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Inherited and Genetic Disorders

Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia

Bone Marrow Transplantation volume 50, pages 918–923 (2015)Cite this article

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Abstract

Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and UK). Parallel investigations were also undertaken in the Cooperative Study of Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease population (Case Western Reserve University-University Hospitals (CWRU-UH), Cleveland, OH, USA). One- and two-value positive predictive values for 2-year mortality (from study entry) are calculated using factors that include demographics, laboratory values and clinical evaluations. We define high-, intermediate-, and low-risk SCA as >15%, 10–15% and <10% 2-year mortality. In walk-PHaSST, no single factor qualifies as high-risk SCA, although several combinations of two factors (that is, both age >35 years and history of chronic transfusion) do. Either elevated white blood cell count (>13.5 × 103 cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (⩾3.0 m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as were many two-factor combinations. N-terminal pro-brain natriuretic peptide >160 ng/L, lactate dehydrogenase >600 IU/L, history of chronic transfusion, sepsis or age >35 years are individually associated with low-risk SCA, as are many two-factor combinations. SCA risk was integrated with estimated donor type-associated risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials of HSCT. This method is adaptable to evolutions in clinical care.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Case Western Reserve University, University Hospitals, Cleveland, OH, USA

    S J Rotz, C Kim, M de Lima & J A Little

  2. Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, OH, USA

    S J Rotz & M A O'Riordan

  3. Division of Pulmonary, Allergy, Critical Care Medicine-Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA

    M T Gladwin

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  1. S J Rotz
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Correspondence to J A Little.

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Competing interests

Dr Gladwin reports the following conflict of interest. Bayer Pharma AG: consultancy and research funding; US Government: co-inventor on a provisional patent for nitrite salts for cardiovascular indications. The other authors declare no conflict of interest.

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Rotz, S., O'Riordan, M., Kim, C. et al. Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia. Bone Marrow Transplant 50, 918–923 (2015). https://doi.org/10.1038/bmt.2015.11

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  • DOI: https://doi.org/10.1038/bmt.2015.11

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