Hematopoietic stem cell Transplantation in Children with very Early Onset Inflammatory Bowel Disease Secondary to Monogenic Disorders of immune-dysregulation

Satishkumar Meena; Harika Varla; Venkateswaran Vellaichamy Swaminathan; Rumesh Chandar; Indira Jayakumar; Balasubramaniam Ramakrishnan; Ramya Uppuluri; Revathi Raj

doi:10.1007/s12288-022-01586-2

Hematopoietic stem cell Transplantation in Children with very Early Onset Inflammatory Bowel Disease Secondary to Monogenic Disorders of immune-dysregulation

Indian J Hematol Blood Transfus. 2023 Apr;39(2):183-190. doi: 10.1007/s12288-022-01586-2. Epub 2022 Oct 26.

Authors

Satishkumar Meena¹, Harika Varla¹, Venkateswaran Vellaichamy Swaminathan¹, Rumesh Chandar¹, Indira Jayakumar², Balasubramaniam Ramakrishnan³, Ramya Uppuluri¹, Revathi Raj¹

Affiliations

¹ Department of PediatricHematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, 320, Padma complex, Anna Salai, 600035 Teynampet, Chennai, Tamil Nadu India.
² Department of Pediatric Critical Care Hospitals, Apollo Hospitals, 320, Padma complex, Anna Salai, 600035 Teynampet, Chennai, Tamil Nadu India.
³ Department of Biostatistics, Apollo Hospitals, 320, Padma complex, Anna Salai, 600035 Teynampet, Chennai, Tamil Nadu India.

Abstract

Background: Very early-onset inflammatory bowel disease (VEOIBD) is defined as IBD in children under six years of age. We present outcome data of hematopoietic stem cell transplantation (HSCT) in the above children. Patients and methods: We performed a retrospective study in children under six years of age who underwent HSCT for VEOIBD with an identified monogenic disorder from December 2012 to December 2020. Results: Of the 25 children included, the underlying diagnosis was IL10R deficiency (n = 4), Wiskott-Aldrich syndrome (n = 4), Leukocyte adhesion defect (n = 4), Hyper IgM syndrome (n = 3), Chronic granulomatous disease (n = 2), and one each with XIAP deficiency, severe congenital neutropenia, Omenn syndrome, Hyper IgE syndrome, Griscelli syndrome, MHC Class II deficiency, LRBA deficiency, and IPEX syndrome. Donors included a matched family donor in 10(40%); a matched unrelated donor in 8 (32%), haploidentical in 7 (28%) (T depleted 16%, T replete with post-transplant cyclophosphamide12%). Conditioning was myeloablative in 84% ofHSCTs. We documented engraftment in 22 (88%) children, primary graft failure in 2 children (8%), mixed chimerism in 6 (24%) children with mortality in 4/6 children. Children with a sustained chimerism of > 95% did not have recurrence of any features of IBD. Overall survival was 64%, with a median follow-up of 55 months. Mixed chimerism was associated with a significantly increased risk of mortality (p-value = 0.001). Conclusions: VEOIBD caused by monogenic disorders can be offered HSCT. Early recognition, optimal supportive care, and complete chimerism are essential components to achieving survival.

Keywords: HSCT; Haploidentical; IL10R deficiency; IPEX syndrome; LRBA deficiency; VEOIBD.

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