Agranulocytosis after cocaine use: a case of suspected levamisole contamination in Belgium

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Immune Complex Glomerulonephritis in a Patient with Myelodysplastic Syndrome with Ring Sideroblasts Treated with Luspatercept

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders distinguished by dysplastic bone marrow and peripheral blood cells, ineffective hematopoiesis, and an increased risk of developing acute myeloid leukemia (AML). MDS with ring sideroblasts (MDS-RS) is a favorable outcome subtype with a lower frequency of AML transformation. The FDA recently approved luspatercept for the treatment of patients with very-low-, low-, and intermediate-risk MDS-RS who have failed to correct anemia with an erythropoiesis-stimulating agent (ESA) and require two units of red blood cells over an eight-week period. This drug’s pharmacology is based on the critical role of the transforming growth factor-beta (TGF-β) pathway in regulating erythropoiesis. In this case report, we describe for the first time an acute kidney injury caused by membranoproliferative glomerulonephritis (MPGN) in a patient with MDS-RS who was treated with luspatercept. We propose that a multi-hit hypothesis could explain the immunopathogenesis. A first unknown hit may stimulate IgA immune complex production, whereas luspatercept administration acts as a second hit, causing Smad1-5-8 phosphorylation. This intriguing case report on immune-complex-mediated proliferative glomerulonephritis following luspatercept treatment generates hypotheses and stimulates further research in this area

Immune complex glomerulonephritis in a patient with myelodysplastic syndrome with ring sideroblasts treated with luspatercept

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders distinguished by dysplastic bone marrow and peripheral blood cells, ineffective hematopoiesis, and an increased risk of developing acute myeloid leukemia (AML). MDS with ring sideroblasts (MDS-RS) is a favorable outcome subtype with a lower frequency of AML transformation. The FDA recently approved luspatercept for the treatment of patients with very-low-, low-, and intermediate-risk MDS-RS who have failed to correct anemia with an erythropoiesis-stimulating agent (ESA) and require two units of red blood cells over an eight-week period. This drug's pharmacology is based on the critical role of the transforming growth factor-beta (TGF-beta) pathway in regulating erythropoiesis. In this case report, we describe for the first time an acute kidney injury caused by membranoproliferative glomerulonephritis (MPGN) in a patient with MDS-RS who was treated with luspatercept. We propose that a multi-hit hypothesis could explain the immunopathogenesis. A first unknown hit may stimulate IgA immune complex production, whereas luspatercept administration acts as a second hit, causing Smad1-5-8 phosphorylation. This intriguing case report on immune-complex-mediated proliferative glomerulonephritis following luspatercept treatment generates hypotheses and stimulates further research in this area

Systemic mastocytosis with myeloid sarcoma and B-CLL : molecular and clonal heterogeneity in a rare case of SM-AHN with review of literature

Background Systemic mastocytosis (SM) is a rare myeloproliferative disease that results from a clonal proliferation of abnormal mast cells in one or more extra-cutaneous organs. Systemic mastocytosis with an associated hematological neoplasm (SM-AHN) is the second most common subgroup and is diagnosed when WHO criteria for both SM and a hematological neoplasm of non-mast cell lineage are met. The SM-AHN category as currently proposed is highly heterogeneous in terms of pathogenesis, clinical presentation, and prognosis. Case presentation We present the first reported case of SM-AHN associated with two hematological malignancies of different lineages, a monocytic myeloid sarcoma and a B-cell chronic lymphatic leukemia. Cytogenetic and molecular analyses revealed a distinct clonal origin of the two associated malignancies. The SM-myeloid sarcoma clone demonstrated an abnormal karyotype, trisomy 8 and del(13)(q12.3q14.3), as well as mutations in KITD816V, DNMT3A and RUNX1. The DNMT3A mutation could be detected years before disease onset, supporting its potential role as early driver of leukemogenesis. No genetic aberrations could be identified in the CLL clone, which is assumed to present coincidentally. Conclusions This report highlights the importance of full diagnostic work-up in SM patients in whom an associated hematological malignancy is suspected. Moreover, the importance of genetic analysis is highlighted, as it provides additional insights in the underlying clonal pathogenesis of different phenotypes, can aid in risk stratification, and may help identify potential therapy targets

GATA2 deficiency and haematopoietic stem cell transplantation : challenges for the clinical practitioner

GATA2 deficiency, first described in 2011, is a bone marrow failure disorder resulting in a complex haematological and immunodeficiency syndrome characterised by cytopenias, severe infections, myelodysplasia and leukaemia. The only curative treatment is allogeneic haematopoietic stem cell transplantation (HSCT). Although knowledge on this syndrome has greatly expanded, in clinical practice many challenges remain. In particular, guidelines on optimal donor and stem cell source and conditioning regimens regarding HSCT are lacking. Additionally, genetic analysis of GATA2 is technically cumbersome and could easily result in false-negative results. With this report, we wish to raise awareness of these pitfalls amongst physicians dealing with haematological malignancies and primary immunodeficiencies