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2187 Hydroxyurea Shows Clinical Benefit without Alteration of Fetal Hemoglobin, MCV, or Hemoglobin in Unselected Adult and Pediatric Patients with Sickle Cell Anemia

Hemoglobinopathies, Excluding Thalassemia – Clinical
Program: Oral and Poster Abstracts
Session: 114. Hemoglobinopathies, Excluding Thalassemia – Clinical: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Crawford John Strunk, MD1, Biree Andemariam, M.D.2, Fredericka Sey, MB ChB3*, Fatimah Farooq, BS4*, Rebekah Urbonya, BS4*, Charles Antwi-Boasiako, Ph.D5*, Adetola A. Kassim, MD, MS6, Onike Rodrigues, MD7*, Connie M. Piccone, MD8, Angela Rivers, MD, PhD9, Deepa Manwani, MD10, Imma Tartaglione, MD11*, Laura Sainati, MD12*, Raffaella Colombatti, MD, PhD13* and Andrew D. Campbell, MD14

1ProMedica Toledo Children’s Hospital, Toledo, OH
2Hematology, University of Connecticut Health Center, Farmington, CT
3Ghana Institute of Clinical Genetics, Ministry of Health, Ghana. Korle Bu Teaching Hospital, Accra, Ghana
4Division of Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI
5Department of Physiology, University of Ghana Medical School, Accra, Ghana
6Vanderbilt University School of Medicine, Nashville, TN
7Dept. of Child Health, University of Ghana Medical School, Accra, Ghana
8Case Western Reserve University, Cleveland, OH
9Department of Pediatrics, University of Illinois at Chicago, Jesse Brown VA Medical Center, Chicago, IL
10Department of Pediatrics, Albert Einstein College of Medicine, Children's Hospital at Montefiore, Bronx, NY
116I°Policlinico II°Università di Napoli,, Naples, Italy;, Italy
12University of Padua, Department of Women’s and Chidren’s Health, Italy, University of Padua, Padua, Italy
13Azienda Ospedaliera - Università di Padova, Clinic of Pediatric Hematology Oncology, Department of Pediatrics,, Padova, Italy
14Pediatric Hematology/Oncology, Univ. of Michigan Med. Ctr., Ann Arbor, MI

Introduction

Sickle cell anemia is the most common single gene defect in the United States, affecting approximately 100,000 individuals (Hassel Am J Prev Med 2010).  It is characterized by chronic hemolysis, unpredictable vaso-occlusive episodes (VOEs), and chronic organ damage leading to early death in patients affected by the disorder.  Hydroxyurea, a small molecule chemotherapeutic agent, has been used to treat patients with severe sickle cell disease since 1984 (Brawley Ann Intern Med 2008).  Two randomized controlled trials, the Multicenter Study of Hydroxyurea (Charache N Engl J Med 1995) in adults and the Baby HUG trial (Wang Lancet 2011) in children, showed that hydroxyurea reduced the number of VOEs and hospital admissions, while simultaneously increasing hemoglobin and fetal hemoglobin in patients with sickle cell anemia.  The goal of this study was to determine the clinical effectiveness of hydroxyurea in reducing the number VOEs and hospitalizations in unselected patients with sickle cell anemia.

Methods

The CASIRE group is an international multi-institutional collaborative group evaluating the clinical severity of patients with sickle cell anemia through a validated questionnaire, chart review and laboratory studies.  Patients were enrolled on the CASIRE study after informed consent and assent was obtained from either the parent or patient when appropriate.  The study was approved at each participating institution’s IRB.  A questionnaire was answered by the parents and/or patient, and baseline and current laboratory studies were collected.  Patients were stratified into those who were not on hydroxyurea, and those who were currently on hydroxyurea.  Number of VOEs, admissions, baseline and current fetal hemoglobin, and change in hemoglobin and MCV were compared.

Results

There were 349 patients in this study (134 on hydroxyurea).  Baseline laboratory data are reported in table 1.  Hemoglobin level and MCV were not statistically different in patients prior to and after taking hydroxyurea (table 2).  Fetal hemoglobin in adults increased 2.7 times baseline, whereas in children it was unchanged.  All patients on hydroxyurea had a reduction of VOEs, ED visits and admissions compared to prior to hydroxyurea (see table 3).

Table 1 Baseline laboratory data

Baseline data

Patients on Hydroxyurea

Patients not on Hydroxyurea

 

Pediatric

Adult

Pediatric

Adult

N

78

56

140

75

Age

10

26.9

8.6

28.3

Hemoglobin (g/dL)

8.7

9.7

9.39

9.4

MCV (fL)

91

91.5

79

86

Fetal Hemoglobin (%)

15.1

12.4

9.6

5

Table 2. Clinical data for patients on HU

 

                           Patients on Hydroxyurea

 

Pediatric (78)

Adult (56)

Dose of HU (mg/kg)

23.8

20.5

# doses missed/wk

1

1.55

Fetal Hemoglobin on HU (%)

14.5

13.8

D MCV from baseline (fL)

+5.4

+0.1

D Hgb from baseline (g/dL)

+0.23

+0.4

Table 3. Number of pain episodes in patients on HU.

 

Prior to HU

In last year on HU

2 tailed paired t test

Pediatric patients (N = 78)

 

 

 

          # pain episodes/year

25

12.9

0.62

          # requiring ED/year

2.66

1

0.93

          # requiring admission/year

4.28

1.79

0.017

Adult patients (N = 56)

 

 

 

          # pain episodes/year

36.7

28.6

0.021

          # requiring ED/year

5.7

2.4

0

          # requiring admission/year

6.6

3.15

0.117

Conclusion

The Multicenter Study of Hydroxyurea and the BABY HUG study showed that hydroxyurea is efficacious for patients with sickle cell anemia.  No previous study has evaluated the effectiveness of hydroxyurea in clinical practice.  Our study suggests that, although baseline and current laboratory values are similar in patients prior to versus after taking hydroxyurea, there was a clear reduction in the number of VOEs and admissions, similar to the Baby HUG and MSH studies.  These results suggest that the reduction of VOEs could be the product of a generalized decrease in overall inflammation and hemolysis or increased nitric oxide production rather than an increase in fetal hemoglobin by itself.  Reasons for the similarity in laboratory values could include the length of time patients have been on hydroxyurea or that hydroxyurea was not escalated to maximum tolerated dose.  Another reason may be the degree of compliance of patients in a clinical setting.  We noted that 1/3 of our pediatric and ½ of our adult patients missed at least 1 dose of hydroxyurea per week suggesting that even partial compliance with hydroxyurea may prove beneficial clinically.  This study demonstrates that hydroxyurea is effective in reducing the number of VOEs and admissions for unselected patients with sickle cell anemia.

Disclosures: Colombatti: Eli Lilly and Company: Research Funding .

*signifies non-member of ASH