ABSTRACTGiven the dismal prognosis for patients with TP53‐mutated acute myeloid leukemia (AML), the optimal donor for those undergoing allogeneic hematopoietic cell transplantation (allo‐HCT) remains unclear. We retrospectively analyzed adult patients with TP53‐mutated AML who underwent first allo‐HCT in CR1 between 2010 and 2021. Outcomes were compared among using a haploidentical donor (Haplo), a matched sibling donor (MSD), and a 10/10 matched unrelated donor (MUD). The analysis comprised 451 patients, including 86 Haplo, 117 MSD, and 248 MUD. Patients in the three groups were transplanted during a similar period. Haplo, MSD, and MUD groups experienced similar incidences of Day 180 Grades II–IV aGVHD (30.9% vs. 23.6% vs. 28.3%), Grades III–IV aGVHD (13.6% vs. 10.1% vs. 9.1%), 2‐year cGVHD (28.9.% vs. 30.9% vs. 25.6%) and extensive cGVHD (10.9% vs. 16.1% vs. 13.3%). By multivariate analysis, the outcomes were similar in the three groups. The MSD group was associated with a similar 2‐year overall survival (OS: 33.9%; p = 0.799), leukemia‐free survival (LFS: 30.5%; p = 0.956), relapse incidence (RI: 54.2%; p = 0.497), non‐relapse mortality (NRM: 15.3%; p = 0.368), and GVHD‐free, relapse‐free survival (GRFS: 21.8%, p = 0.957) when compared with the Haplo group (2‐year OS: 46.7%, LFS: 37.4%, RI: 40.8%, NRM: 21.7%, GRFS: 25.7%). The MUD group also experienced a similar 2‐year OS (36.9%; p = 0.892), LFS (31%; p = 0.904), RI (50.8%; p = 0.521), NRM (18.2%; p = 0.368) and GRFS (21.9%; p = 0.383) when compared with the Haplo group. In conclusion, outcomes of patients with TP53‐mutated AML undergoing allo‐HCT from a haploidentical donor were comparable to those from an MSD or 10/10 MUD HCT.

A 69-year-old man with a 10-year history of untreated chronic lymphocytic leukemia (CLL) was referred for his annual hematology follow-up. He was in good general condition (ECOG 1), with no lymphadenopathy or splenomegaly on physical examination. His blood count showed: hemoglobin 125 g/L, platelet count 217 × 109/L, and white blood cell count 66.96 × 109/L with a marked lymphocytosis (94%, 62.94 × 109/L). Blood film examination revealed a monomorphic population of small lymphocytes and smudge cells with typical features of CLL. However, 15% of lymphocytes displayed partial nuclear extrusion (upper images, all images May-Grünwald-Giemsa, ×63 objective), a finding already observed in this patient's previous blood films. To assess whether this morphological abnormality occurred in vivo, a blood film was directly performed at the patient's bedside using a non-anticoagulated sample, in parallel with blood samples collected in EDTA and lithium heparin tubes. Strikingly, nuclear extrusion was clearly observed in the blood films from both anticoagulated samples, EDTA (top) and lithium heparin (bottom left), but was completely absent in the non-anticoagulated blood film (bottom right). These findings indicate that, in this case, nuclear extrusion is an in vitro phenomenon occurring in anticoagulated blood. A few cases of nuclear extrusion in CLL lymphocytes have been reported in the literature [1-3], but the underlying mechanism remains unclear. Some authors have argued against an in vitro artefact, citing the consistent presence of this morphological feature in repeated samples from the same patient [2]. However, those observations were limited to heparin-anticoagulated samples. Other authors have suggested that nuclear extrusion reflects the intrinsic fragility of CLL lymphocytes [3]. Our findings challenge this interpretation: in our case, smudge cells (widely recognized as a marker of lymphocyte fragility, resulting from mechanical disruption during film preparation) were present in both anticoagulated and non-anticoagulated blood samples. In contrast, nuclear extrusion was only observed in the anticoagulated samples. This discrepancy calls into question the hypothesis that nuclear extrusion is related to intrinsic cellular fragility. Although the number of reported cases remains too limited to draw firm conclusions, our observation supports the hypothesis that this rare phenomenon only occurs in vitro, developing in anticoagulated blood, and does not appear to have any clinical impact on CLL progression. Moreover, it highlights the importance of performing a non-anticoagulated blood film at the patient's bedside when such atypical morphological findings are observed. The authors declare no conflicts of interest. Data sharing is not applicable to this article.

The authors declare no conflicts of interest.

ABSTRACTMycoplasma pneumoniae (MP), primarily a respiratory pathogen, can cause extra‐pulmonary manifestations including cold agglutinin syndrome (CAS). We conducted a national, multicenter, observational, ambispective study to describe the characteristics, risk factors, and outcomes of MP‐associated CAS. Adult patients hospitalized for a MP‐infection with CAS (hemolytic anemia with hemoglobin < 10 g/dL and C3 positive direct anti‐globulin test) were included. Recovery was defined as hemoglobin > 10 g/dL off therapy. We also compared MP‐infected patients with or without CAS. Sixty patients (51.7% of females; median age of 48.5 years) were included. CAS was diagnosed a median of 10 days after MP‐infection symptoms onset. At diagnosis, the median hemoglobin level was 6.9 g/dL, and 71.7% of patients received red blood cell transfusions. Intensive care unit (ICU) admission was required in 45% of patients, and 16.7% experienced a venous thromboembolic event (VTE). Seventeen patients (28.3%) received glucocorticoids alone, while 40 (66.7%) did not receive any specific treatment for CAS. After a median follow‐up of 56 (30–83) days, 90% of patients achieved recovery, while 2 patients (3.3%) died from sepsis and pulmonary embolism. Glucocorticoid use did not significantly impact the rate or timing of recovery. Compared with MP‐infected patients from the MYCADO cohort study (n = 1267), CAS patients had significantly more VTE (p < 0.0001) and ICU admissions (p = 0.03). MP‐associated CAS typically occurs 10 days after the first symptoms of MP infection and is associated with ICU admissions and VTE. Overall, the prognosis of CAS is good, and glucocorticoids do not appear to influence outcomes.

A male patient, now 67-years-old, was referred in 1997 for evaluation of suspected hereditary hemochromatosis and for initiation of regular phlebotomy. His blood count showed hemoglobin concentration (Hb) 166 g/L, mean corpuscular volume (MCV) 112.7 fL, mean corpuscular hemoglobin (MCH) 37.8 pg, and mean corpuscular hemoglobin concentration (MCHC) 33.6 g/dL. Platelet and leukocyte counts were normal. Serum iron was 154 μg/dL, transferrin 170 mg/dL, transferrin saturation 90.7%, and ferritin 956.5 ng/mL. Total bilirubin was 1.82 mg/dL with a direct fraction of 0.51 mg/dL. Haptoglobin was 79 mg/dL. Abdominal ultrasonography showed hepatomegaly with a homogeneous liver texture, which was confirmed by computed tomography showing mild parenchymal hyperdensity, likely reflecting increased hepatic iron deposition. Liver biopsy demonstrated grade IV/IV hemosiderosis and septal fibrosis. Based on these findings, a diagnosis of hereditary hemochromatosis and Gilbert syndrome was favored, and regular phlebotomy was commenced. However, genetic testing for common HFE mutations (H63D, C282Y, and S65C) was negative, and careful examination of a blood smear (upper images and lower left, May-Grünwald-Giemsa, ×100 objective) revealed stomatocytes, knizocytes (stomatocytes with two indentations), irregularly contracted cells, spherocytes, target cells, and occasional schistocytes. The reticulocyte count was consistently elevated (~230 × 109/L). Osmotic fragility testing showed increased red cell resistance. Red cell cytograms showed a marked increase in cells with an increased hemoglobin concentration (lower right image, Advia). Hemoglobin electrophoresis and assays for glucose-6-phosphate dehydrogenase and pyruvate kinase were normal. With later access to molecular diagnostics, the diagnosis of hereditary xerocytosis, suspected from the blood film, was confirmed. A next-generation sequencing (NGS) panel for hereditary hemolytic anemias revealed the presence of the missense variant c.5975C>T p.(Thr1992Met) in the PIEZO1 gene, apparently in homozygosity, resulting in the substitution of threonine with methionine at position 1992. The PIEZO1 gene encodes a component of the Piezo-type mechanosensitive ion channel. Pathogenic variants in PIEZO1 are associated with dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and constitutional abnormalities. The variant is listed in the ClinVar database (ID: 3256323) as a variant of uncertain significance (VUS) [1], but our patient demonstrates that it is pathogenic. Hereditary xerocytosis, also known as the dehydrated form of hereditary stomatocytosis, is a rare inherited hemolytic anemia characterized by increased cation permeability, normal or elevated intracellular cation content, and cellular dehydration [2, 3]. The disorder follows an autosomal dominant inheritance pattern with variable penetrance. It is typically milder than the overhydrated variant. Most cases are associated with a gain-of-function mutation in the PIEZO1 gene. Notably, hepatic iron overload can be disproportionately severe relative to the degree of anemia [3]. Diagnosis is important, both because of the possibility of iron overload and because splenectomy should be avoided. The patient has continued on regular phlebotomy, and ultrasonography of the liver is now normal. The authors declare no conflicts of interest. The authors have nothing to report.

ABSTRACTAnemia, a global health challenge affecting a quarter of the global population, results from diverse causes such as nutritional deficiencies, chronic diseases, and genetic factors. It disproportionately impacts women of reproductive age and children, leading to significant morbidity and mortality. While high‐altitude populations face unique diagnostic challenges due to natural hemoglobin increases, the current World Health Organization cutoffs often overestimate anemia in these regions. Altitude corrections significantly alter prevalence rates, particularly in South American children, leading to misdiagnosis. Proposed solutions include population‐specific thresholds and iron status markers like serum hepcidin, though economic constraints and limited test availability remain challenges. Tailored strategies informed by genetic research highlight adaptations in Tibetan and Ethiopian highlanders, demonstrating the need for region‐specific approaches. Socioeconomic factors exacerbate anemia in high‐altitude areas. Addressing anemia requires updated diagnostic criteria, personalized strategies, and increased awareness to ensure accurate assessments and interventions in diverse populations, especially those residing at high altitudes.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is pivotal for hematological malignancies but faces challenges in delayed platelet engraftment, poor graft function (PGF), and bleeding risks. Hetrombopag, a thrombopoietin receptor agonist, was evaluated to enhance platelet recovery posttransplant. Patients undergoing allo-HSCT were randomized on Day 3 Post-Infusion into low-dose (2.5 mg/day), high-dose (5 mg/day) hetrombopag groups, or a control group receiving thrombopoietin (300 U/kg/day). Endpoints included platelet/neutrophil engraftment time, PGF incidence, transfusion needs, and safety. Among 212 analyzed patients, platelet engraftment was faster in hetrombopag groups (median 13 days) versus controls (15 days; p = 0.0022), with no dose-dependent difference (p = 0.0593). Neutrophil engraftment was also accelerated (13 vs. 15 days; p = 0.0001). PGF incidence was lower in hetrombopag groups (5.04%) versus controls (13.7%; p = 0.027). The experimental group required fewer platelet transfusions (p = 0.002), had reduced gastrointestinal bleeding, and lower costs. Secondary platelet recovery failure showed no intergroup differences. Hetrombopag safely accelerates platelet and neutrophil engraftment, reduces PGF risk, and decreases transfusion dependency post-allo-HSCT. Low-dose hetrombopag demonstrated efficacy equivalent to high-dose, offering a cost-effective strategy to improve transplant outcomes. Trial Registration: ChiCTR2200057764.

FDG avid bilateral ureteral lesions.[Image: see text]