Luspatercept, a two-edged sword in beta-thalassemia-associated paravertebral extramedullary hematopoietic masses (EHMs).

Paravertebral extramedullary hematopoietic masses (EHMs) account for up to 15% of extramedullary pseudotumors in beta-thalassemia (BT) and are most likely related to compensatory hematopoiesis. In most cases, pseudotumors are incidentally detected, as the majority of patients are asymptomatic. Since June 2020, luspatercept is approved for the treatment of patients with BT who require regular red blood cell transfusions. Data addressing the safety and efficacy of luspatercept in patients with BT-associated EHMs are pending. To date (May 2022), paravertebral EHMs were observed in two asymptomatic patients out of currently 43 adult patients with BT registered at the Adult Hemoglobinopathy Outpatient Unit of the University Hospital Essen, Germany. In one of them, a paravertebral EHM was diagnosed more than 10 years prior to referral. Throughout observation time, treatment with luspatercept was associated with a clinically significant reduction in transfusion burden while allowing to maintain a baseline hemoglobin concentration of ≥10 g/dL aiming to suppress endogenous (ineffective) erythropoiesis associated with BT. Considering the rarity of paravertebral EHMs in BT, luspatercept might potentially represent a novel therapeutic option for these often-serious disease-associated complications. However, appropriate follow-up investigations are recommended to detect (early) treatment failures secondary to an undesired luspatercept-associated erythroid expansion.

Screening and diagnosis of hemoglobinopathies in Germany: Current state and future perspectives.

This monocentric study conducted at the Pediatric and Adult Hemoglobinopathy Outpatient Units of the University Hospital of Essen summarizes the results of hemoglobinopathies diagnosed between August 2018 and September 2021, prior to the introduction of a general newborn screening (NBS) for SCD in Germany (October 2021). In total, 339 patients (pts.), 182 pediatric [50.5% males (92/182)] and 157 adult pts. [75.8% females (119/157)] were diagnosed by molecular analysis. The most common (parental) descent among affected pts. were the Middle Eastern and North African/Turkey (Turkey: 19.8%, Syria: 11.8%, and Iraq: 5.9%), and the sub-Saharan African region (21.3%). Median age at diagnosis in pediatric carriers [N = 157; 54.1% males (85/157)] was 6.2 yrs. (range 1 (months) mos.-17.8 yrs.) and 31 yrs. (range 18-65 yrs.) in adults [N = 53; 75.2% females (115/153)]. Median age at diagnosis of homozygous or compound-heterozygous disease in pediatric pts. (72% (18/25) females) was 3.7 yrs., range 4 mos.-17 yrs. (HbSS (N = 13): 2.5 yrs., range 5 mos.-7.8 yrs.; HbS/C disease (N = 5): 8 yrs., range 1-8 yrs.; homozygous/compound heterozygous ß-thalassemia (N = 5): 8 yrs., range 3-13 yrs.), in contrast to HbH disease (N = 5): 18 yrs. (median), range 12-40 yrs. Hemoglobinopathies represent a relevant health problem in Germany due to immigration and late diagnosis of second/third generation migrants. SCD-NBS will accelerate diagnosis and might result in reduction of disease-associated morbidity. However, diagnosis of carriers and/or disease-states (i.e. thalassemic syndromes) in newly immigrated and undiagnosed patients will further be delayed. A first major step has been taken, but further steps are required.

Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

BACKGROUND: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. METHODS/RESULTS: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. CONCLUSION: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.