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JAMA. 2019 Jan 22;321(3):266-276. doi: 10.1001/jama.2018.20059.

Association of Matched Sibling Donor Hematopoietic Stem Cell Transplantation With Transcranial Doppler Velocities in Children With Sickle Cell Anemia.

Author information

1
Referral Center for Sickle Cell Disease, Department of Pediatrics, Intercommunal Créteil Hospital, University Paris-Est, Créteil, France.
2
Referral Center for Sickle Cell Disease, Medical Imaging Department, Intercommunal Créteil Hospital, Créteil, France.
3
Bone Marrow Transplant Unit, Department of Hematology, Saint-Louis Hospital, University Paris-Diderot, Paris, France.
4
Department of Pediatric Hematology, Robert-Debré Hospital, University Paris-Diderot, Paris, France.
5
Referral Center for Sickle Cell Disease, Department of Pediatrics, Necker Hospital, University Paris-Descartes, Paris, France.
6
Referral Center for Sickle Cell Disease, Pointe à Pitre, Guadeloupe, France.
7
Department of Pediatric Hematology, la Timone Hospital, Marseille University, Marseille, France.
8
Department of Pediatric Hematology, Hautepierre Hospital, Strasbourg University, Strasbourg, France.
9
Department of Pediatric Hematology, Necker Hospital, University Paris-Descartes, Paris, France.
10
Department of Pediatric Hematology, HIOP Lyon, Lyon, France.
11
Referral Center for Sickle Cell Disease, Department of Pediatrics, Kremlin-Bicêtre Hospital, University Paris-Sud, Paris, France.
12
Referral Center for Sickle Cell Disease, Department of Pediatrics, Robert-Debré Hospital, University Paris-Diderot, Paris, France.
13
Department of Pediatric Hematology, Bordeaux Hospital, Bordeaux, France.
14
Referral Center for Sickle Cell Disease, Department of Pediatrics, Fort de France, Martinique, France.
15
Department of Child and Adolescent Psychiatry, Avicenne Hospital, Paris-13 University, Paris, France.
16
Department of Medical Imagery, Debré Hospital, University Paris-Diderot, Paris, France.
17
Department of Statistics, Saint-Louis Hospital, ECSTRA Team, UMR1153, INSERM, University Paris-Diderot, Paris, France.

Abstract

Importance:

In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown.

Objective:

To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA.

Design, Setting, and Participants:

Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor.

Exposures:

MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching.

Main Outcomes and Measures:

The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years.

Results:

Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001).

Conclusions and Relevance:

Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up.

Trial Registration:

ClinicalTrials.gov Identifier: NCT01340404.

PMID:
30667500
PMCID:
PMC6439675
[Available on 2019-07-22]
DOI:
10.1001/jama.2018.20059
[Indexed for MEDLINE]

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