Natural history of clonal haematopoiesis seen in real-world haematology settings.

Recursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real-world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbouring canonical DNMT3A/TET2/ASXL1 mutations alone ('sole DTA') versus all other groups ('non-sole DTA'). TET2, rather than DNMT3A, was the most prevalent mutation in the real-world setting. Sole DTA patients did not progress to myeloid neoplasm (MN) in the absence of acquisition of other mutations. Contrastingly, 14 (20.1%) of 67 non-sole DTA patients progressed to MN. CHRS assessment showed a higher frequency of high-risk CH in non-sole DTA (vs. sole DTA) patients and in progressors (vs. non-progressors). RUNX1 mutation conferred the strongest risk for progression to MN (odds ratio [OR] 10.27, 95% CI 2.00-52.69, p = 0.0053). The mean variant allele frequency across all genes was higher in progressors than in non-progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post-CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN.

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions.

TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 variant allele frequency (VAF) > 50%. In multivariate analysis, unadjusted Cox models revealed the following variables as independent risk factors for mortality: AML (vs. MDS) (hazard ratio [HR]: 2.50, confidence interval [CI]: 1.4-4.4, p = 0.001), complex karyotype (HR: 3.00, CI: 1.4-6.1, p = 0.003), multihit status (HR: 2.30, CI 1.3-4.2, p = 0.005), and absence of hematopoietic cell transplant (HCT) (HR: 3.90, CI: 1.8-8.9, p = 0.0009). Clonal dynamic modeling showed a significant reduction in TP53 VAF with front-line hypomethylating agents. These findings clarify the impact of specific covariates on outcomes of TP53-aberrant myeloid neoplasms, irrespective of the diagnosis of MDS versus AML, and may influence HCT decisions.

Human platelet antigen 1, 2 and 5 gene polymorphisms in Egyptians and their potential association with susceptibility to immune thrombocytopenic purpura in Egyptian patients.

OBJECTIVES: This study determined the incidence of HPA1, HPA2 and HPA5 polymorphisms in 120 Egyptian immune thrombocytopenic purpura (ITP) patients and 120 healthy Egyptian subjects. METHODS: Human platelet antigen (HPA) genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of HPA1 allele a and b was 78.75 and 21.25% in controls, 80.8 and 19.2% in ITP, respectively. HPA2 allele a and b frequency was 86.25 and 13.75% in controls and of 74.6 and 25.4% in patients, respectively. HPA5 allele a and b frequency was 87.5 and 12.5% in controls, in patients it was 85 and 15%, respectively. With the exception of HPA2, no other significant difference was encountered in HPA allele frequency between controls and ITP patients. DISCUSSION: Egyptian HPA profile is closely linked to Middle East and neighboring Arabs. The current study noted that in all the studied HPA systems 1, 2 and 5, the 'a' allele is more prevalent than the b allele; the most frequent genotype was the homozygous a/a genotype. HPA2b frequency, homo- and hetero-zygous HPA2b genotype frequencies were significantly higher in ITP patients compared to controls. CONCLUSION: HPA 2b are 2.37 times more likely to develop ITP compared to those without this allele. The relatively high allele frequency of the HPA-1b in the Egyptian population suggests that this ethnic group has a higher risk of alloimmunization.

Occult Massive Visceral Fat Necrosis Following Therapeutic Hypothermia for Neonatal Encephalopathy.

Therapeutic hypothermia (head or whole-body cooling) improves survival and neurodevelopmental outcome in term newborns with moderate-to-severe encephalopathy. Hypothermia treatment is well tolerated; the most common side effect is thrombocytopenia. In about 1% of infants, focal subcutaneous fat necrosis has been reported. We describe a case of clinically unsuspected massive visceral fat necrosis in a term infant with Apgar score 0 at 1 min ("resuscitated apparently stillborn" infant) who was treated with therapeutic hypothermia for 72 h and expired on the 25th day of life following a neonatal course complicated by severe encephalopathy, pulmonary artery hypertension, persistent thrombocytopenia, hypoglycemia, and severe basal ganglia-thalamic abnormalities on magnetic resonance imaging. Postmortem examination revealed extensive visceral (brown) fat necrosis, involving thoracic, abdominal, and retroperitoneal adipose tissue, with distinctive sparing of the subcutaneous (white) fat. The fulminant-yet clinically occult-visceral fat necrosis seen in this case suggests that (lesser degrees of) fat necrosis may go unrecognized in hypoxic-ischemic newborns, especially in those treated with hypothermia, and underscores the importance of close monitoring of encephalopathic newborns both in the short and long terms for complications of fat necrosis (hypercalcemia and nephrocalcinosis).

Placental Teratoma, Omphalomesenteric Duct Remnant, or Intestinal Organoid (Enteroid) Differentiation: A Diagnostic Dilemma.

We report an unusual case of fully developed fetal intestinal segment(s) within a nodule on the chorionic plate of the placenta of a 27-year-old female patient at 37 weeks gestation with spontaneous vaginal delivery. Gross examination of the placenta revealed a chorionic plate nodule near the insertion of the umbilical cord, which, upon microscopic evaluation, raised the differential diagnostic possibilities of placental teratoma, vitelline/omphalomesenteric duct anomaly, and intestinal organoid differentiation. We discuss the distinguishing features, morphogenesis, and clinical significance of the aforementioned entities and review the pertinent medical literature.

Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature.

Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML. The small lymphoid aggregates noted in his bone marrow were neoplastic in nature and represented bone marrow involvement by a CD5-negative mantle cell lymphoma (MCL) that presented without any associated lymphadenopathy. We reviewed the English medical literature to identify a single case report of simultaneous association of AML and a MCL in the bone marrow. The unusual association presented here suggests an increase in observer awareness to apparently benign lymphoid aggregates in chronic myeloproliferative neoplasms.