scholarly journals The Clinical and Radiological Effectiveness of Autologous Bone Marrow Derived Osteoblasts in the Management of Avascular Necrosis of Femoral Head in Sickle Cell Disease.

2021 ◽  
Author(s):  
Mir Sadat-Ali ◽  
Abdallah S Al-Omran ◽  
Sadananda Acharya ◽  
Tarek M Hijazi ◽  
Abid H Gullenpet
Keyword(s):  
Bone Marrow ◽  
Femoral Head ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Joint Arthroplasty ◽  
Long Term Results ◽  
Cell Disease ◽  
Necrosis Of Femoral Head

Abstract Background and Objective: Avascular necrosis of femoral head is a common Issue faced by orthopaedic surgeons which ranges between 10-18% but in sickle cell Disease the incidence reaches 30%. There is no definite treatment except joint arthroplasty. Regenerative medicine is an option to cure or delay joint arthroplasty. We report here our experience with injection of ABMDO to manage ANFH and report our long term results,progression of the ANFH if any and delay in THA (Total Hip Arthoplasty).Patients and Methods: Sixty-Three (63) consecutive patients with SCD with ANFH were examined, thoroughly investigated and those who had ANFH < grade II were consented to receive ABMDO. Pre-operatively patients were clinically assessed using Visual analogue scale (VAS), Modified Harris Hips Score (MHHS) and Azam-Sadat Score (ASS) for Quality of Life Score for Chronic Hip Disease. Ten milliliter of bone marrow was aspirated under local anesthesia and was placed in 20 CC culture media. Osteoblasts were cultured from the bone marrow aspirated. Under anesthesia using 3 mm cannulated drill, the osteonecrosed lesion was drilled and 5 million osteoblasts were injected at the lesion site. Patients were evaluated in out patient clinic after two weeks. At four months a repeat MRI was done and patients were followed up a minimum for 2 years.Results: The average age was 25.93±5.48 years. There were 41 (65%) females and 22 (35%) males. The mean hemoglobin S was 83.2±5.1 percent. The average follow up was 49.05±12.9 ( range 24-60) months. VAS significantly improved from 7.79±1.06 at 2 weeks 4.07±1.08 p<0.0001 continued to improve for the next 24 months 2.38±0.55 (P<0.0001). MHHS improved from 41.77±5.37 to 73.19± 6.48 at 4 months (P<0.001) and at 24 months it was 88.93±3.6 (p<0.001). The ASS also significantly improved from 2.76±0.49 preoperatively to 7.92±0.09 (p<0.0001) at 24 months. A comparison of the MRI’s of before and after osteoblast implantation revealed new bone formation and amelioration of the avascular lesions. Three patients were unhappy with the outcome and one patients repeated attacks of the vaso-occlusive crisis within six months of the osteoblasts injection.Conclusions: The results give credence to our earlier short follow up results that osteoblasts transplantation has a great potential in healing of avascular lesions. Our study fits the criteria of Phase II clinical trial and We believe a larger study equivalent to Phase III numbers and include patients not only with sickle cell disease but also steroid induced and idiopathic avascular necrosis.

scholarly journals Spontaneous healing of avascular necrosis of the femoral head in sickle cell disease

2019 ◽  
Vol 94 (6) ◽  
pp. E160-E162 ◽  
Author(s):  
Nelda P. Itzep ◽  
Siddharth P. Jadhav ◽  
Celeste K. Kanne ◽  
Vivien A. Sheehan
Keyword(s):  
Femoral Head ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Cell Disease ◽  
Spontaneous Healing

Hydroxyurea Use Is Associated with Avascular Necrosis of the Femoral Head among Children with Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2477-2477 ◽  
Author(s):  
Kris Michael Mahadeo ◽  
Suzette Oyeku ◽  
Karen Moody ◽  
Swapmil N. Rajpathak ◽  
Abraham Groner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Femoral Head ◽  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Odds Ratio ◽  
Demographic Characteristics ◽  
Cell Disease ◽  
Health Maintenance ◽  
Laboratory Values

Abstract Hydroxyurea therapy is associated with reduced morbidity among patients with sickle cell disease (SCD). Avascular necrosis of the femoral head (AVN) is one potentially debilitating complication of SCD. In this study, we examined the relationship between hydroxyurea use and the prevalence of AVN among children with SCD. We performed a retrospective chart review of 202 children with SCD, aged 10–21 years, followed in the pediatric hematology program at the Children’s Hospital at Montefiore (Bronx, NY) between July 2007 and 2008. Abstracted data included age, ethnicity, SCD genotype, frequency of hospitalization, hip radiograph results, laboratory data and hydroxyurea use. Hip radiographs were performed prospectively as part of SCD health maintenance from 2005–2008. Forty-four patients were excluded because they did not have a screening hip radiograph. Descriptive statistics were calculated for independent variables. T-tests and chi-square tests were used to compare clinical and demographic characteristics of children with and without AVN. Multivariate logistic regressions were used to estimate the odds ratio of having AVN among SCD patients. Our final sample consisted of 158 patients whose demographic characteristics are listed in Table 1. The prevalence of AVN was 16.5% (n=26). Of the clinical variables analyzed, we identified significant associations between the presence of AVN and hydroxyurea use (p=.005), as well as older age (p=.013) (Table 1.) Children with AVN had significantly lower mean lactic dehydrogenase levels (LDH) (p=.04) and higher mean corpuscular volumes (MCV) (p=.012). (Table 2.) After controlling for gender, ethnicity, sickle cell genotype, and frequency of hospitalizations, age was also found to be associated with AVN (OR 1.15, 95% confidence interval (CI): 1.01,1.31, p=0.033). SCD patients on hydroxyurea had higher odds of having AVN compared to non-users (OR 3.51, 95% CI: 1.31, 9.38, p= 0.013). Laboratory values (MCV, Hemoglobin, LDH and Hematocrit) had a high degree of collinearity and were removed from the final model. In summary, the prevalence of AVN in our sample was 16.5%. This is substantially higher than the prevalence of approximately 6% reported by the Cooperative Study of Sickle Cell Disease for comparative age groups in a prospective study1. SCD patients exposed to hydroxyurea were three times more likely to have AVN than those not exposed to this drug. Vaso-occlusive pain crisis is a recognized risk factor for AVN, thus we could expect a higher rate of AVN among patients on hydroxyurea. However, the odds ratio of 3.5 is unexpectedly high and warrants further investigation into the role of hydroxyurea as a risk factor for AVN. Nonetheless, these preliminary results suggest that more stringent screening regimens for AVN may be indicated among this subset of patients. Table 1. Clinical characteristics of patients with and without avn *p&lt;0.05 **p&lt;0.01 No AVN (N =132) AVN (N = 26) Age * 15.7 years 17.4 years Sex Male 64 (49%) 17 (65%) Ethnicity Black 110 (83%) 23 (88%) Hispanic 22 (17%) 3 (12%) HgbSS 84 (64%) 20 (77%) HgbSC 38 (29%) 4 (15%) HgbSBthal0 5(3.8%) 2 (8%) Hgb SC HgbSBthal+ 5 (3.8%) 0 On Hydroxyurea** 38 (29%) 15 (58%) # Hospitalizations 0 60 (45%) 10 (38%) 1–5 64 (49%) 14 (54%) &gt;5 8 (6%) 2 (8%) Table 2. Mean Laboratory Values for Patients With And Without AVN No AVN AVN *p&lt;0.05 (N =132) (N = 26) WBC 10.7 k/uL 10.5 k/uL Hgb 9.4 gm/dL 9.6 gm/dL MCV* 83 fL 89 fL Platelets 381 k/uL 376 k/uL Reticulocyte 7.70% 8.10% Ferritin 369.8 ng/mL 438.7 ng/mL LDH* 471.6 U/L 389 U/L Creatinine 0.6 mg/dL 0.6 mg/dL Hgb F 9.80% 11.30%

Hematopoietic Stem Cell Transplantation for Sickle Cell Disease in Childhood: A Single Center Experience with 45 Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3103-3103 ◽  
Author(s):  
Laurence Dedeken ◽  
Phu-Quoc Le ◽  
Nadira Azzi ◽  
Cecile Brachet ◽  
Catherine Heijmans ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Sickle Cell ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract Abstract 3103 Despite improvement in medical management, sickle cell disease (SCD) is still associated with high risk of morbidity, chronic disability and early death. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative approach. Since November 1988, 45 patients (median age: 8.3 years; range: 1.7–15.3 years) with severe SCD underwent related HSCT in our unit. Thirty-five received bone marrow transplant, 3 cord blood, 6 bone marrow and cord blood and 1 peripheral blood stem cells. Two donors result from preimplantation genetic diagnosis with HLA selection. All were HLA-identical sibling except one who had one class II mismatch. All had one or more severe manifestations: 24 patients presented more than 2 vaso-occlusive crises per year, 11 recurrent acute chest syndrome, 19 cerebral vasculopathy and 4 erythroid alloimmunisation. Conditioning regimen consisted of the standard combination of busulfan, cyclophosphamide and from November 1991 antithymocyte globulins (ATG) were added: ATG Fresenius first and from July 2000 ATG Merieux. Since 1995 all patients were treated with hydroxyurea (HU) prior to transplantation for a median duration of 2.7 years (range: 0.8–10.7 years). Acute graft versus host disease (GVHD) was observed in 11 patients (3 grade III and 2 grade IV). Ten patients were treated for CMV reactivation and 4 for EBV reactivation. Only one patient had presented a probable invasive fungal disease. After median follow-up of 6.5 years, 10 patients had presented chronic GVHD, none was extensive. Only one required therapy beyond 2 years from transplant. Engraftment was successful in 42/45. One rejection occurred 15 months after transplantation. Since HU introduction before transplant (1995), no graft failure occurred. Important mixed chimerism is present in 2 patients (AA donor) who remain free of any sickle cell disease symptoms. Two deaths occurred: 1 unexplained death 6 years after HSCT in a child free of any treatment and 1 cerebral hemorrhage 18 days after transplant in a child with severe cerebral vasculopathy. Growth was normal after transplant. As expected, gonadal function was impaired in the majority of girls. However 3 girls had spontaneous normal puberty and one had two spontaneous pregnancies with normal outcome. Our results are very encouraging showing excellent outcomes. Both the overall survival (OS: 95.6%) and the event-free survival (EFS: 86.7%) are comparable to the other published studies, ranging from 93 to 97%, and 82 to 86 % respectively. Since 1995, all the 33 patients engrafted successfully. Previous treatment with HU may have contributed to successful engraftment. After 5.3 years of follow-up, their OS and EFS are both at 96.9%. The difference in outcome before and after 1995 is strongly significant for EFS (58.3% vs 96.9%, p=0.003). Severe cerebral vasculopathy with its risk of CNS hemorrhage remains a true challenge. Disclosures: No relevant conflicts of interest to declare.

A North American Experience Of Hemoglobin SC Disease, Its Complications, and Management

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2221-2221 ◽  
Author(s):  
Veronique Naessens ◽  
Richard Ward ◽  
Kevin H.M. Kuo
Keyword(s):  
Sickle Cell Disease ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Care Center ◽  
Comprehensive Care ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Baseline Hemoglobin ◽  
Hemoglobin Sc Disease

Background The phenotype of hemoglobin SC (HbSC) disease is distinct from sickle cell anemia (SCA) (HbSS and S/b0) but management of adults is mostly derived from studies of the latter group. Longitudinal observational studies on the complications and outcomes of hemoglobin SC disease are largely confined to centers outside North America. The unique ethnic composition of our cohort, consisting of mostly Western Africans and West Indians, permits further characterization of the HbSC phenotype. Objective to describe the baseline characteristics and long-term complications of a cohort of adult HbSC patients followed in a Canadian sickle cell comprehensive care center. Methods A retrospective observational cohort study was conducted on all adult patients with HbSC disease attending a sickle cell comprehensive care center in Toronto, Canada from 1994 to 2013. Baseline demographics, acute and chronic complications attributable to sickle cell disease, and laboratory data were collected. Medians were used to describe continuous variables, while percentages or ratios for categorical variables. Logistic regression was used to examine factors influencing the main clinical complications. Results 104 patients were included in the analysis, comprising of 38.5% males and 61.5% females. Median length of follow-up was 3.5 years (1 - 19) and median age at last recorded visit was 35 years (18 - 68). Median baseline hemoglobin was 119 g/L (82 - 153 g/L), hematocrit 0.340 (0.250 - 0.440), and fetal hemoglobin (HbF) fraction 1% (0 - 7.7%). Most frequent complications encountered were retinopathy (55.8%) and symptomatic avascular necrosis (27.9%), followed by painful vaso-occlusive crises requiring emergency room visit (23.1%). Presence of retinopathy was associated with higher baseline hemoglobin (OR 2.72 for every 10 g/L of hemoglobin, p = 0.037) and older age (OR 2.72 for every decade, p < 0.001). Acute chest syndrome (7.7%), priapism (7.5% of men), and renal involvement (8.2%), were less common than reported in the literature, while the rates of venous thromboembolism (8.7%), symptomatic infarctive or hemorrhagic stroke (2.9%) were slightly more common. Median right ventricular systolic pressure on 2D-transthoracic echocardiogram was 29 mmHg (17 – 43 mmHg). No patient underwent a right heart catheterization. Two patients died from septic shock, both at the age of 29. Disease-modifying therapy most often consisted of hydroxyurea (28.8%), followed by exchange transfusion (6.7%) and phlebotomies (5.8%). Hydroxyurea significantly increased the median HbF fraction (from 1% to 2.75%, p = 0.004 by related-samples Wilcoxon signed rank test). Conclusion In this large North American cohort of adult patients, we have again shown that HbSC disease is not as benign as traditionally thought. As such, patients with HbSC disease warrant similar follow-up to that provided to SCA. Retinopathy, avascular necrosis and painful vaso-occlusive crises were the most common complications in our study, albeit lower than in other reported cohorts. The frequent use of hydroxyurea in this cohort is quite unique compared to other sickle cell comprehensive care centers reported in the literature. However, therapeutic phlebotomy is less often used compared to the European experience. We also observed a lower frequency of retinopathy, avascular necrosis, painful vaso-occlusive crises, priapism and acute chest syndrome. Whether this observation is due to hydroxyurea use or to other genetic or environmental factors remains to be determined. Further studies are also required to develop a more evidence-based therapeutic strategy for this genotype of Sickle Cell Disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Management of osteonecrosis of the femoral head in children with sickle cell disease: results of conservative and operative treatments at skeletal maturity

2018 ◽  
Vol 12 (1) ◽  
pp. 47-54
Author(s):  
C. Mallet ◽  
A. Abitan ◽  
C. Vidal ◽  
L. Holvoet ◽  
K. Mazda ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Femoral Head ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Skeletal Maturity ◽  
Weight Bearing ◽  
Long Term Results ◽  
Harris Hip Score ◽  
Cell Disease ◽  
Femoral Head Osteonecrosis

Purpose Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. Methods All children with ONFH due to SCD were retrospectively reviewed. At initial evaluation, extension of osteonecrosis was radiographically defined using Catterall, lateral pillar Herring and Ficat classifications. Subluxation of the femoral head with Reimers migration index > 30% required surgical treatment including femoral varus osteotomy and/or pelvic osteotomies. Conservative treatment including non-weight bearing and physiotherapy was performed in the remaining cases. Outcomes were assessed at skeletal maturity using the Harris Hip Score (HHS) and the Stulberg classification. Total hip arthroplasty and Stulberg 5 were defined as failures. Results A total of 25 hips in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall 3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4. Conclusion Both treatments led to good functional results with 75% of congruent hips at skeletal maturity. Level of Evidence IV

scholarly journals Graves’ Disease After Hematopoietic Allogeneic Bone Marrow Transplant in a Patient With Sickle Cell Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A930-A931
Author(s):  
Majid Alameri
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Marrow Transplant ◽  
Graves Disease ◽  
Allogeneic Bone ◽  
Cell Disease ◽  
Free T4 ◽  
Post Transplant

Abstract Endocrinopathies are among the most recognized late complications post hematopoietic stem cell transplant (HSCT). Dysfunctions of hormonal axes including the hypothalamus, pituitary, gonads, thyroid and adrenals reported. Moreover, thyroid dysfunctions including thyroiditis, hypothyroidism and hyperthyroidism has been reported to develop 8-32 months after HSCT. We report a 27-year-old male with sickle cell disease diagnosed at age of 5. He had multiple painful vasoocclusive sickle crises treated with blood transfusions, folic acid and rituximab. At age of 21, he presented with sudden right sided weakness and slurred speech. Further investigations, including magnetic resonance imaging of brain revealed occlusion of the left middle cerebral artery resulting in ischemic infarction. Subsequently, he had multiple red blood cell exchange transfusions on regular basis. He remained with residual weakness and slurred speech after rehabilitation. Bone marrow transplant was recommended as a curative treatment for his sickle cell disease by haematology team. A year later, he underwent a geno-identical allogeneic bone marrow transplantation harvested from his brother. He remained well for 22 months post-transplant without any evidence of graft versus host disease. 23 months post-transplant, he presented with loose motions, 2 kg wight loss and fine tremors. He was referred to endocrine department for further workup. Physical examination revealed a small smooth goitre. He had discrete exophthalmos of his left eye without any signs of active inflammation. Thyroid function tests confirmed diagnosis of Graves’ disease with TSH&lt;0.01 milli IU/L, Free T4=23.9 pmol/L, and TSH receptor antibodies of 3.79 IU/ml. Ophthalmological consultation suggested 6 months of selenium supplementation (200 mcg/day) with regular follow up. There has been no family history of autoimmune diseases or thyroid disorders. He started carbimazole (CMZ) 30 mg daily. His symptoms improved within 8 weeks, with normalization of Free T4 and Free T3 (TSH remained suppressed). 18 months later, he remained asymptomatic on carbimazole. He had recurrence of hyperthyroidism symptoms after 4 weeks trail of stopping carbimazole with elevation of Free T4 and Free T3. Carbimazole was restarted and he has been offered other treatment modalities of Graves’ disease. He elected to undergo total thyroidectomy. His sickle cell and blood counts remained stable during follow up period. Conclusion: Transplanted patients carries a life-long risk for developing endocrinopathies post initial transplant therapy. Acknowledging the wide spectrum of post-transplant endocrinopathies, an individualized case based periodic screening can be helpful to improve health outcomes of such patients. Because of the usual late presentation of such endocrine complications, transplanted patients might need life-long endocrine follow-up.

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