A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy.

Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT.

Background: Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective treatment for multiple sclerosis (MS). The impact of previous long-lasting disease-modifying treatments (DMT) for safety and efficacy of AHSCT is unknown.

Objective: To explore whether previous DMTs with long-lasting effects on the immune system (anti-CD20 therapy, alemtuzumab and cladribine) affect treatment-related complications, long-term outcome and risk of new MS disease activity in patients treated with AHSCT.

Peripheral Blood Stem Cell Mobilization in Healthy Donors by Granulocyte Colony-Stimulating Factor Causes Preferential Mobilization of Lymphocyte Subsets.

Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity.

Study Design And Methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors.

The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis.

Background: Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation.

Methods: Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis.

Results: Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment.

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors.

Introduction: Peripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before.

Objectives: This study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults.

Immunomodulation Induced by Stem Cell Mobilization and Harvesting in Healthy Donors: Increased Systemic Osteopontin Levels after Treatment with Granulocyte Colony-Stimulating Factor.

Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. The frequency of severe graft versus host disease is similar for patients receiving peripheral blood and bone marrow allografts, even though the blood grafts contain more T cells, indicating mobilization-related immunoregulatory effects. The regulatory phosphoprotein osteopontin was quantified in plasma samples from healthy donors before G-CSF treatment, after four days of treatment immediately before and after leukapheresis, and 18-24 h after apheresis.

The pretransplantation serum cytokine profile in allogeneic stem cell recipients differs from healthy individuals, and various profiles are associated with different risks of posttransplantation complications.

Cytokines play a key role in regulation of normal and malignant hematopoiesis, angiogenesis, and inflammation. Serum levels of several cytokines are altered in patients with hematologic malignancies, and pretransplant cytokine levels seem to have a prognostic impact in patients treated with allogeneic stem cell transplantation. However, the cytokine system constitutes an interacting functional network, and it may therefore be more relevant to look at serum cytokine profiles rather than the serum levels of single cytokines in allotransplanted patients.

Future perspectives: should Th17 cells be considered as a possible therapeutic target in acute myeloid leukemia patients receiving allogeneic stem cell transplantation?

Th17 cells seem to promote proinflammatory effects, and their development seems to depend on intracellular signaling initiated by IL1β, supported by IL6 and IL23 and mediated by STAT3 and RORC2. Even though primary human AML cells may affect Th17 development through their constitutive cytokine release, the levels of circulating Th17 cells in older patients with untreated AML do not differ from healthy controls and show only minor variations during and following conventional intensive chemotherapy. IL17-A is the signature cytokine of Th17 cells, but in vitro studies have failed to demonstrate a direct antileukemic effect of IL17 on primary human AML cells for most patient samples.

The chemokine system in allogeneic stem-cell transplantation: a possible therapeutic target?

Further improvements in allogeneic stem-cell transplantation will probably depend on a better balance between immunosuppression to control graft-versus-host disease and immunological reconstitution sufficient to ensure engraftment, reduction of infection-related mortality and maintenance of post-transplant antileukemic immune reactivity. The chemokine network is an important part of the immune system, and, in addition, CXCL12/CXCR4 seem to be essential for granulocyte colony-stimulating factor-induced stem-cell mobilization. Partial ex vivo graft T-cell depletion based on the expression of specific chemokine receptors involved in T-cell recruitment to graft-versus-host disease target organs may also become a future therapeutic strategy; an alternative approach could be pharmacological inhibition (single-receptor inhibitors or dual-receptor inhibitors) in vivo of specific chemokine receptors involved in this T-cell recruitment.

Is there a scientific basis for a recommended standardization of collection and cryopreservation of peripheral blood stem cell grafts?

High-dose chemotherapy followed by autologous stem cell transplantation has been used extensively during the last two decades in the treatment of hematologic malignancies. The vast majority of recent transplantations have been performed using mobilized peripheral blood stem cells, because they have become the preferred source of hematopoietic cells rather than bone marrow stem cells. The mobilization is achieved by growth factors, eventually combined with chemotherapy, and the cells are then harvested and cryopreserved until reinfusion.

Self-treatment of an ABO-incompatible blood transfusion.

Unfortunately, transfusion errors continue to pose a major clinical problem. In practice there is a remarkable lack of understanding of the reasons behind transfusion medicine, a worrying disregard for protocol and an offhand attitude to bedside checking. Clearly transfusion medicine education, as often said, must be more extensively incorporated into the core curriculum of medical, nursing and laboratory staff.

Evaluation of the persistence and characteristics of indeterminate reactivity against hepatitis C virus in blood donors.

Background: A substantial number of individuals are excluded from blood donation due to indeterminate results in screening tests for hepatitis C virus antibody (anti-HCV). Disclosure of the characteristics of the indeterminate serologic pattern could optimize the testing and the management and care of blood donors.

Study Design And Methods: Ninety-two former blood donors deferred from blood donation due to consistent reactivity in anti-HCV enzyme immunoassay and indeterminate HCV recombinant immunoblot assay (RIBA) results were retested for anti-HCV to examine the extent of disappearance of reactivity.

[Blood transfusion and pretransfusion testing in patients with warm autoimmune haemolytic anaemia].

Background: In warm autoimmune haemolytic anaemia, patients have red cell autoantibodies that complicate the serological compatibility testing before transfusion. Different autoadsorption techniques are utilised for more extensive pretransfusion testing. We reviewed the literature on blood transfusion in these patients.