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2532 Clinical and Laboratory Characteristics of Pediatric Patients with ACKR1/Darc-Associated Neutropenia

Program: Oral and Poster Abstracts
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Hematology Disease Topics & Pathways:
Research, Epidemiology, Clinical Research, Real-world evidence, Treatment Considerations
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Lital Oz-Alcalay, MD1,2*, Orna Steinberg-Shemer, MD3,4*, Sarah Elitzur, MD3,4*, Dafna Brik Simon, MD5,6*, Hannah Tamary, MD7, Shai Izraeli, MD5,8, Joanne Yacobovich, MD, MPH5,9 and Oded Gilad, MD5,9

1Department A, Schneider Children's Medical Center of Israel, Petach Tikva, Israel, Petach Tikva, Israel
2School of Medicine, Tel Aviv University,, Tel Aviv, Israel
3The Rina Zaizov Hematology/Oncology Division, Schneider Children's Medical Center of Israel, Petach Tikva, Israel, Petach Tikva, Israel
4School of Medicine, Tel Aviv University,, Tel Aviv,, Israel
5Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
6Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Tel Aviv, Israel
7Sheba Medical Center, Tel Aviv University, Ramat Gan, Israel
8Department of Pediatric Hematology and Oncology, Schneider Children's Medical Center and Tel Aviv University, Petah Tikva, Israel
9Department of Hematology-Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel

Background: ACKR1/DARC-associated neutropenia (ADAN), resulting from homozygosity for a single nucleotide polymorphism (SNP) in the ACKR1/DARC gene (rs2814778), is a common cause of benign neutropenia that primarily affects individuals of African and Jewish Yemenite descent. We aimed to characterize ADAN in pediatric patients in Israel, given its ethnically diverse population.

Procedure: We assessed children with isolated neutropenia treated during 2018-2023 at one pediatric center, for the ACKR1/DARC polymorphism, using Sanger sequencing or targeted next-generation sequencing.

Results: Of 115 patients evaluated, 55 (47.8%) were diagnosed with ADAN; of these, 27 (49%) were in the severe range (neutrophil count 0-0.5X109/L). The allele distribution revealed 40.0% of Muslim Arab and 58.2% of Jewish origin. The diverse geographical range included Yemenite, Ethiopian, Mediterranean, Asian, and European ancestry. Fifty-one percent had a family history of neutropenia. The median age at the first neutropenia detection was 1.1 years; nearly 90% were identified during routine blood counts. The median absolute neutrophil count at diagnosis was 0.5X109/L (interquartile range 0.3). Patients did not show an increased susceptibility to infections either before or during the median follow-up period of 2.5 years (interquartile range 1.54) after the diagnosis of ADAN. In 42 patients (75.0%), neutrophil counts increased during febrile illnesses.

Conclusions: We identified ADAN in individuals of variable ethnicities, almost half with severe neutropenia. We recommend testing for ADAN in all children with isolated neutropenia without severe infections. This suggests that homozygosity for the ACKR1/DARC rs2814778 SNP eliminates the need for further investigation, follow-up, or treatment in this clinical scenario.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH