopoietic stem cell transplantation (HSCT) remains the only potentially curative strategy for many patients but carries substantial morbidity and mortality risks, particularly in frail or co-morbid patients. Pre-transplant optimisation of key targets through prehabilitation may have significant clinical impact. METHODS: We utilised qualitative methodology (semi-structured interviews) to gain insights and understanding of the perceptions of medical, nursing and allied health professionals towards prehabilitation before haematopoietic cell transplantation to optimise candidacy in older adults. Thematic analysis was performed using a qualitative descriptive approach completed in duplicate by two researchers. RESULTS: Between August and October 2023, eleven health professionals participated from four large cancer centres across the island of Ireland (n = 3 consultant haematologists, n = 7 specialist haematology nurses and n = 1 senior haematology physiotherapist). Four major themes were identified. The themes comprehensive biopsychosocial care and increasing demand for transplant in older patients highlight the unique challenges impacting older adults who receive HSCT. The multimodality pathways of care theme highlights the heterogeneity of treatment pathways across different clinical sites and disease types. This has implications for the prehabilitation: logistics and benefits theme, which indicated strong support for prehabilitation but emphasised that implementation must consider national reach and context. CONCLUSIONS: There is broad national multidisciplinary interest in the development of prehabilitation programmes for patients being considered for transplant. Our results will inform the development of services in this area in consideration of national reach, malignancy-specific pathways and the unique factors associated with older age.

Advances in CAR-T-cell therapy in T-cell malignancies.

Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress of preclinical and clinical studies in this area. We present an analysis of clinical trials of CAR-T-cell therapies for the treatment of T-cell malignancies grouped by target antigen classification. Moreover, this review focuses on the major challenges encountered by CAR-T-cell therapies, including the nonspecific killing due to T-cell target antigen sharing and contamination with cell products during preparation. This review discusses strategies to overcome these challenges, presenting novel therapeutic approaches that could enhance the efficacy and applicability of CAR-T-cell therapy in the treatment of T-cell malignancies. These ideas and strategies provide important information for future studies to promote the further development and application of CAR-T-cell therapy in this field.

Prospects and Potential for Chimerism Analysis after Allogeneic Hematopoietic Stem Cell Transplantation.

Chimerism analysis after allogeneic hematopoietic stem cell transplantation serves to confirm engraftment, indicate relapse of hematologic malignancy, and attribute graft failure to either immune rejection or poor graft function. Short tandem repeat PCR (STR-PCR) is the prevailing method, followed by quantitative real-time PCR (qPCR), with detection limits of 1-5% and 0.1%, respectively. Chimerism assays using digital PCR or next-generation sequencing, both of which are more sensitive than STR-PCR, are increasingly used. Stable mixed chimerism is usually not associated with poor outcomes in non-malignant diseases, but recipient chimerism may foretell relapse of hematologic malignancies, so higher detection sensitivity may be beneficial in such cases. Thus, the need for and the type of intervention, e.g., immunosuppression regimen, donor lymphocyte infusion, and/or salvage second transplantation, should be guided by donor chimerism in the context of the feature and/or residual malignant cells of the disease to be treated.

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial.

BACKGROUND: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. METHODS: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. RESULTS: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72-98) and 88% (95% CI: 67-96); ≥ CR2 were 81% (95% CI: 61-92) and 68% (95% CI: 47-82) and refractory disease were 32% (95% CI: 11-54) and 20% (95% CI: 6-40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64-87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/µL and 140/µL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). CONCLUSION: The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).

Recent Advances in CAR-T Therapy.

Chimeric antigen receptor T cell therapy is used to treat hematological malignancies which are refractory to standard therapy. It is a form of immunotherapy in which a patient's T cells are programmed to act against tumor cells. We discuss the process of manufacturing CAR-T cells, the common side effects of therapy, and the recent emerging risk of T-cell malignancies after treatment.

Advances in research on factors affecting chimeric antigen receptor T-cell efficacy.

Chimeric antigen receptor T-cell (CAR-T) therapy is becoming an effective technique for the treatment of patients with relapsed/refractory hematologic malignancies. After analyzing patients with tumor progression and sustained remission after CAR-T cell therapy, many factors were found to be associated with the efficacy of CAR-T therapy. This paper reviews the factors affecting the effect of CAR-T such as tumor characteristics, tumor microenvironment and immune function of patients, CAR-T cell structure, construction method and in vivo expansion values, lymphodepletion chemotherapy, and previous treatment, and provides a preliminary outlook on the corresponding therapeutic strategies.