Adoptive transfer of neoantigen-specific T-cell therapy is feasible in older patients with higher-risk myelodysplastic syndrome.

Background: Myelodysplastic syndromes (MDS) represent the most common type of acquired bone marrow failure in adults and is characterized by ineffective maturation of myeloid precursor cells and peripheral cytopenias associated with higher rates of infection, bleeding and transfusion dependence. In higher-risk patients with MDS who relapse or do not respond after standard hypomethylating agent (HMA) therapy, the 2-year survival rate is 15%.

Methods: Here the authors report the feasibility and safety of a novel experimental T-cell therapy called personalized adoptive cell therapy, which selects, immunizes and expands T cells against MDS-specific mutations and is targeted to patient-specific tumor cell neoantigens.

In vitro induction of neoantigen-specific T cells in myelodysplastic syndrome, a disease with low mutational burden.

Therapies that utilize immune checkpoint inhibition work by leveraging mutation-derived neoantigens and have shown greater clinical efficacy in tumors with higher mutational burden. Whether tumors with a low mutational burden are susceptible to neoantigen-targeted therapy has not been fully addressed. To examine the feasibility of neoantigen-specific adoptive T-cell therapy, the authors studied the T-cell response against somatic variants in five patients with myelodysplastic syndrome (MDS), a malignancy with a very low tumor mutational burden.

Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists.

This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was analyzed.

A mild acute hemolytic transfusion reaction in a patient with alloanti-Ge3: a case report and review of the literature.

Background: The clinical significance of the Gerbich antibodies has been described as variable and there are no well-documented reports of hemolytic transfusion reactions (HTRs).

Case Report: We present the case of a woman with a long history of documented anti-Ge3 alloantibody who received multiple units of Ge+ red blood cells (RBCs) uneventfully. During the first admission to our hospital she was transfused 8 units of Ge+ RBCs and had a negative monocyte monolayer assay (MMA) before receiving the units.

Study to determine the clinical significance of HEmolysis During Orbital AtheRectomy (CLEAR study).

Purpose: To evaluate the incidence of clinically evident hemolysis associated with orbital atherectomy used to treat severe peripheral artery disease.

Methods: The observational CLEAR study enrolled 31 subjects (16 men; mean age 71 ± 10 years, range 44-92) with claudication (58.1%) or critical limb ischemia (38.

Toxicity-evaluation designs for phase I/II cancer immunotherapy trials.

Objectives: To facilitate more efficient Phase I/II cancer immunotherapy trials by incorporating statistically rigorous safety analysis.

Setting: The standard Phase I oncology trial is designed to find the maximum tolerated dose (MTD) in a setting where serious drug-related toxicity is expected. However, many newer agents hope to show the efficacy without increasing the background rate of adverse events.

Autologous hematopoietic stem cell transplantation as an intensive consolidation therapy for adult patients in remission from acute myelogenous leukemia.

Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myelogenous leukemia (AML). However, its optimal role in treatment for adults in remission has not been clearly established. We performed a retrospective analysis on 45 patients aged 21 to 73 years (median 51 years) with de novo AML who underwent APBSCT stratified by age, complete remission status, and cytogenetic risk.

Liquid storage of marrow stromal cells.

Background: Marrow stromal cells (MSCs) for clinical trials are inevitably stored before administration, but little is known about the effects of storage on MSCs. The effects of short-term liquid storage on the in vitro function of MSCs intended for a clinical trial were studied.

Study Design And Methods: Early-passage human MSCs were suspended in 0.

Collection and preservation of cord blood for personal use.

Unrelated-donor umbilical cord blood (CB) is a useful alternative hematopoietic stem cell source for patients without suitably matched and readily available related or unrelated stem cell donors. Expectant parents today may have the option of either donating the CB to a public CB bank or keeping and storing the CB in a private bank for potential use in the future. The alternatives are often referred to as public banking and private banking.

Generation of T-cell lines to autologous acute myeloid leukemia cells by competitive limiting dilution culture of acute myeloid leukemia mononuclear cells.

Objective: To develop a novel method of generating multiple autologous acute myeloid leukemia (AML) reactive T-cell lines as a step toward adoptive immunotherapy for AML.

Materials And Methods: AML peripheral blood mononuclear cells (MNC), including >90% AML blasts and 1% to 3% T cells, were seeded in limiting dilution culture in which AML blasts were induced to undergo dendritic cell (DC) differentiation. T cells were primed and activated with the addition of a cytokine combination.

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide, sequential granulocyte-macrophage-colony-stimulating factor and granulocyte-colony-stimulating factor, and scheduled commencement of leukapheresis in 225 patients undergoing autologous transplantation.

Background: Interpatient variability in the kinetics of peripheral blood progenitor cell (PBPC) mobilization is commonly seen with conventional chemotherapy-based mobilization regimens. This necessitates the availability of leukapheresis (LP) facilities 7 days a week.

Study Design And Methods: The efficacy of an approach where LP was invariably commenced on Day 11 after intermediate-dose cyclophosphamide followed by sequential administration of granulocyte-macrophage-colony-stimulating factor (CSF) and granulocyte-CSF (Cy/GM/G) was retrospectively analyzed in 225 consecutive, unselected patients undergoing autologous hematopoietic stem cell transplantation for all diagnoses other than acute leukemia at our center.

Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank.

Background: Umbilical cord blood is a useful stem cell source for some patients. The American Red Cross Cord Blood Program was established as a national network of cord blood banks. Nine thousand cord blood units were cryopreserved for transplant use.

Dexamethasone facilitates erythropoiesis in murine embryonic stem cells differentiating into hematopoietic cells in vitro.

Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process.

Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older.

We assessed remission rates and toxicity in 24 consecutive elderly (age>or=60) patients with untreated Acute myeloid leukemia (AML) who received the anthracycline-free combination of fludarabine, cytosine arabinoside and G-CSF (FLAG) as initial induction chemotherapy at our center. CR was achieved following one cycle of FLAG in 14 patients (58%). Another four patients cleared blasts from their bone marrow by day 30 without complete platelet recovery.

Comparison of cytomegalovirus polymerase chain reaction and serology for screening umbilical cord blood components.

Background: Recipients of umbilical cord blood (UCB) transplants are susceptible to opportunistic infections, including cytomegalovirus (CMV). To prevent CMV transmission from UCB donors, most laboratories perform serology on corresponding maternal samples and quarantine units when the mother has immunoglobulin M (IgM) anti-CMV.

Study Design And Methods: UCB units and associated samples (UCB plasma and red cell pellet; maternal whole blood and serum) from two cord blood banks were tested with two validated CMV polymerase chain reaction assays (UL54 and UL93 targets).

Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks.

Banked, unrelated, partially HLA-matched, umbilical cord blood is an alternative stem cell source for patients in need of transplantation therapy who lack traditionally matched donors. A presumed advantage of cord blood is the ability to increase recruitment of donors of minority ethnic backgrounds. The American Red Cross Cord Blood Program was established in 1999 with 6 banks and 10 collection sites throughout the country.

Retention of cellular properties of PBPCs following liquid storage and cryopreservation.

Background: G-CSF-mobilized PBPCs are routinely cryopreserved within 24 hours of collection. The ability to hold PBPCs for extended time would offer increased flexibility for patients and hospitals. Retention of PBPC properties following overnight shipping, extended liquid storage at 1 to 6 degrees C, and cryopreservation was evaluated.

In utero or ex utero cord blood collection: which is better?

Background: The relative nucleated cell count of umbilical cord blood (CB) correlates with improved engraftment and survival. This study compares two collection methods to assess CB content, including cell numbers.

Study Design And Methods: The Massachusetts CB bank used trained obstetricians and midwives to collect CB in utero before the delivery of the placenta.

Mobilization of allogeneic peripheral blood progenitor cells.

It is possible to reliably obtain sufficient PBSC from most normal donors to perform allogeneic transplantation. The mobilization regimen, usually administration of a single daily dose of G-CSF at 7.5 to 10 micrograms/kg subcutaneously for 4 to 6 days, is tolerable with acceptable side effects.

Signs and symptoms associated with the transfusion of WBC-reduced RBCs and non-WBC-reduced RBCs in patients with anemia and HIV infection: results from the Viral Activation Transfusion Study.

Background: RBC transfusion is associated with fever and other reactions in some patients. The Viral Activation Transfusion Study randomly assigned patients to receive either unmodified or WBC-reduced RBCs and thus offered an opportunity to assess the effect of WBC-reduced RBCs on the incidence of transfusion reactions prospectively.

Study Design And Methods: This prospective, randomized, double-blind, multicenter study compared prestorage WBC-reduced RBCs to unmodified RBCs in HIV-infected, CMV-seropositive, and transfusion-naive persons who required transfusions for anemia.