Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia.

Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age> or =12 years and liver iron concentration> or =10 mg/g dry wt or serum ferritin> or =2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin<500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6+/-0.7 years), 203 subjects with TxSCD (44% Male, 24.7+/-0.9 years: Mean+/-SE), and 65 NonTxSCD (50% Male, 22.2+/-1.3 years) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p=0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

Physical therapy alone compared with core decompression and physical therapy for femoral head osteonecrosis in sickle cell disease. Results of a multicenter study at a mean of three years after treatment.

BACKGROUND: Osteonecrosis of the femoral head is a common complication in patients with sickle cell disease, and collapse of the femoral head occurs in 90% of patients within five years after the diagnosis of the osteonecrosis. However, the efficacy of hip core decompression to prevent the progression of osteonecrosis in these patients is still controversial. METHODS: In a prospective multicenter study, we evaluated the safety of hip core decompression and compared the results of decompression and physical therapy with those of physical therapy alone for the treatment of osteonecrosis of the femoral head in patients with sickle cell disease. Forty-six patients (forty-six hips) with sickle cell disease and Steinberg Stage-I, II, or III osteonecrosis of the femoral head were randomized to one of two treatment arms: (1) hip core decompression followed by a physical therapy program or (2) a physical therapy program alone. Eight patients withdrew from the study, leaving thirty-eight who participated. RESULTS: Seventeen patients (seventeen hips) underwent decompression combined with physical therapy, and no intraoperative or immediate postoperative complications occurred. Twenty-one patients (twenty-one hips) were treated with physical therapy alone. After a mean of three years, the hip survival rate was 82% in the group treated with decompression and physical therapy and 86% in the group treated with physical therapy alone. According to a modification of the Harris hip score, the mean clinical improvement was 18.1 points for the patients treated with hip core decompression and physical therapy compared with 15.7 points for those treated with physical therapy alone. With the numbers studied, the differences were not significant. CONCLUSIONS: In this randomized prospective study, physical therapy alone appeared to be as effective as hip core decompression followed by physical therapy in improving hip function and postponing the need for additional surgical intervention at a mean of three years after treatment.

Sibling donor cord blood transplantation for thalassemia major: Experience of the Sibling Donor Cord Blood Program.

The Sibling Donor Cord Blood (SDCB) Program was initiated in 1998 as a resource to collect, characterize, and release cord blood units (CBUs) from families affected by malignant and nonmalignant disorders for transplantation. Families in the United States were recruited by telephone after referrals by community and academic physicians. Collection kits were mailed to prospective participants and family members were instructed about CBU procurement from community hospitals and shipping to a central laboratory. Data about the infant's delivery and CBU harvest, CBU processing, prethaw characteristics, sterility, and human leukocyte antigen (HLA) typing were collected. Standard outcome data were collected after CBU release for transplantation. Descriptive analyses of CBU collections, processing, release, and transplantation outcomes were performed. Currently, 1617 CBU collections have been processed from families with thalassemia (6%), sickle cell disease (28%), malignant disorders (49%), and other rare hematological disorders (17%). Thirty-two of 96 donor-recipient pairs with thalassemia major were HLA identical and 14 have received cord blood transplantation, either alone or in combination with bone marrow or peripheral blood progenitor cells (N = 4) from the same donor. Eleven of the 14 survive free of thalassemia after transplantation. These preliminary results confirm the feasibility and utility of remote-site sibling donor cord blood collection and subsequent transplantation for hematological disorders, with a very high rate of usage from a cord blood bank dedicated to performing these unique collections. It was concluded that cord blood transplantation from sibling donors represents a suitable alternative to bone marrow transplantation.

Clinical evaluation of avascular necrosis in patients with sickle cell disease: Children's Hospital Oakland Hip Evaluation Scale--a modification of the Harris Hip Score.

OBJECTIVE: To establish the validity and reliability of the Children's Hospital Oakland Hip Evaluation Scale (CHOHES), a modification of the Harris Hip Score, for the evaluation of avascular necrosis (AVN) in sickle cell disease (SCD). DESIGN: Nonrandomized test-retest. SETTING: Outpatient clinic. PARTICIPANTS: Forty patients with SCD and 3 healthy controls participated. Twenty-six SCD patients (15 males, 11 females; mean age, 25 y) had been diagnosed with AVN. This group was compared with 14 SCD patients without AVN and 3 healthy controls (8 males, 9 females; mean age, 16 y). INTERVENTION: On average, subjects were assessed by 2 physical therapists by using the CHOHES on 3 separate outpatient visits within a 2-week period. MAIN OUTCOME MEASURES: A mixed model with random effects was constructed to compare patient scores on the CHOHES with disease severity as estimated by Ficat staging on plain radiographs. Correlations between and within physical therapists using the CHOHES were calculated to assess intra- and interrater reliability. RESULTS: From the random effects model, the CHOHES mean score was 88 for Ficat stage 0, 75 for Ficat stage I or II, and 61 for Ficat stages III or IV (P < .05). Intrarater reliability estimates for the total CHOHES score were very good (r > or = .87) as were interrater reliability estimates (r > or = .90) between therapists who measured hips with a wide range of CHOHES scores. CONCLUSIONS: The CHOHES appears to be an easy-to-use, valid, and reliable assessment tool and should be considered for use in the routine clinical evaluation of SCD patients with AVN.

Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease.

UNLABELLED: PURPOSE Few studies address the association of Chlamydia pneumoniae infection with pulmonary disease and outcome in patients with underlying pathology such as sickle cell disease (SCD). SCD patients are susceptible to the pulmonary disorder known as acute chest syndrome (ACS), where the etiology remains ill defined. The purpose of this study was to analyze the clinical course and outcome of C. pneumoniae-associated ACS among SCD patients as part of the National Acute Chest Syndrome Study. PATIENTS AND METHODS: This was a longitudinal study of SCD patients presenting with ACS to multiple U.S. medical centers. Two hundred ninety-six SCD patients who developed ACS were tested by PCR for C. pneumoniae and by standard techniques for other respiratory pathogens. These infections were evaluated for association with ACS, clinical course, and complications. RESULTS: Forty-one (14%) patients with first episodes of ACS were PCR positive for C. pneumoniae. Compared with other infections, C. pneumoniae-infected patients were older, were more likely to present with chest pain, and had higher hemoglobin levels at diagnosis. Both groups had similar rates of respiratory failure and prolonged hospitalization. Of the 89 patients with single-pathogen infections, 27 (30%) were due to C. pneumoniae, 21% to Mycoplasma pneumoniae, 10% to RSV, 4% to Staphylococcus aureus, and 3% to Streptococcus pneumoniae. CONCLUSIONS: C. pneumoniae was the most prevalent pathogen in this study of ACS and was responsible for significant morbidity. Additional research is required to develop effective treatment guidelines for ACS.