scholarly journals P.054 Bone marrow transplant restores Cerebrovascular Reactivity (CVR) in Sickle Cell Disease (SCD): a case presentation

Author(s):  
K Alhadid ◽  
M Kirby-Allen ◽  
G DeVeber ◽  
W Logan ◽  
N Dlamini

Background: A diagnosis of SCD in childhood confers a 200-fold increase in the risk of arterial ischemic stroke. Blood flow velocity measures provide better identification of ischemic risk compared to angiography. This indicates that steno-occlusive arteriopathy is not the singular causative factor. Cerebrovascular reactivity allows for augmentation of cerebral blood flow when needed. Kosinski et al in 2016 demonstrated a direct correlation between CVR and hematocrit levels in SCD. We report a case where CVR persistently normalized in an SCD patient following bone marrow transplant therapy (BMT). Methods: A nine-month-old SCD patient presented with right AIS. Angiography revealed a bilateral Moya-Moya like arteriopathy. A TCD study was normal while a CVR-MRI study revealed markedly impaired reactivity in the entire anterior circulation. Haemaglobin-S at that time was 20.2 %. BMT was performed at age four due to frequent sickle cell crises. Results: One year post-transplant, CVR had dramatically improved in areas previously shown to have impairment (haemoglobin-S 0%). Neuroimaging five years post-transplant showed no further arteriopathy and persistently normalized CVR. Conclusions: BMT therapy resulted in the arrest of progressive intracranial arteriopathy and persistently restored vascular reserve. SCD might not only produce global hematological effects but also triggers local processes such as endothelial dysfunction and vascular inflammation that impair cerebrovascular function.

2002 ◽  
Vol 5 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Morris Kletzel ◽  
Marie Olzewski ◽  
Wei Huang ◽  
Pauline M. Chou

WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis ( n = 45), at relapse ( n = 14), and in remission ( n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis ( n = 14), at relapse ( n = 5), and in remission ( n = 12); and chronic myelogenous leukemia (CML) in blast crisis ( n = 1) and in chronic phase ( n = 1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood ( n = 17), cord blood ( n = 3), and bone marrow ( n = 8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66–0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A930-A931
Author(s):  
Majid Alameri

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.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4466-4466 ◽  
Author(s):  
Pooja Lothe ◽  
Tiffany Pompa ◽  
Maneesh Jain ◽  
Parshva Patel ◽  
Yayu Liang ◽  
...  

Abstract Objective: A comparative cost analysis of sickle cell admissions vs. stem cell transplants in sickle cell patients. Hypothesis: We believe the overall cost of a bone marrow transplant for a sickle cell patient will be less than that of a patient with multiple sickle cell admissions. Background: Sickle cell disease remains an increasing burden to the cost of health care and health care providers. The disease results in a variety of serious organ system complications that can lead to life-long disabilities and/or early death. Despite the advent of hydroxyurea, sickle cell admissions and cost have been increasing over the course of several years. Various contributing factors may include socioeconomic status, complications of sickle cell anemia itself, narcotic dependence and noncompliance with medications. Bone marrow transplants were introduced in 1982 as an option for the treatment of sickle cell anemia, and are currently the only curative option in this disease. A study conducted at the NIH from 2004-2013, found that bone marrow transplant reversed the disease in 26 of 30 patients (87%) (Hseih et al, N Engl J Med 2009; 361:2309-2317). The patients ultimately had a normal hemoglobin, fewer hospitalizations, and lower use of narcotics to treat pain from the disease. However, the underutilization of bone marrow transplant continues to exist and may in part be secondary to a lack of fully matched donors. To overcome this challenge, the Johns Hopkins group developed a nonmyeloablative bone marrow transplantation platform using HLA haploidentical donors for patients using posttransplant cyclophosphamide. As a result, 17 patients were successfully transplanted, 14 from HLA-haploidentical and 3 from HLA-matched related donors (Meade et al, Blood. 2012; 120(22):4285-4291). Due to this, most patients with sickle cell disease have the potential to undergo a successful bone marrow transplant. However, an analysis comparing the cost of admissions vs. transplant has yet to be determined. In order to create an effective cost comparison, we utilized a nationwide database. Methods: US hospital admissions were identified from discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality from 1998 to 2011 using ICD9 codes. Admissions were included if they had an ICD9 code for Sickle cell anemia (282.5). Results: Table 1. Year 1998 1999 2000 2001 2002 2003 2004 Length of Stay (Days) 6.21 6.13 6.37 6.19 6.46 6.31 6.05 Cost ($) 15,724.00 16,465.00 18,654.00 18,750.00 22,587.00 24,501.00 23,743.00 Table 2. Year 2005 2006 2007 2008 2009 2010 2011 Average Length of stay (Days) 6.16 6.13 6.00 5.91 5.62 5.71 5.61 6.04 Cost ($) 25,129.00 27,471.00 28,425.00 27,314.00 29,767.00 29,929.00 31,683.00 24,687.00 The cost per hospitalization has almost doubled since 1998, despite a slight decrease in length of stay from an average of 6.5 days to 5.6 days from 1998-2011. According to the data base from our study, the average cost per patient per hospitalization was $24,687. The average number of admissions per year for a single patient with sickle cell anemia is 6 (Ballas et al, Am J Hem 2009) for an estimated overall cost per year of $148,000. However, this value underestimates the true cost since this does not include emergency room visits, medicine costs, and readmission rates. Conclusion: In the age of cost effective medicine, clinicians struggle to find a balance between low cost and optimal patient care. An underutilized modality of care and even cure for sickle cell disease is bone marrow transplant. The sickle cell information center website estimates the cost of the transplant process for most patients to be $150,000 to $250,000 which includes pre-transplant evaluation, transplant stay, and post-transplant follow-up (https://scinfo.org). We estimate that a bone marrow transplant is approximately equivalent to the cost of ten sickle cell hospital admissions. According to this analysis, undergoing a bone marrow transplant would ultimately prove to be more cost efficient while decreasing the rate of complications associated with this debilitating disease. Disclosures No relevant conflicts of interest to declare.


2000 ◽  
Vol 22 (4) ◽  
pp. 387
Author(s):  
A Woolfrey ◽  
C Hoppe ◽  
R A Nash ◽  
J E Sanders ◽  
E Vichinsky ◽  
...  

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