-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3869 Comparative Analysis of Hematological Parameters in Indian Sickle Cell Anemia Patients Treated with Low Dose (10mg/kg/day) Versus Standard Dose (20mg/kg/day) Hydroxyurea

Program: Oral and Poster Abstracts
Session: 113. Sickle Cell Disease, Sickle Cell Trait and Other Hemoglobinopathies, Excluding Thalassemias: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Sickle Cell Disease, Hemoglobinopathies, Diseases
Monday, December 11, 2023, 6:00 PM-8:00 PM

Naveen Khargekar, MD1*, Manisha Madkaikar2*, Neha Kargutkar3*, Anindita Banerjee4*, Namrata Mahajan1* and Kalpna Gupta, PhD5

1ICMR-National Institute of Immunohaematology, Mumbai, India
2ICMR-National Institute of Immunohaematology, Mumbai, Maharashtra, IND
3ICMR-National Institute of Immunohaematology, Mumbai, AL, IND
4ICMR-National Institute of Immunohaematology, Mumbai, IND
5Hematology/Oncology Division, Department of Medicine, University of California, Irvine, CA

Introduction: Sickle cell anemia (SCA) is a hereditary genetic disorder characterized by the production of abnormal hemoglobin (HbS), which leads to altered physiological properties. Hydroxyurea (HU) is an established oral drug that has demonstrated the ability to ameliorate the severity of the disease mainly by increasing the production of fetal hemoglobin (HbF), thereby reducing sickle cell crises. Studies in the Indian population have shown positive clinical outcomes with a low dose (10 mg/kg/day) of hydroxyurea. Low dose is recommended by most of the physicians in India due to fear of adverse events and noncompliance of patients for regular monitoring of blood parameters. However, the effectiveness of low-dose HU compared to the standard dose (20 mg/kg/day) in reducing sickle cell anemia crises remains uncertain due to the diverse clinical severity of SCD in the Indian population. To address this question, the study aimed to conduct a national level randomized control trial involving SCA patients from various ethnic backgrounds to definitively establish the benefits of low-dose HU for Indian patients compared to the standard dose.

Materials and Methods:

Till date the study enrolled 140 sickle cell anemia patients (2-14 years) after informed consent. Patients were randomly assigned to either low (ARM 1: 10 mg/kg/day) or standard (ARM 2: 20 mg/kg/day) doses of hydroxyurea. 37 patients had been followed up for 6 months’ time point of hydroxyurea therapy. Three ml of whole blood samples were collected in K2-EDTA tube, anthropometric details and clinical parameters of patients were studied.

Results: 18 participants were allotted ARM 1 with a mean age of 8.9 ± 2.8 years and 19 were allotted ARM 2 with a mean age of 8.6 ± 2.5 years. All patients were followed upto 6 months after hydroxyurea treatment. The clinical severity was classified as class 1 and class II based on the clinical events of patients. It was found that 26 patients are classified under the class I category of severity while 10 patients classified under the class II category of severity. 6(60%) participants with baseline HbF level below 15% had Class II severity whereas 3(11.5%) participants with baseline HbF level of more than 15% had Class II severity.

The effect of hydroxyurea dose on haematological indices was also studied which revealed that there was significant decrease in WBC, platelet count by 2.18 ± 2.24 103/µl, 24 ± 136.6 103/µl in ARM 1 compared to ARM II 4.08 ± 2.6 103/µl, 50 ± 127.39 103/µl. A rise in hemoglobin level by 0.18 ± 0.71 gm/dl in ARM I, 0.71 ± 0.77 gm/dl in ARM II and MCV by 3.29 ± 2.61 fl in ARM1, 5.28 ± 3.57 fl in ARM II. The difference was found statistically significant in both the ARMS. (P<0.001). The RBC count in patients did not show a significant elevation in both the ARMS. The absolute neutrophil count in patients were significantly reduced in ARM II by 2874 ± 1748 per µl compared to 1963 ± 1748 per µl in ARM I. Two patients in ARM II showed a reduced ANC level below 1000 thus, hydroxyurea therapy among those two patients was stopped and resumed after a week. Interestingly the rise in HbF was significantly higher in ARM II by 4.81 ± 2.71 % compared to 1.55 ± 2.32 % in ARM I. The critical clinical events such as VOC, Stroke, ACS was not observed in patients at baseline and after 6 months of HU follow up.

Conclusion: The study demonstrated that hydroxyurea treatment in sickle cell anemia patients led to a significant increase in HbF levels in ARM II compared to ARM I. Haematological parameters like WBC Count, platelets, ANC was significantly lower in ARM II with 2(10.5%) of patients in ARM II having ANC below 1000 warranting close monitoring during treatment. Furthermore, the absence of critical clinical events during the 6-month follow-up period suggests the potential benefits of hydroxyurea therapy in managing sickle cell anemia in both ARMS with a long term follow up providing more accurate results to arrive at conclusion.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH