S112: COMPARATIVE SCORE OF HOWELL-JOLLY BODIES IN SICKLE CELL DISEASE PATIENTS ACCORDING TO GENOTYPE, AGE, SPLENECTOMY OR STEM CELL TRANSPLANTATION HISTORY

Abstract

Background: Presence of Howell-Jolly bodies is associated with splenic dysfunction which progressively appears during aging or after splenectomy in patients with sickle cell disease. Improvement of splenic function has been found in several transplanted patients for SCD (Ferster 1993, Bernaudin 2007) encouraging our team to propose partial splenectomy to patients with hypersplenism and available matched-sibling donor. Aims: The goal of the present study was to evaluate the outcome of the splenic function from birth to adult age and the impact of splenectomy (partial or total) in SCD patients transplanted or not. Patients and Methods: In the pediatric Créteil SCD-cohort, including 907 SCD patients (111 SC, 47 Sb+, 725 SS, 21 Sb0 and 3 SDPunjab), Howell-Jolly bodies score (from 0 to 4) was prospectively assessed and recorded at each annual check-up. This study included 5013 annual check-ups (637 in SC/Sb+ and 4376 in SS/Sb0 patients) from Jan 1991 to July 2019. Results: Howell-Jolly bodies mean score increased during aging in SCD patients but was significantly lower in SC/Sb+ than in SS/Sb0 patients at each age of assessment (Figure 1). During the 2nd year of life, mean (SD Howell-Jolly bodies score was 0.34 (0.61) in SC/Sb+ vs 0.69 (0.82) in SS/Sb0 (P=0.01) while during the 18th year it was 0.61 (0.61) in SC/Sb+ vs 1.33 (1.1) in SS/Sb0 children (P<0.001). Among 749 SCA children, 86 were splenectomized at mean (SD) age of 6.4 years (3.9). As expected, mean (SD) Howell-Jolly bodies score was significantly higher at check-up in splenectomized than in non-splenectomized SCA-patients: 1.73 (1.2) vs 1.1 (1.0), p<0.001. However, the difference between both populations decreased during aging because of the progressive functional splenic dysfunction in non-splenectomized patients (Figure 2) Among SCA-children, 138 were transplanted with matched sibling donor at mean (SD) age of 9.0 years (4.9y). At each age of assessment, Howell-Jolly bodies score was strongly significantly (p<0.001) lower in transplanted than in non-transplanted children (Figure 3). At check-up performed during the 18th year of life, mean (SD) Howell-Jolly bodies score was 1.57 (1.0) in 241 non transplanted vs 0.54 (0.9) in 70 transplanted children (p<0.001) and the score in transplanted children was significantly positively correlated with the age at transplant (r=0.335, p=0.002). Seven children with splenic sequestration history or hypersplenism and available MSD-donor had partial splenectomy before transplant in order to try to preserve splenic function. Mean (SD) Howell-Jolly bodies score was 1.83 (1.2) before and was nul after transplant in all seven children.Conclusion: This cohort study clearly shows that splenic dysfunction increases during aging in SCA children and that stem cell transplantation allows to preserve splenic function especially since the transplant is performed early. In children with indication of splenectomy for recurrent splenic sequestrations or hypersplenism who have an available matched sibling donor, the present study encourages to propose partial vs total splenectomy just before stem cell transplantation in order to preserve splenic function.