Anti- Inflammatory Treatment in Pediatric Advanced Myelodysplastic Syndrome Associated with Inflammatory Manifestations May Reverse Progression and Bridge to a Successful HSCT

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Introduction Inflammatory Manifestations (IM) are well described in 10-30% of adult patients with Myelodysplastic Syndrome (MDS). Most case series do not report correlation between cytogenetic or MDS type. Different treatment modalities have been tried, but their role in relation to HSCT has not been established. Data for the pediatric MDS is scant. Methods We report here 4 pediatric cases of advanced MDS associated with IM who were diagnosed over a one year period in a tertiary pediatric center. Apart from routine MDS diagnostic methods, we tested patients for genetic predisposition, somatic mutations and cytokine levels to better characterize this entity. Results One patient was diagnosed with severe congenital neutropenia prior to MDS diagnosis, while the other 3 had primary MDS with no genetic background. Two of them were tested for somatic mutations and both harbored a somatic mutation in the PTPN11 gene. IM included Fever (N=4), Significant weight loss (N=3), Upper GI Ulcers (N=2), colitis (N=1), arthritis (N=1) and pulmonary congestion (N=2). All patients had Lansky score Systemic steroid treatment was initiated for all patients with at least partial clinical response observed in all. One patient was treated additionally with Anti IL 6 (Tocilizumab) monoclonal antibody (his serum IL6 was >log of the normal limit) and ATG. Bone marrow aspiration post treatment showed significant reduction in blast count in 3 patients, and complete normal hematopoiesis with no evidence of MDS in one patient. This patient remained in remission for 3 month and then his MDS relapsed with IM. Three patients had a matched sibling donor, and one patient had a 9/10 HLA matched unrelated donor. Myeloablative conditioning (Busulfan- Cyclophosphamide and Melphalan) was given to 3 patients, while one patient received reduced toxicity conditioning due to liver injury from ATG. All patients had neutrophil engraftment and 100% donor chimerisim. At a median follow up of 7 months, 3 patients are alive with no evidence of disease, and one patient died from HSCT complications. Conclusion MDS with IM is a significant entity in the pediatric population, demonstrating a heterogeneous phenotype and genetic background. Anti-inflammatory treatment may improve clinical symptoms and decrease blast count, bridging to a successful HSCT. Larger prospective studies with longer follow up are needed in order to better characterize this entity and its optimal treatment.

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