American Journal of Hematology最新文献

Symptoms, management and outcomes of patients with immune TTP admitted to the intensive care unit.

In this Japanese registry-based analysis of 9105 adult patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation, a marked difference in survival was observed based on platelet levels: ≤ 20 × 10⁹/L, 20–50 × 10⁹/L, and > 50 × 10⁹/L. The number of patients with thrombocytopenia receiving cord blood (CB, 39%) was significantly larger than those receiving unrelated bone marrow (uBM, 17%) on Day 50 (p < 0.001); however, this difference disappeared on Day 100 posttransplantation (both 11%, p = 0.4).

The major anticoagulant Protein S (PROS1) also contributes to the phagocytosis of apoptotic cells by bridging exposed phosphatidylserine (PtdSer) to the MerTK receptor on macrophages (efferocytosis). Whether PROS1 is involved in the splenic clearance of PtdSer-positive senescent and altered erythrocytes such as erythrocyte ghosts (eryghosts) is unknown. Here, we investigate the contribution of PROS1 and MerTK to the phagocytosis of intact RBC and eryghosts in healthy subjects and patients with sickle cell disease (SCD). We show that PROS1 enhances the phagocytosis of ionomycin-treated PtdSer-positive erythrocytes and of eryghosts generated in vitro. We confirm that eryghosts circulate in patients with SCD at higher levels than in healthy subjects and observe increased hemolysis and decreased levels of plasmatic PROS1 in patients with the highest concentration of eryghosts. The proportion of circulating eryghosts is correlated with the intensity of hyposplenism, and eryghosts are less frequently observed in sections of SCD compared to control spleens. We demonstrate that circulating eryghosts are procoagulant and adhere to endothelial cells. In SCD, PROS1 enhances their phagocytosis in a MerTK-dependent manner but has no such effect on intact erythrocytes. PROS1 is therefore involved in erythrophagocytosis, a physiological process insufficient in patients with SCD due to intense intravascular hemolysis and hyposplenism, leading to PROS1 consumption and the abnormal persistence of eryghosts in circulation. PROS1 deficiency may in turn initiate a pathogenic loop, enhancing unregulated activation of coagulation and defective clearance of procoagulant and adherent eryghosts. This deeper understanding of physiological and pathological erythrophagocytosis opens new therapeutic approaches targeting PROS1 in SCD.

Acute renal failure due to cast nephropathy (CAN) is a severe complication of multiple myeloma (MM). Here, we aimed to identify parameters associated with renal outcomes and survival in newly diagnosed MM patients with CAN-related acute renal failure and to validate the IMWG criteria for renal response. CAN diagnosis was based on biopsy or clinical assessment. Of 787 registered patients, 354 met the inclusion criteria, requiring at least two therapy cycles with documented chemotherapy response, renal response, and eGFR. Baseline free light chain (FLC) levels (median 6825.65 mg/L) decreased below 500 mg/L in 67.8% of patients. According to IMWG classification, renal complete response, partial response, and minimal response were achieved in 33.9%, 19.5%, and 28.0% of patients, respectively. The best eGFR values > 60 mL/min/1.73 m² were observed in 33.9% of patients, while 33.3%, 22.3%, and 10.5% had best eGFR values of 30–59, 15–29, and < 15 mL/min/1.73 m², respectively. Renal response correlated with baseline FLC levels, IgG kappa, eGFR, and ECOG status in multivariate analysis, as well as with myeloma response and FLC reduction in univariate analysis. Median overall survival was 77.6 months. Survival correlated with age, myeloma response, ECOG status, FLC kappa type, baseline eGFR, standard-risk cytogenetics, and calcium levels, among other factors. A comparison of IMWG renal response criteria with classification based solely on best eGFR showed similar utility. Of 136 patients requiring dialysis, 80 (58.8%) were able to discontinue dialysis during therapy. Bortezomib containing myeloma therapy, along with significant FLC reduction, was associated with favorable outcome.

Descriptive graph of all patients tested in this cohort who were found to have new MG diagnoses through testing (11.8%), and the percentage of patients with a clinically significant monoclonal protein test (0.4%). Clinically significant tests were those that led to a new lymphoplasmacytic diagnosis or uncovered MG as the source of the patient's anemia for which they received monoclonal protein testing.

The tumor necrosis factor (TNF)-receptor superfamily 8 receptor CD30 molecule is expressed in all tumor cells of Hodgkin lymphoma and anaplastic large cell lymphoma but is only weakly expressed in a small subset of large lymphoid cells in normal peripheral lymphoid tissues. This makes this molecule an important target for the diagnosis and treatment of CD30-expressing lymphomas. We describe the road to the discovery of the CD30 molecule and the way CD30 has contributed to more precise diagnosis and classification of lymphomas. Moreover, we address how anti-CD30 immunotherapy was developed and the impact of the anti-CD30-auristatin conjugate and anti-CD30 CAR-T cells in treating CD30-expressing lymphomas.