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Sickle cell disease is not so benign

Bone Marrow Transplantation volume 50, page 904 (2015)Cite this article

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Sickle cell disease (SCD) is historically considered to be a benign hemoglobinopathy. There is currently no formal or internationally accepted risk stratification system to determine the long-term outlook for affected individuals. Thus, Rotz et al.1 in their paper took on this important task to modify the current stem cell transplant assessment from a binary yes-or-no checklist of inclusion criteria, into a more quantitative determination based on the clinical presentations. The authors started with two large clinical databases, Cooperative Study of Sickle Cell Disease (CSSCD) and screening and treatment of pulmonary hypertension in sickle cell disease (Walk-PHaSST), and identified several laboratory and clinical parameters associated with increased mortality. They then applied this set of parameters to their contemporary cohort of patients at Case Western Reserve University Hospital (CWRU-UH). At a glance, adults with SCD have low mortality; 3-year mortality in CSSCD was 9.0%, 2-year mortality in Walk-PHaSST was 4.1% and 2-year mortality at CWRU-UH was 2.5%. However, with a closer look at Table 3, one would easily see that several factors singly yielded predictive mortality of near 10% (for example, WBC >13.5 k/μL, brain natriuretic peptide (BNP) >160 pg/L, or lactate dehydrogenase (LDH) >600 units/L). Many two-factor combinations yielded mortality rates >15%. In addition, Figure 2 indicated that as much as 75% of adults with SCD (at CWRU-UH) met the hematopoietic stem cell transplantation (HSCT) criteria from alternative donors.

How are these different rates explained? First, the burden of organ dysfunction is shifting from mainly stroke and spleen dysfunction in children to sickle related nephropathy,2 hepatopathy,3 pulmonary diseases4 and endocrinopathies in adults. The quality of life has been reported to be suboptimal and the morbidity from SCD is significant.5, 6, 7 So while the mortality rate may be relatively low in a short time interval, these rates accumulate over time because the organ damage does not reverse without curative therapy. Hydroxyurea cannot replace transfusions in secondary stroke prophylaxis, and whether it can stabilize organ function or reverse damage is still under investigation. Second, the clinical manifestation of SCD has expanded to incorporate laboratory and other testing results, as seen in this manuscript. These parameters have not redefined the disease—it is still a hemolytic anemia driven by polymerization of sickle hemoglobin tetramers—but they provided robust data sets to estimate morbidity and mortality.8 The authors make this important distinction between morbidity and mortality in their traffic light stratification. During the assessment for transplant, morbidity risk (based mostly on clinical history of vaso-occlusive crisis, acute chest syndrome, stroke and others) is complemented by mortality risk (based on laboratory or testing results): green light, proceed to any transplantation because mortality rate alone exceeds 15%; yellow light, some alternative donor transplantation can be considered in those with intermediate mortality rate OR high morbid conditions; and red light, standard of care transplantation (matched sibling donors) in those with low mortality rate AND moderate morbid conditions.

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References

  1. Rotz SJ, O'Riordan MA, Kim C, Lima M de, Gladwin MT, Little JA . Traffic light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia. Bone Marrow Transplant (e-pub ahead of print 16 March 2015; doi:10.1038/bmt.2015.11.

    Article  CAS  Google Scholar 

  2. Ataga KI, Derebail VK, Archer DR . The glomerulopathy of sickle cell disease. Am J Hematol 2014; 89: 907–914.

    Article  CAS  Google Scholar 

  3. Gardner K, Suddle A, Kane P, O'Grady J, Heaton N, Bomford A et al. How we treat sickle hepatopathy and liver transplantation in adults. Blood 2014; 123: 2302–2307.

    Article  CAS  Google Scholar 

  4. Hamideh D, Alvarez O . Sickle cell disease related mortality in the United States (1999-2009). Pediatr Blood Cancer 2013; 60: 1482–1486.

    Article  Google Scholar 

  5. Swanson ME, Grosse SD, Kulkarni R . Disability among individuals with sickle cell disease: literature review from a public health perspective. Am J Prev Med 2011; 41: S390–S397.

    Article  Google Scholar 

  6. Dickerson AK, Klima J, Rhodes MM, O'Brien SH . Young adults with SCD in US children's hospitals: are they different from adolescents? Pediatr Blood Cancer 2012; 58: 741–745.

    Article  Google Scholar 

  7. Wallen GR, Minniti CP, Krumlauf M, Eckes E, Allen D, Oguhebe A et al. Sleep disturbance, depression and pain in adults with sickle cell disease. BMC Psychiatry 2014; 14: 207.

    Article  Google Scholar 

  8. Sebastiani P, Nolan VG, Baldwin CT, Abad-Grau MM, Wang L, Adewoye AH et al. A network model to predict the risk of death in sickle cell disease. Blood 2007; 110: 2727–2735.

    Article  CAS  Google Scholar 

  9. Lanzkron S, Carroll CP, Haywood C Jr . Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep 2013; 128: 110–116.

    Article  Google Scholar 

  10. Kodish E, Lantos J, Stocking C, Singer PA, Siegler M, Johnson FL . Bone marrow transplantation for sickle cell disease. A study of parents' decisions. N Engl J Med 1991; 325: 1349–1353.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    M M Hsieh

  2. National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    M M Hsieh

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Correspondence to M M Hsieh.

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Hsieh, M. Sickle cell disease is not so benign. Bone Marrow Transplant 50, 904 (2015). https://doi.org/10.1038/bmt.2015.65

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