Annals of Hematology最新文献

In most cases of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK + ALCL), long-term survival is achieved using CHOP therapy. However, some cases have a poor prognosis. Here, we investigated the clinical impact of TP53 deletion on adult ALK + ALCL patients via a multicenter, retrospective analysis. TP53 deletion was evaluated by fluorescence in situ hybridization (FISH) using paraffin sections of lymphoma samples. To re-evaluate the FISH results, whole genome copy number changes were analyzed in DNA extracted from paraffin sections using OncoScan analysis. Fourteen patients treated with first-line chemotherapy enrolled at six centers were analyzed. All patients received CHOP-based therapy as initial therapy. The 5-year progression-free survival (PFS) and overall survival (OS) of the 14 patients were 28.6% (median 7 months) and 57.1% (median 99 months), respectively. FISH analysis revealed 6 (43%) patients were positive for TP53 deletion (deletion group) and 8 (57%) were negative (non-deletion group). All six patients in the deletion group were diagnosed at an advanced stage; five were refractory to initial treatment, one relapsed after treatment, and all patients died of ALK + ALCL. The median PFS was 3.5 months in the deletion group and 76 months in the non-deletion group. The median OS was 7 months in the deletion group and has yet to be confirmed in the non-deletion group. OncoScan analysis showed TP53 copy number reduction in the deletion group and no TP53 copy number abnormalities in the non-deletion group. This study suggests that TP53 deletion is a poor prognostic factor in ALK + ALCL treated with CHOP-based therapy.

Managing chronic myeloid leukemia during pregnancy presents significant challenges, with limited treatment options available depending on the stage of pregnancy. All existing tyrosine kinase inhibitors are considered teratogenic, especially during the first trimester and should be avoided. In this case report, we detail the successful, unplanned dichorionic diamniotic twin pregnancy of a patient with chronic-phase myeloid leukemia previously resistant to imatinib and dasatinib who was exposed to the allosteric tyrosine kinase inhibitor asciminib during the early weeks of gestation. Upon confirmation of the pregnancy, asciminib was discontinued, and the patient was treated with pegylated interferon. The patient developed preeclampsia, and the twins were delivered prematurely via cesarean section. No other abnormalities were observed in the newborns. During her pregnancy, the patient experienced a loss of the major molecular response; however, she regained it within two months of resuming asciminib after giving birth. To our knowledge, this case represents the first report of a twin pregnancy during asciminib treatment.

This study investigates the burden, phenotypes, progression, and outcomes of familial hematological malignancies (FHM) through clinical evaluation, gene panel testing, and whole exome sequencing, highlighting the significance of identifying genetic causes for personalized treatment. Over six years, 357 patients initially diagnosed with bone marrow failure (BMF) were evaluated, with 152 patients lacking identifiable causes undergoing further analysis. Among these, 53 (34.9%) exhibited features of inherited BMF syndromes, and 13 (24.5%) developed FHM. In a separate cohort of 27 patients with inherited immunodeficiency disorders, 8 (29.6%) developed FHM associated with NHEJ1 or LYST variants, underscoring the familial clustering of hematologic disorders. Notably, 6 of 7 patients from the same family (family-1) with homozygous NHEJ1 variants progressed to secondary myelodysplastic syndrome (sMDS), acute myeloid leukemia (AML), or lymphoma. Among 780 patients diagnosed with hematological malignancies during the study period, 45 (5.8%) were confirmed to have FHM, with 33 patients enrolled for detailed analysis. Of these, 16 (48.5%) had DNA-repair deficiencies (DNA-RD), including eight with Fanconi anemia, six with NHEJ1 variants, and two with BRCA2 mutations. The remaining 17 patients presented conditions such as familial myeloproliferative neoplasms, dyskeratosis congenita (DC) [TERT, DKC1 variants], and Chediak-Higashi syndrome. Two siblings (family-3) with a rare TERT variant and a unique DC phenotype developed sMDS after prolonged BMF. Patients with DNA-RD were younger and exhibited higher rates of growth failure, recurrent infections, and endocrinopathies. These cases frequently progressed to sMDS or AML. A comparative analysis of 319 individuals with DNA double-strand break repair deficiencies revealed a 45% frequency of hematological malignancies. Lymphoma was most common in Nijmegen breakage syndrome (79.4%) while MDS/AML was prevalent in Cernunnos deficiency (66.6%). The findings emphasize the importance of early diagnosis, genetic testing, and personalized management, including timely transplantation, to improve outcomes in FHM. This research underscores the need for clinical awareness and surveillance to facilitate timely interventions and mitigate disease progression.

For many hematological malignancies (HMs) survival among older patients is compromised. We want to test the most up-to-date age-group-specific survival differences in five hematological malignancies, Hodgkin lymphoma (HL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and myeloproliferative diseases (MPD) in Sweden (SE) and compared these to Denmark, Finland and Norway. For analysis we apply a recently published metric for comparing and visualizing age-group-specific relative survival differences using data from the NORDCAN database between 1972 and 2021. Periodic changes in age-related deviation in SE survival showed increasing differences for AML and MM while for the other HMs the differences declined in the course of time. Country-specific differences were observed, for Finnish male CLL and female MPD deviations were larger than those for the other countries, both of which were explained by the deviant survival of the oldest patients. Age-related deviations in 5-year survival increased for AML and MM for which survival improvements have been achieved through intense treatment regimens but these are not offered to old patients because of risk of complications. Paradoxically, improving overall survival in AML and MM has contributed to the widening of the age gaps. For the remaining HMs, age-related deviations declined with time as even old patients benefitted from the survival improvements; most notably female MPD and CLL patients had hardly any age gaps. Age disparities are an issue in hematological malignancies, and an intense search for novel treatments also includes old patients with an example of success as a novel drug venetoclax.

Sideroblastic anemias (SAs) represent a heterogeneous group of rare hematological disorders characterized by iron accumulation in mitochondria of erythroblasts with ineffective erythropoiesis. SAs are categorized into acquired and congenital forms. Acquired, secondary, and clonal, SA is rare in pediatric populations. Congenital SA (CSA) is classified into syndromic and non-syndromic forms. Herein, we describe three cases of pediatric patients with SA. The diagnosis of SA was based on the presence of type 3 sideroblasts on BM aspirate smear (greater than 15%) and genetic tests. In the first case, the diagnosis of myelodysplastic syndrome with ring sideroblasts (MDS-RS) with somatic SF3B1 mutation was made at the age of 11 years. A whole exome sequencing did not reveal any germinal predisposition for MDS. A wait-and-see strategy was adopted. After one year- of follow-up, no blood transfusion was needed and no further cytopenia occurred. The two other children had presented anemia at an early age and were diagnosed with CSA. The first case was a girl with SCL25A38 gene mutation. For the second one, the diagnosis of aminolevulinic acid synthase 2 deficiency was considered the most plausible given the family history and the favourable response to pyridoxine. Iron overload occurred in both patients with CSA, requiring chelation therapy. In conclusion, Perls' stain remains a valuable tool for guiding the diagnosis of unexplained anemia in pediatric patients. Genetic testing is crucial for the characterization of congenital sideroblastic anemias. The incidence of myeloid neoplasms with ring sideroblasts is exceptional in children, and the long-term prognosis remains undefined.

This study aims to evaluate the clinical characteristics and biochemical parameters of hemophagocytic lymphohistiocytosis (HLH) patients to predict 30-day mortality. Parameters analyzed include lymphocyte count (L), platelet count (PLT), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), and activated partial thromboplastin time (APTT). Machine learning (ML) approaches, including LASSO, random forest (RF), and support vector machine (SVM), were employed alongside meta-analysis and sensitivity analysis to validate the prognostic potential of these indicators. A retrospective analysis of 151 HLH patients was conducted to identify key predictive variables. Receiver operating characteristic (ROC) analysis, Kaplan-Meier (K-M) survival curves, and Cox regression analysis were used to evaluate the predictive capabilities of these parameters. ML algorithms determined optimal cut-off values to classify patients into high-risk and low-risk groups. A survival nomogram and risk scoring system were developed to provide individualized prognostic assessments. Meta-analysis aggregated data from existing literature to further validate differences in PLT, ALB, and APTT between deceased and surviving patients. Older age, low L, low PLT, low ALB, elevated BUN, and prolonged APTT were strongly associated with higher 30-day mortality risk in HLH patients. Six key indicators-TP, L, APTT, BUN, ALB, and PLT-were identified as critical predictors. ROC and K-M survival analyses highlighted the significance of these parameters. The survival nomogram and risk scoring system demonstrated high accuracy in predicting individualized mortality risk. Meta-analysis confirmed significant differences in PLT, ALB, and APTT between deceased and surviving patients, reinforcing the clinical value of these indicators. This study underscores the prognostic importance of specific clinical and biochemical parameters in predicting 30-day mortality in HLH patients. By integrating ML methodologies, a survival nomogram and risk scoring system were developed, offering valuable tools for early diagnosis, prognosis assessment, and personalized treatment planning in clinical practice.