Hemoglobin Binding to the Red Blood Cell (RBC) Membrane Is Associated with Decreased Cell Deformability.

The deformability of red blood cells (RBCs), expressing their ability to change their shape as a function of flow-induced shear stress, allows them to optimize oxygen delivery to the tissues and minimize their resistance to flow, especially in microcirculation. During physiological aging and blood storage, or under external stimulations, RBCs undergo metabolic and structural alterations, one of which is hemoglobin (Hb) redistribution between the cytosol and the membrane. Consequently, part of the Hb may attach to the cell membrane, and although this process is reversible, the increase in membrane-bound Hb (MBHb) can affect the cell's mechanical properties and deformability in particular.

Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins.

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias.

Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies.

Background: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells.

Methods: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102).

Hemolytic Activity of Nanoparticles as a Marker of Their Hemocompatibility.

The potential use of nanomaterials in medicine offers opportunities for novel therapeutic approaches to treating complex disorders. For that reason, a new branch of science, named nanotoxicology, which aims to study the dangerous effects of nanomaterials on human health and on the environment, has recently emerged. However, the toxicity and risk associated with nanomaterials are unclear or not completely understood.

A case series of eosinophilic myocarditis: different faces of the same coin.

Background: Eosinophilic myocarditis (EM) is a rare form of myocarditis with various aetiologies and dire consequences if not diagnosed and treated expeditiously.

Case Summary: We report three cases of EM at different stages of the disease with differing clinical manifestations. We highlight the diagnostic workup including the role of multimodality imaging and endomyocardial biopsy (EMB), and the treatment strategies.

Re-induction versus salvage for D14-resiudal acute myeloid leukemia: A retrospective multi-center study.

Remission assessment in acute myeloid leukemia has evolved over the recent years with the advent of molecular and flow-based minimal residual disease determination. Nonetheless, early time point such as day 5 and day 14 (D14), still have prognostic and therapeutic implications. D14 refractory disease is regarded as a poor prognostic factor, however the therapeutic intervention is still under debate, with evidence suggesting a successful re-induction might offer similar long-term outcome as D14 aplasia.

Rituximab, methotrexate, procarbazine and lomustine (R-MPL) for the treatment of primary Central nervous system lymphoma.

The optimal high-dose methotrexate (HDMTX)-based combination therapy for primary central nervous system lymphoma is unknown. We report our experience with rituximab, HDMTX, procarbazine and lomustine (R-MPL) given as first-line treatment in our center. Fifty-two patients between 2006 and 2019 were included.

Determination of red blood cell adhesion to vascular endothelial cells: A critical role for blood plasma.

Red blood cell (RBC) adhesion to vascular endothelial cells (EC) is considered a potent effector of circulatory disorders, and its enhancement is implicated in the pathophysiology of numerous conditions, mainly hemoglobinopathies. The actual RBC/EC interaction is determined by both cellular and plasmatic factors, and the differentiation between them is essential for understanding its physiological implications. Yet, RBC/EC adhesion has been studied predominantly in protein-free media.

Deformability of Stored Red Blood Cells.

Red blood cells (RBCs) deformability refers to the cells' ability to adapt their shape to the dynamically changing flow conditions so as to minimize their resistance to flow. The high red cell deformability enables it to pass through small blood vessels and significantly determines erythrocyte survival. Under normal physiological states, the RBCs are attuned to allow for adequate blood flow.

Do We Store Packed Red Blood Cells under "Quasi-Diabetic" Conditions?

Red blood cell (RBC) transfusion is one of the most common therapeutic procedures in modern medicine. Although frequently lifesaving, it often has deleterious side effects. RBC quality is one of the critical factors for transfusion efficacy and safety.

Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome.

Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome.

Venetoclax combinations induce high response rates in newly diagnosed acute myeloid leukemia patients ineligible for intensive chemotherapy in routine practice.

Combinations of the BCL-2 inhibitor, venetoclax, with either hypomethylating agents (HMA) or low dose cytarabine (LDAC), have shown promising results in clinical trials of AML patients unfit for intensive therapy. We report on the efficacy and safety of venetoclax combinations in AML patients treated outside of clinical trials. Complete remission (CR) + CR with incomplete count recovery (CRi) were achieved in 61% of patients, with similar CR+CRi rates in with secondary AML, and in patients who were previously treated with HMA (61% and 43%, respectively).

Diagnostic and Management Difficulty of Bleeding Aorto-Duodenal Fistula Associated with Hodgkin's Lymphoma.

Primary aorto-enteric fistula (AEF) resulting from abdominal malignancy is a rare and often fatal complication. The few reports to date are mostly secondary to solid tumors. We present a case of a patient with refractory Hodgkin's lymphoma who developed life-threatening AEF.

Unit-to-unit variability in the deformability of red blood cells.

Background: In blood banking practice, the storage duration is used as the primary criterion for inventory management, and usually, the packed red blood cells (PRBC) units are supplied primarily according to first-in-first-out (FIFO) principle. However, the actual functionality of individual PRBC units is mostly ignored. One of the main features of the RBCs not accounted for under this approach is the deformability of the red cells, i.

Venetoclax is safe and efficacious in relapsed/refractory AML.

Data from 11 Israeli centers, where venetoclax was used for relapsed/refractory AML after intensive chemotherapy, were retrospectively collected. During 2016-2019, forty patients were identified. Median age was 67 years (21-82), 60% males, median of 2(1-4) prior lines of treatment and 42% relapsed after allogeneic transplant.

Non-oxidative band-3 clustering agents cause the externalization of phosphatidylserine on erythrocyte surfaces by a calcium-independent mechanism.

Aging of red blood cells (RBCs) is associated with alteration in a wide range of RBC features, occurring each on its own timescale. A number of these changes are interrelated and initiate a cascade of biochemical and structural transformations, including band-3 clustering and phosphatidylserine (PS) externalization. Using specific band-3 clustering agents (acridine orange (AO) and ZnCl), we examined whether treatment of RBCs with these agents may affects PS externalization and whether this process is Ca-dependent.

Preparation of packed red blood cell units in the blood bank: Alteration in red blood cell deformability.

Background: Donated blood is stored in the blood bank as packed red blood cell units. In the process of packed cells preparation, the red blood cells (RBCs) are subjectedto high level of shear stress, which can induce alterations in their properties. In the present study, we examined the effect of packed RBCs preparation (which included leuko-filtration) on red cell deformability.

Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia.

Tremendous progress in the therapy of pediatric acute lymphoblastic leukemia (ALL) has been achieved through combination cytotoxic chemotherapy, leading to high cure rates, at the cost of significant life-threatening toxicity. The bispecific T-cell engager blinatumomab, recently approved for relapsed/refractory ALL, has a unique nonmyelotoxic toxicity profile. As blinatumomab causes B-cell depletion, the safety of its use during severe chemotherapy-induced toxicity is unclear.

Romidepsin-Bendamustine Combination for Relapsed/Refractory T Cell Lymphoma.

Background: The treatment of relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL) is limited to a few agents. Romidepsin, a histone deacetylase inhibitor, was approved for PTCL treatment as a single agent in the R/R setting, yet with partial efficacy. Several attempts to combine romidepsin with other chemotherapy regimens have been reported, however, with significant toxicity.

A Bortezomib-Based Protocol Induces a High Rate of Complete Remission with Minor Toxicity in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.

The treatment of relapsed/refractory acute lymphoblastic leukemia (RR-ALL) presents a true clinical challenge. In 2012, a protocol combining bortezomib, dexamethasone, asparaginase, doxorubicin, and vincristine administered to children with RR-ALL was published with encouraging results. Over the past 5 years, we have implemented this protocol in the adult RR-ALL population (> 18 years) and addressed its feasibility in terms of remission rate and toxicity.

Retrospective study to investigate fresh frozen plasma and packed cell ratios when administered for women with postpartum hemorrhage, before and after introduction of a massive transfusion protocol.

Background: Administration of packed red blood cells (PRBC) and fresh frozen plasma (FFP) to women with postpartum hemorrhage (PPH) before and after introduction of a massive transfusion protocol.

Methods: The retrospective PPH study cohort of two tertiary centers was identified using blood bank records, verified by patient electronic medical records. We identified women transfused with ≥3 units PRBC in a short time period within 24 hours of delivery.

Is It Possible to Reverse the Storage-Induced Lesion of Red Blood Cells?

Cold-storage of packed red blood cells (PRBCs) in the blood bank is reportedly associated with alteration in a wide range of RBC features, which change cell storage each on its own timescale. Thus, some of the changes take place at an early stage of storage (during the first 7 days), while others occur later. We still do not have a clear understanding what happens to the damaged PRBC following their transfusion.

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis.

Objective: Daratumumab is a promising new antimyeloma agent. We report a single center "real-world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab.

Methods: Forty-one patients were included: 7 second-line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL.

Alopecia Areata as a Manifestation of Systemic Lymphoma: Report of Two Cases.

Alopecia areata is a common autoimmune disorder leading to hair loss. It usually affects individuals under the age of 40, and first appearance in older subjects is considered uncommon. Here, we report 2 cases of rapidly progressing alopecia areata, which appeared for the first time in adults.