Transfusion Medicine and Hemotherapy最新文献

Introduction: Robotic-assisted surgery is increasingly performed in various surgical disciplines demonstrating improved oncological and functional outcomes compared to conventional surgery.

Objective: Unclear is how robotic-assisted surgery affects perioperative anemia and the need for blood products.

Methods: In this case-control study, 15,009 matched patient pairs undergoing urological, visceral, or thoracic surgery were included. Pairwise comparisons between robotic-assisted surgery, laparoscopic surgery, and open surgery were performed with propensity score matching.

Results: Robotic-assisted surgery compared to open surgery was associated with a risk reduction of allogeneic red blood cell transfusion by RR: 0.32 (95% CI: 0.27-0.37) and a limited reduction of perioperative hemoglobin (perioperative hemoglobin difference of 0.40 g/dL, 95% CI: 0.31-0.49). Robotic-assisted surgery was associated with a shorter length of hospital stay by 4.29 days (95% CI: 3.74-4.84). Compared to laparoscopic surgery, robotic-assisted surgery had no significant effect on red blood cell transfusions (RR: 0.94, 95% CI: 0.75-1.18), perioperative hemoglobin (0.27 g/dL, 95% CI: 0.16-0.38), or length of hospital stay 0.53 days (95% CI: -0.14-1.19).

Conclusions: Robotic-assisted and laparoscopic procedures are associated with reduced blood transfusions compared to open surgery and, thus the advancement of minimally invasive procedures constitutes an important measure to improve patient outcomes.

Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a high relapse rate and still limited therapeutic options. Natural killer (NK) cell-based immunotherapy has the potential to improve outcomes for patients with AML.

Summary: Recent preclinical studies and early-stage clinical trials aim to enhance the intrinsic anti-leukemic properties of NK cells by selectively targeting AML cells with chimeric antigen receptors (CARs). Furthermore, NK and CAR-NK cells can be combined with other therapeutic modalities or engineered further to overcome the immunosuppressive microenvironment, and treatment resistance of AML blasts and leukemia-initiating cells (LIC).

Key messages: In this review, we summarize preclinical studies with cytokine-stimulated or genetically engineered NK cells derived from different cell sources for the treatment of AML and their translation into early-phase clinical trials. We also provide an overview of promising recent developments toward innovative NK cell-based therapies that may be implemented in the near future.

Background: Immunocompromised individuals are at major risk for severe infectious complications. This is particularly relevant in the context of allogeneic hematopoietic stem cell transplantation (allo-HCT) - a treatment modality that has proven curative for a range of malignant and nonmalignant hematological diseases. However, transplant-associated immune suppression leaves patients susceptible to infectious complications from viruses such as cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and BK virus (BKV). While pharmacological agents are available to prevent and/or treat some of these viruses, they can be associated with significant toxicities and are often ineffective. To circumvent these issues, several groups have explored the clinical potential of adoptively transferred virus-specific T cells (VSTs) to prevent/treat virus-associated complications after allo-HCT or solid organ transplantation (SOT) and this review will provide an overview of these endeavors.

Summary: This review will focus on the progress that has been made over the past 30 years in the field of nonengineered VST manufacturing technologies and will summarize the clinical experience with VSTs, primarily in the posttransplant setting.

Key messages: Over the last 3 decades, adoptively transferred VSTs - both HCT donor and third party-derived - have been tested in numerous single and multicenter clinical trials and have unequivocally proven to be safe and associated with clinical activity.

Background: Immunotherapies in general, and cellular immunotherapies, in particular are becoming increasingly integrated into current personalized cancer treatment, though still facing some obstacles in the allogeneic hematopoietic stem cell transplantation (HSCT) setting.

Summary: The concept of isolating immune effector cells, expanding their numbers, enhancing their anticancer capabilities by modifying them without increasing their alloreactive potential is the mainstay of adoptive cellular immunotherapy after allogeneic HSCT. In this context, cytokine-induced killer (CIK) cells, a polyfunctional heterogenous population of conventional T cells, natural killer (NK) cells, and T-NK cells capable of using T cell and NK cell-like cytotoxicity mechanisms against a various cancers, showed minimal alloreactivity in pediatric and adult patients allografted for hematological malignancies. Furthermore, CIK cells have already shown compatibility with chemotherapy, different kinds of immune checkpoint inhibitors, epigenetic drugs, antibody-targeted therapies, and recently with chimeric antigen receptor-engineering techniques.

Key messages: Hence, CIK cell therapy represents a unique platform for adoptive cell immunotherapies, guiding innovative treatment approaches from preclinical research to future clinical trials for cancer patients with yet unmet medical needs. In this context, the allogeneic HSCT setting provides an alternative source for safe and efficient adoptive allogeneic CIK cell strategies against a variety of cancers.

[This corrects the article DOI: 10.1159/000502158.].

Objectives: This study aimed to evaluate the distribution of genotypes and iron metabolism imbalance in transfusion-dependent thalassemia patients.

Methods: Genotype analysis was conducted on 84 thalassemia patients requiring transfusion, and retrospective analysis of iron overload was performed on 48 transfusion-dependent patients.

Results: Among the 84 thalassemia cases requiring transfusion, six mutations of α-thalassemia were identified, including --^SEA, α^CS, -α^3.7, -α^4.2, α^QS, and α^WS. Nine mutations of β-thalassemia were also found, with CD41-42 being the most common. Of the 48 transfusion-dependent patients, 40 (83.3%) had iron overload with serum ferritin (SF) levels above 1,000 ng/mL. The recent SF level was lower than 3 years ago, but the overall ferritin level remains elevated.

Conclusions: β-thalassemia was the predominant type among transfusion-dependent thalassemia patients, with CD41-42/-28, CD41-42/IVS-II-654, and CD17/IVS-II-654 being the most common genotypes. Proper blood transfusion and iron chelation therapy are essential for managing transfusion-dependent thalassemia. While some patients show a reduction in SF levels after 3 years of treatment, there are still individuals who exhibit elevated levels necessitating ongoing management.

Background: Autoimmune hemolytic anemia (AIHA) is a rare disease due to increased destruction of erythrocytes by autoantibodies, with or without complement activation.

Summary: AIHA is usually classified in warm AIHA (wAIHA) and cold agglutinin disease (CAD), based on isotype and thermal amplitude of the autoantibody. The direct antiglobulin test (DAT) or Coombs test is the cornerstone of AIHA diagnosis, as it is positive with anti-IgG in wAIHA, and with anti-C3d/IgM antisera plus high titer cold agglutinins in CAD. Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter. Splenectomy, which is still a good option for young/fit wAIHA, is contraindicated in CAD, and classic immunosuppressants are moving to further lines. Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan). Clinically, AIHAs are highly heterogeneous, from mild/compensated to life-threatening/fulminant, and may be primary or associated with infections, neoplasms, autoimmune diseases, transplants, immunodeficiencies, and drugs. Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging.

Key messages: This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies.

Background: The clinical success of autologous adoptive cell therapy (ACT) is substantial but wide application is challenged by the quality and quantity of the patient's immune cells and the need for personalized manufacturing processes. Induced pluripotent stem cells (iPSCs) can be differentiated into immune effectors and thus provide an alternative, allogeneic cell source for ACT. Here, we compare iPSC-derived immune effectors to their PBMC-derived counterparts and review iPSC-derived ACT products currently under preclinical and clinical development.

Summary: iPSC-derived T cells, NK cells, macrophages, and neutrophils largely mimic their PBMC-derived counterparts in terms of cell-surface marker expression and cytotoxic effector functions. iPSC-derived immune effectors can be engineered with chimeric antigen receptors and other activating receptors to redirect their cytotoxic potential specifically to tumor-associated antigens (TAAs). However, several differences between iPSC- and PBMC-derived immune effectors remain and have inspired additional engineering strategies to enhance the antitumor capacity of iPSC-derived immune effectors.

Key messages: iPSCs can be engineered to facilitate the generation of immune effectors with homogenous specificity for TAAs and enhanced effector functions. TAA-specific and functionally enhanced iPSC-derived T and NK cells are currently undergoing clinical evaluation in phase 1 trials. Engineered iPSC-derived macrophages and neutrophils are in preclinical development.

Introduction: Red blood cells (RBCs) undergo progressive biochemical and morphological changes during storage, collectively called storage lesion. The quality of red cell concentrates (RCCs) is typically assessed by quantifying hemolysis. An assessment of morphological changes, associated with low quality RBCs, could give an additional indication of the safety and efficacy of the concentrates. The current standard for determining morphological changes is a manual, laborious, and subjectively biased microscopic process that limits the number of cells that can be examined. When using alternative methods like flow cells, flow and shear-induced morphologies affecting especially stomatocyte morphologies must be taken into account. We already established an automated flow morphometric RBC analysis system as an alternative to manual microscopic evaluation. The goal of the present work is to obtain a robust, automated, morphology-related signal (lesion index) quantifying RBC storage lesion in a laminar flow channel under conditions similar to stasis that is not affected by shear-induced reversible morphology changes.

Methods: We use a convolutional neural network (CNN) for high throughput classification of RBCs. We analyzed the morphological changes of 5 RCCs over a period of 12 weeks and classified RBC morphologies, including such that are degradation-induced and reversible. We introduce a lesion index to denote the percentage of irreversible spherical morphologies, known to reduce the post-transfusion survival of erythrocytes. We further addressed shear-induced stomatocyte morphologies in laminar flow and whether these affect CNN-based RBC classification.

Results: Our flow morphometry system achieves a high-resolution classification comprising nine morphological classes with an excellent overall accuracy of 92% and F₁ scores between 84% and 97%. We generate strong evidence that the morphological lesion index can predict the hemolysis level in RCCs during storage. The power of this new classification technique allowed it, for the first time, to detect and measure the lateral concentration gradient of stomatocytes in a conventional flow chamber. Importantly, we show that reversible shear rate-induced morphologies, typical for microfluidic systems, bear no influence on the lesion index.

Conclusion: Flow morphometry combined with evaluation by a CNN allows to reliably assess RBC storage lesion and thus concentrate quality. Additionally, this method reduces the need for complex laboratory procedures.