Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

Valentine Brousse; Sara El Hoss; Naïm Bouazza; Cécile Arnaud; Francoise Bernaudin; Béatrice Pellegrino; Corinne Guitton; Marie Hélène Odièvre-Montanié; David Mames; Chantal Brouzes; Véronique Picard; Thao Nguyen-Khoa; Catia Pereira; Claudine Lapouméroulie; Serge Pissard; Kate Gardner; Stephan Menzel; Caroline Le Van Kim; Yves Colin-Aronovicz; Pierre Buffet; Narla Mohandas; Caroline Elie; Micheline Maier-Redelsperger; Wassim El Nemer; Mariane de Montalembert

doi:10.1002/ajh.25260

Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

Valentine Brousse^*, Sara El Hoss, Naïm Bouazza, Cécile Arnaud, Francoise Bernaudin, Béatrice Pellegrino, Corinne Guitton, Marie Hélène Odièvre-Montanié, David Mames, Chantal Brouzes, Véronique Picard, Thao Nguyen-Khoa, Catia Pereira, Claudine Lapouméroulie, Serge Pissard, Kate Gardner, Stephan Menzel, Caroline Le Van Kim, Yves Colin-Aronovicz, Pierre BuffetNarla Mohandas, Caroline Elie, Micheline Maier-Redelsperger, Wassim El Nemer, Mariane de Montalembert

^*Corresponding author for this work

Institute of Psychiatry, Psychology & Neuroscience

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event—acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death—was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.

Original language	English
Pages (from-to)	1411-1419
Number of pages	9
Journal	American Journal of Hematology
Volume	93
Issue number	11
DOIs	https://doi.org/10.1002/ajh.25260
Publication status	Published - 1 Nov 2018

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Brousse, V., El Hoss, S., Bouazza, N., Arnaud, C., Bernaudin, F., Pellegrino, B., Guitton, C., Odièvre-Montanié, M. H., Mames, D., Brouzes, C., Picard, V., Nguyen-Khoa, T., Pereira, C., Lapouméroulie, C., Pissard, S., Gardner, K., Menzel, S., Le Van Kim, C., Colin-Aronovicz, Y., ... de Montalembert, M. (2018). Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study. American Journal of Hematology, 93(11), 1411-1419. https://doi.org/10.1002/ajh.25260

@article{5588792c95f34ff7aa287fcacba20bb1,

title = "Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study",

abstract = "In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event—acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death—was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.",

author = "Valentine Brousse and {El Hoss}, Sara and Na{\"i}m Bouazza and C{\'e}cile Arnaud and Francoise Bernaudin and B{\'e}atrice Pellegrino and Corinne Guitton and Odi{\`e}vre-Montani{\'e}, {Marie H{\'e}l{\`e}ne} and David Mames and Chantal Brouzes and V{\'e}ronique Picard and Thao Nguyen-Khoa and Catia Pereira and Claudine Lapoum{\'e}roulie and Serge Pissard and Kate Gardner and Stephan Menzel and {Le Van Kim}, Caroline and Yves Colin-Aronovicz and Pierre Buffet and Narla Mohandas and Caroline Elie and Micheline Maier-Redelsperger and {El Nemer}, Wassim and {de Montalembert}, Mariane",

year = "2018",

month = nov,

day = "1",

doi = "10.1002/ajh.25260",

language = "English",

volume = "93",

pages = "1411--1419",

journal = "American Journal of Hematology",

issn = "0361-8609",

publisher = "Wiley-Liss Inc.",

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Brousse, V, El Hoss, S, Bouazza, N, Arnaud, C, Bernaudin, F, Pellegrino, B, Guitton, C, Odièvre-Montanié, MH, Mames, D, Brouzes, C, Picard, V, Nguyen-Khoa, T, Pereira, C, Lapouméroulie, C, Pissard, S, Gardner, K , Menzel, S, Le Van Kim, C, Colin-Aronovicz, Y, Buffet, P, Mohandas, N, Elie, C, Maier-Redelsperger, M, El Nemer, W & de Montalembert, M 2018, 'Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study', American Journal of Hematology, vol. 93, no. 11, pp. 1411-1419. https://doi.org/10.1002/ajh.25260

TY - JOUR

T1 - Prognostic factors of disease severity in infants with sickle cell anemia

T2 - A comprehensive longitudinal cohort study

AU - Brousse, Valentine

AU - El Hoss, Sara

AU - Bouazza, Naïm

AU - Arnaud, Cécile

AU - Bernaudin, Francoise

AU - Pellegrino, Béatrice

AU - Guitton, Corinne

AU - Odièvre-Montanié, Marie Hélène

AU - Mames, David

AU - Brouzes, Chantal

AU - Picard, Véronique

AU - Nguyen-Khoa, Thao

AU - Pereira, Catia

AU - Lapouméroulie, Claudine

AU - Pissard, Serge

AU - Gardner, Kate

AU - Menzel, Stephan

AU - Le Van Kim, Caroline

AU - Colin-Aronovicz, Yves

AU - Buffet, Pierre

AU - Mohandas, Narla

AU - Elie, Caroline

AU - Maier-Redelsperger, Micheline

AU - El Nemer, Wassim

AU - de Montalembert, Mariane

PY - 2018/11/1

Y1 - 2018/11/1

N2 - In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event—acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death—was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.

AB - In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event—acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death—was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.

UR - http://www.scopus.com/inward/record.url?scp=85053676932&partnerID=8YFLogxK

U2 - 10.1002/ajh.25260

DO - 10.1002/ajh.25260

M3 - Article

C2 - 30132969

AN - SCOPUS:85053676932

SN - 0361-8609

VL - 93

SP - 1411

EP - 1419

JO - American Journal of Hematology

JF - American Journal of Hematology

IS - 11

ER -

Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

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