Utility of the refined EBMT diagnostic and severity criteria 2023 for sinusoidal obstruction syndrome/veno-occlusive disease.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2-13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted.

RUNX1 rearrangement in mature B-cell acute lymphoblastic leukemia with non-L3 morphology.

Mature B-cell acute lymphoblastic leukemia (ALL) is defined by the expression of light chain-restricted surface immunoglobulin (sIg) and usually has features of the leukemic phase of Burkitt lymphoma including FAB-L3 morphology and MYC rearrangement. Recently, another distinct entity in childhood mature B-cell ALL has been characterized as non-L3 morphology and KMT2A rearrangement. Here we report an unusual case of mature B-cell ALL that presented with RUNX1 rearrangement. A 65-year-old male was admitted to our department for thorough examination of leukocytosis and thrombocytopenia. The patient's bone marrow was hypercellular and infiltrated with 97.8% myeloperoxidase-negative, medium-to-large-sized blasts without cytoplasmic vacuoles. Immunophenotypes were characterized by the presence of light chain-restricted sIg and the lack of immature markers, indicating a diagnosis of mature B-cell ALL with L2 morphology: sIg-κ+, CD19+, CD20+, CD22+, CD79a+, TdT-, and CD34-. G-banding combined with spectral karyotyping showed the following complex karyotype: 45,X,der(Y;10)(p10;q10),del(13)(q?),inv(21)(p13q22.1). Fluorescence in situ hybridization revealed separated signals of RUNX1 at 21q22.1, whereas rearrangements of MYC and KMT2A were not found. To our knowledge, inv(21)(p13q22.1) involving RUNX1 is a novel cytogenetic aberration and this is the first case of mature B-cell ALL that presented with RUNX1 rearrangement. Thus, RUNX1 may be implicated in the pathogenesis of mature B-cell ALL showing non-L3 morphology without MYC rearrangement.

Early diagnosis of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation, with modified diagnostic criteria including refractory thrombocytopenia.

Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed a retrospective study to investigate the Cairo diagnostic criteria, in which SOS was defined as the development of two or more in seven events, including transfusion-refractory thrombocytopenia. Among 154 cases of allogeneic HSCT, 10 cases of SOS using the European Society for Blood and Marrow Transplantation criteria (EBMT16) as the reference standard were identified. The original Cairo criteria could diagnose SOS 5 days earlier than any other established criteria, with some false-positive results (sensitivity = 100.0%; specificity = 72.2%). When the cutoff was set to three events for the Cairo criteria, the diagnosis of SOS could be made 3 days earlier than that using the EBMT16 criteria, with comparable precision (specificity = 86.1%). The accuracy of the Cairo criteria improved further when the cutoff point was set to four (specificity = 93.8%). The fulfillment of the Cairo criteria was associated with high mortality. Based on our results, the Cairo criteria were also considered clinically useful, especially at three or four cutoff points. Further studies are required to validate and refine the criteria.