An Unusual Case of Delayed Hemolytic Transfusion Reaction With Hyperhemolysis Syndrome Due to Anti-Jk and Anti-Fy Alloantibodies.

Delayed hemolytic transfusion reaction (DHTR) is a complication appearing a few days to weeks due to alloimmunization following packed red blood cells (RBCs) transfusion, a pregnancy, or transplantation. Hyperhemolysis syndrome (HS) is a severe form of DHTR defined by a drop of hemoglobin to a level lower than before the transfusion, reflecting a destruction of the patient's own RBCs not presenting the targeted antigen as well as the transfused RBCs. Usually seen in sickle cell disease (SCD) patients, HS remains very rare in patients without a hematologic disorder.

Incidence of Post-Operative Complications and Factors Influencing Their Occurrence in Patients with Sickle Cell Disease in a Low-Income Country: A Case Study of Cameroon.

This study aimed to analyse post-operative complications and possible factors influencing their occurrence in the management of patients with sickle cell disease in a low-income country. We prospectively collected data regarding the management of patients with sickle cell disease requiring anesthesia for surgery in 11 Cameroonian hospitals from 1 May 2019 to 30 April 2021. The data were analysed using descriptive statistics and a binary logistic regression was used to determine the dependence between the variables.

Updated recommendations on the use of ruxolitinib for the treatment of myelofibrosis.

Objectives: Myelofibrosis is a rare bone marrow disorder associated with a high symptom burden, poor prognosis, and shortened survival. While allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis, the only approved and reimbursed pharmacotherapy for non-HSCT candidates in Belgium is ruxolitinib.

Methods: These updated recommendations are based on a consensus reached during two meetings and provide guidance for ruxolitinib administration in myelofibrosis patients considering the particularities of Belgian reimbursement criteria.

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry.

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label.

Interruption or Discontinuation of Tyrosine Kinase Inhibitor Treatment in Chronic Myeloid Leukaemia: A Retrospective Cohort Study (SPARKLE) in Belgium.

Objectives: To assess interruptions/discontinuations of tyrosine kinase inhibitor (TKI) treatment in Belgian patients with chronic myeloid leukaemia (CML).

Methods: This retrospective study included patients with TKI interruptions/discontinuations of ≥4 continuous weeks (no clinical trial context) between May 2013 and May 2016. Data collection took place between October 2016 and February 2017.

Identification of chronic myeloid leukemia patients treated with imatinib who are potentially eligible for treatment discontinuation by assessing real-life molecular responses on the international scale in a EUTOS-certified lab.

A retrospective study was performed to describe molecular responses (MR) on the international scale (IS) in patients with chronic myeloid leukemia (CML) treated with imatinib in routine clinical practice in Belgium and to identify patients potentially eligible for treatment discontinuation. The analysis included 116 patients with CML in chronic phase at treatment centers sending blood samples for molecular follow-up to a single EUTOS-certified laboratory. IS MR from the last patient visit between October 2014 and April 2015 were retrospectively collected.

Disease and treatment characteristics of polycythemia vera patients in Belgium: Results from a scientific survey.

Objective: The current survey aimed to gather predefined disease parameters and treatment strategies to characterize the polycythemia vera (PV) patient population in Belgium.

Methods: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analyzed descriptively and quantitatively.

Results: Data from 343 PV patients were collected.

Recommendations on the use of ruxolitinib for the treatment of myelofibrosis.

Objectives: Myelofibrosis (MF) is a severe disease, with decreased life expectancy and heavy symptom burden. Ruxolitinib is the only approved pharmacotherapy for the treatment of MF patients. In Belgium, ruxolitinib is only reimbursed for MF patients with splenomegaly for whom the disease is categorized as intermediate-2 or high risk.

Targeted Treatment Options in Mastocytosis.

Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN).

Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment.

Objective: To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT).

Method: The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database.

Adaptation of Trypanosoma rhodesiense to hypohaptoglobinaemic serum requires transcription of the APOL1 resistance gene in a RNA polymerase I locus.

Human apolipoprotein L1 (APOL1) kills African trypanosomes except Trypanosoma rhodesiense and Trypanosoma gambiense, the parasites causing sleeping sickness. APOL1 uptake into trypanosomes is favoured by its association with the haptoglobin-related protein-haemoglobin complex, which binds to the parasite surface receptor for haptoglobin-haemoglobin. As haptoglobin-haemoglobin can saturate the receptor, APOL1 uptake is increased in haptoglobin-poor (hypohaptoglobinaemic) serum (HyHS).

Spectral domain optical coherence tomography findings in early deferoxamine maculopathy: report of two cases.

Purpose: To describe spectral domain optical coherence tomography features in two cases of early deferoxamine induced retinal toxicity.

Methods: Two patients complained of sudden bilateral visual loss and dyschromatopsia. Both suffered from acute myelocytic leukemia with severe aplastic anemia and were treated with intravenous deferoxamine for 1 month.

The cholinergic anti-inflammatory pathway delays TLR-induced skin allograft rejection in mice: cholinergic pathway modulates alloreactivity.

Activation of innate immunity through Toll-like receptors (TLR) can abrogate transplantation tolerance by revealing hidden T cell alloreactivity. Separately, the cholinergic anti-inflammatory pathway has the capacity to dampen macrophage activation and cytokine release during endotoxemia and ischemia reperfusion injury. However, the relevance of the α7 nicotinic acetylcholine receptor (α7nAChR)-dependent anti-inflammatory pathway in the process of allograft rejection or maintenance of tolerance remains unknown.

Critical role of regulatory T cells in Th17-mediated minor antigen-disparate rejection.

Th17-mediated immune responses have been recently identified as novel pathogenic mechanisms in a variety of conditions; however, their importance in allograft rejection processes is still debated. In this paper, we searched for MHC or minor Ag disparate models of skin graft rejection in which Th17 immune responses might be involved. We found that T cell-derived IL-17 is critical for spontaneous rejection of minor but not major Ag-mismatched skin grafts.

Interleukin 17-producing T helper cells in alloimmunity.

Interleukin (IL) 17 is a proinflammatory cytokine already known to play a defense role against microbes and a pathogenic role in a number of autoimmune diseases. Although IL-17 can be produced by a variety of cells including neutrophils, CD8+, NK, and gamma-delta T cells, the concept of IL-17-secreting CD4+ T helper cells (Th17), distinct from Th1 and Th2, recently emerged. Herein, we discuss arguments in favor of a Th17-mediated alternative pathway of allograft rejection based on clinical and experimental observations drawn from the literature.

IL-17 production elicited by allo-major histocompatibility complex class II recognition depends on CD25posCD4pos T cells.

Background: Interleukin (IL)-17 is involved in autoimmune inflammatory disorders and naturally occurring CD25pos regulatory T cells were shown to promote IL-17 synthesis. Because IL-17 is overproduced in certain types of allograft rejection, it is important to characterize the cells responsible for IL-17 synthesis and to define how IL-17 is regulated during alloimmune responses.

Methods: Splenic CD4pos T cells were isolated from C57BL/6 mice and fractionated according to CD25 expression.

Endotoxin hyperresponsiveness upon CD4+ T cell reconstitution in lymphopenic mice: control by natural regulatory T cells.

Natural CD4(+)CD25(+) regulatory T cells (nTreg) have been shown to control graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). Herein, we considered the possibility that the beneficial action of nTreg upon immune reconstitution in lymphopenic hosts involves dampening of the inflammatory response induced by bacterial products. We first observed that transfer of syngeneic CD4(+)CD25(-) T cells in RAG-deficient mice dramatically enhanced release of inflammatory cytokines and associated pathology upon endotoxin injection.

Donor T-cell development in host thymus after heterotopic limb transplantation in mice.

We developed a mouse model of heterotopic limb transplantation in which we took advantage of Thy1.1 and Thy1.2 congenic strains to track and characterize donor T cells, to determine the role of recipient's thymus in mixed T-cell chimerism induction as well as transplant immunocompetence.

Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.

Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA(+)CD4(+) T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-alpha and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4(+) T cells.

Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression.

Background: Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients.

Methods: We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background.