Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT. Planning post-transplant maintenance treatment as part of a prophylaxis strategy is now feasible. Monitoring biomarkers of residual disease and post-transplant chimerism after allo-HCT allows a preemptive strategy. Within the frame of the 14th annual workshops of the Francophone Society for Bone Marrow Transplantation and Cell Therapy, the working group reviewed the literature and discussed novel strategies and therapies used to prevent relapse post-allo-HCT. Innovative drugs have been developed recently. Their toxicity profile allows their use post-allo-HCT, albeit with precaution. We reviewed the use of FLT3 inhibitors for AML, BCR::ABL inhibitors for Philadelphia chromosome for ALL, hypomethylating agents and Bcl-2 inhibitors for AML and MDS. The indications of immunomodulation and infusion of donor lymphocytes have been reviewed. Finally, we outlined methods of follow-up and support for patients receiving these prophylactic treatments.

Plasma cell neoplasms (PCN) have infrequently been reported in patients with myelodysplastic syndrome (MDS) and even more rarely in those with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). We report the clinicopathologic features of 26 patients with bone marrow myelodysplasia accompanied by PCN, including 21 patients with MDS and 5 with MDS/MPN. The clinicopathologic features of the MDS/MPN-PCN were compared to those of the MDS-PCN group and 68 cases of MDS/MPN without PCN, respectively. The MDS/MPN-PCN group was notable for increased reticulin fibrosis > grade 1 when compared to both the MDS/MPN (p = 0.007) and MDS-PCN (p = 0.02) groups. MDS/MPN-PCN was associated with worse overall survival when compared with MDS-PCN (p = 0.03) and but not with MDS/MPN. Notably, hemoglobin level <8 g/dl (p = 0.008), and IDH2 somatic mutation (p = 0.003) were independent predictors of poor overall survival in all patients with MDS/MPN. Analysis of larger cohorts is required to confirm these associations and provide an insight into the pathogenesis.

The red cell distribution width (RDW) is a standard variable reported in the complete blood count. It has been found to have a consistent relationship to life expectancy in older individuals, prognosis in patients with cardiovascular disease, outcome in those with hematological and non-hematological neoplasms and in a variety of medical circumstances such as non-cardiovascular or cancer related critical illness and postoperative outcome from various procedures. This report reviews some of the key medical publications establishing these relationships with RDW. The precise pathobiological processes that explain the predictive value of the RDW in this wide array of circumstances or why an alteration in erythropoiesis (exaggerated red cell size variation) occurs is uncertain. The possible role of inflammation has been one hypothesis considered, but not established.

Acute febrile neutrophilic dermatosis, or Sweet\'s syndrome, is characterized by tender, edematous papules and plaques, favoring the upper extremities and the head and neck regions. The classic variant of Sweet\'s syndrome involves a predominantly neutrophilic dermal infiltrate on histopathology. However, histiocytoid Sweet\'s syndrome has been noted to have a primary histiocytoid mononuclear infiltrate and is typically found in patients with malignancies such as myelodysplasia. This case report discusses the treatment of histiocytoid Sweet\'s syndrome in an immunocompromised patient with a recent history of Mycobacterium avium complex infection and latent tuberculosis in the setting of myelodysplastic syndrome.

Hypomethylating therapies using decitabine or azacitidine are actively investigated to treat acute myeloid leukemia, myelodysplastic syndromes, as maintenance therapy after allogenic stem cell transplant and hemoglobinopathies. The therapeutic mechanism is to de-repress genes that have been turned off through oncogenesis or development via methylation. The therapy can be non-cytotoxic at low dosage, sparing healthy stem cells and operating on committed precursors. Because the methods of determining maximum tolerated dose are not well suited to this paradigm, and because the mechanism of action, which is depletion of DNA methylase 1 (DNMT1), is complex and dependent on passing through a cell cycle, a pharmacodynamic assay that measures DNMT1 can inform clinical trials aimed at establishing and improving therapy. Herein, we provide an assay that measures DNMT1 relative levels in circulating T cells of peripheral blood.

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat\'s therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

The interaction of acute myeloid leukaemic (AML) blasts with the bone marrow (BM) microenvironment is a major determinant governing disease progression and resistance to treatment. The constitutive expression of E-selectin in the vascular compartment of BM, a key endothelial cell factor, directly mediates chemoresistance via E-selectin ligand/receptors. Despite the success of hypomethylating agent (HMA)-containing regimens to induce remissions in older AML patients, the development of primary or secondary resistance is common. We report that following treatment with 5-azacitidine, promoter regions regulating the biosynthesis of the E-selectin ligands, sialyl Lewis X, become further hypomethylated. The resultant upregulation of these gene products, in particular α(1,3)-fucosyltransferase VII (FUT7) and α(2,3)-sialyltransferase IV (ST3GAL4), likely causes functional E-selectin binding. When combined with the E-selectin antagonist uproleselan, the adhesion to E-selectin is reversed and the survival of mice transplanted with AML cells is prolonged. Finally, we present clinical evidence showing that BM myeloid cells from higher risk MDS and AML patients have the potential to bind E-selectin, and these cells are more abundant in 5-azacitidine-non-responsive patients. The collective data provide a strong rationale to evaluate 5-azacitidine in combination with the E-selectin antagonist, uproleselan, in this patient population.

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet\'s syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

We report the case of the youngest patient described with VEXAS syndrome associated with MDS-IB1, successfully treated with azacitidine-venetoclax and allogeneic stem cell transplant.

The classification of myeloid neoplasms continues to evolve along with advances in molecular diagnosis, risk stratification and treatment of disease. An approach for disease classification has been grounded in international consensus that has facilitated understanding, identification and management of molecularly heterogeneous entities, as well as enabled consistent patient stratification into clinical trials and clinical registries over time. The new World Health Organization (WHO) and International Consensus Classification (ICC) Clinical Advisory Committee releasing separate classification systems for myeloid neoplasms in 2022 precipitated some concern amongst haematopathology colleagues both locally and internationally. While both classifications emphasise molecular disease classification over the historical use of morphology, flow cytometry and cytogenetic based diagnostic methods, notable differences exist in how morphological, molecular and cytogenetic criteria are applied for defining myelodysplastic neoplasms (MDS) and acute myeloid leukaemias (AML). Here we review the conceptual advances, diagnostic nuances, and molecular platforms required for the diagnosis of MDS and AML using the new WHO and ICC 2022 classifications. We provide consensus recommendations for reporting bone marrow biopsies. Additionally, we address the logistical challenges encountered implementing these changes into routine laboratory practice in alignment with the National Pathology Accreditation Advisory Council reporting requirements for Australia and New Zealand.