source: American Society of Hematology

year: 2017

authors: Valentine Brousse, Sara El Hoss, Naim Bouazza, Cecile Arnaud, Francoise Bernaudin, Beatrice Pellegrino, Corinne Guitton, Marie-Helene Odievre-Montanié, David Mames, Chantal Brouzes, Veronique Picard, Thao Nguyen-Khoa, Frederique Moatti, Catia Pereira, Claudine Lapoumeroulie, Serge Pissard, Caroline Le Van Kim, Yves Colin Aronovicz, Pierre Buffet, Mohandas Narla, Caroline Elie, Wassim El Nemer, Mariane De Montalembert

summary/abstract:

Infancy is a critical time during which the first complications of sickle cell anemia (SCA) emerge. Very early prognostic factors of severity are needed to select high-risk children to offer precisely tailored therapy. Our hypothesis was that clinical, biological or genetic parameters measurable soon after birth (3 to 6 months of age) could predict severe outcomes in the first two years of life in SCA infants.

Methods: Infants with SCA were offered to participate in a prospective study (ClinicalTrials.gov: NCT01207037) that included clinical and laboratory assessment at enrollment (3-6 months) and at 12, 18 and 24 months of age. The prognostic performance of conventional and SCA-specific biomarkers (notably erythroid adhesion markers, dense cells, ektacytometry indices) on disease severity was assessed using Cox’s proportional hazard regression models. The disease severity was defined as time to first occurrence of either acute splenic sequestration (ASS), vaso occlusive (VOC) event requiring hospitalization, transfusion, conditional or abnormal Trans Cranial Doppler, acute chest syndrome and death. Hazard ratios (HRs) were calculated with 95% Cis.

Results: Fifty-seven infants (55 SS; 2 Sβ°; 54.4% males), diagnosed through neonatal screening, were included in the study at a mean age of 4.4 ± 1 months and longitudinally assessed with a median follow-up of 19.4 months (range 3.1-23.2). Only 1 of 57 infants had experienced a SCA-related event prior to enrolment (dactilytis). At inclusion, clinical examinations were unremarkable except for pallor found in 15 (26,3%) and none of the infants had an enlarged or palpable spleen. Growth parameters were normal. Main biological characteristics were a mild hemolytic anemia (Hb 9.3 ±1.3 g/dL; reticulocytes count: 151.2 ±76 x 109/L), increased HbF level (3.8 ±1.3 g/dL. or 41.4 ±11.7%) and presence of dense red cells (23.1 % ±10.8). Genetic analysis showed one alpha globin deletion in 18 (32.1%) and a balanced distribution of beta globin haplotypes: 16 (30.8%), 18 (34.6%) and 18 (34.6%) in the favorable (SEN/SEN, BEN/SEN, CAM/SEN or SEN/ATYP), unfavorable (CAR/CAR, CAM/CAR, CAR/ATYP or BEN/CAR) and intermediate category (other) respectively. During the 2 years duration of the study, 44 of 57 (77%) infants required 157 hospital admissions, median (range): 2 (1-12) per patient. Infection was a leading cause of hospitalization although no serious adverse event related to pneumococcal infection was noted. Eight (14%) children experienced an episode of ASS at a median (range) age of 13.4 months (7.8- 15.9) while 13 infants (22.8%) experienced at least one VOC event at a median age of 12.7 months (7-22.5), with 6 experiencing ≥ 2 episodes. Nineteen infants (33.3%) required at least one transfusion with 10 (17.6%) requiring more than 2. Altogether, 22 (38.6%) infants of this cohort experienced a SCA-related severe clinical event by 24 months of age. The Kaplan Meier estimate of the 24-month event-free rate was 54.4% (95% CI, 39.7 to 74.5%).

organization: Hopital Universitaire Necker-Enfants Malades, Paris, France; Institut National de la Transfusion Sanguine (INTS), Paris, France; Université Sorbonne Paris Cité/Université Paris, France; Assistance Publique-Hopitaux de Paris, Paris, France; Université Paris Descartes, EA7323, Sorbonne Paris Cité, Paris, France; Referral Center for Sickle Cell Disease, CHIC, Créteil, France; Centre Hospitalier Poissy-Saint Germain, Poissy, France; Kremlin Bicetre Hospital, Kremlin Bicetre, France; Hôpital Universitaire Armand Trousseau, Paris, France; Hôpital UNiversitaire Tenon, Paris, France; Hôpital Universitaire Henri Mondor, Créteil, France; Laboratoire d'Excellence GR-Ex, Paris, France; Red Cell Physiology Laboratory, New York Blood Center, New York, NY

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