Pediatric myelodysplastic syndrome with inflammatory manifestations: Diagnosis, genetics, treatment, and outcome

Abstract

Background Inflammatory manifestations (IM) are well described in adult patients with myelodysplastic syndrome (MDS), but the presentation is highly variable and no standardized treatment exists. This phenomenon is rarely reported in children. As more pediatric patients are hematopoietic stem cell transplantation (HSCT) candidates, the role of anti‐inflammatory treatment in relation to HSCT should be defined. Procedure Here, we report a series of five children from a tertiary center. We describe the clinical presentation, molecular findings, and treatment options. Results All patients presented with advanced MDS with blast percentages ranging 10–30%, all had severe IM. One patient had MDS secondary to severe congenital neutropenia, the other four patients had presumably primary MDS. All four were found to harbor a PTPN11 gene driver mutation, which is found in 35% of cases of juvenile myelomonocytic leukemia (JMML). The mutation was present in the myeloid lineage but not in T lymphocytes. Three had symptoms of Behcet's‐like disease with trisomy 8 in their bone marrow. All patients were treated with anti‐inflammatory medications (mainly systemic steroids) in an attempt to bring them to allogeneic HSCT in a better clinical condition. All demonstrated clinical improvement as well as regression in their MDS status post anti‐inflammatory treatment. All have recovered from both MDS and their inflammatory symptoms post HSCT. Conclusion Primary pediatric MDS with IM is driven in some cases by PTPN11 mutations, and might be on the clinical spectrum of JMML. Anti‐inflammatory treatment may reverse MDS progression and improve the outcome of subsequent HSCT.

Allogeneic hematopoietic stem cell transplantation for juvenile myelomonocytic leukemia with intestinal Behçet's disease: A case report

“…At the same time, anti‐inflammatory treatment might serve as a bridge to allow JMML patients with BD undergo allo‐HSCT in better clinical condition. Systemic corticosteroids are considered the basis of treatment; however, a significant proportion of patients may require dual‐ or even third‐line therapy, such as immunomodulating agents and monoclonal antibodies 18 . Moreover, it has been reported that repeated cycles of hypomethylating agents can impact BD, resulting in a significant reduction in steroid dosage and dependency among a substantial number of patients 4,19 .…”

“…Systemic corticosteroids are considered the basis of treatment; however, a significant proportion of patients may require dual-or even third-line therapy, such as immunomodulating agents and monoclonal antibodies. 18 Moreover, it has been reported that repeated cycles of hypomethylating agents can impact BD, resulting in a significant reduction in steroid dosage and dependency among a substantial number of patients. 4,19 Furthermore, pre-transplantation azacitidine therapy has been reported as a suitable strategy to facilitate allo-HSCT and the outcomes are deemed satisfactory.…”

Chromosomal abnormalities related to fever of unknown origin in a Chinese pediatric cohort and literature review

“…Both patients with constitutional trisomy 8 [ 22 , 38 , 39 ] and patients with trisomy 8 in their bone marrow [ 19 – 21 , 23 , 40 , 41 ] have been reported to exhibit Behcet’s disease (BD) or other inflammatory disorders. CRP and interleukin (IL)-6 levels were significantly increased in patients with trisomy 8 during acute inflammation [ 20 , 42 ]. Inflammatory manifestations related to trisomy 8 in children are rarely reported.…”

“…Two patients in our study diagnosed with trisomy 8 had symptoms similar to BD, along with increased CRP/ESR levels and elevated IL-6 levels. Treatment with anti-inflammatory medications, such as systemic steroids, can improve clinical symptoms [ 20 , 39 ]. Trisomy 8 is also thought to increase the risk of the development of malignancy, especially myelodysplastic syndrome (MDS) symptoms [ 40 , 43 ].…”

“…In addition, P5 also carried the gene mutation c.1508G > C in PTPN11 . PTPN11 encodes the protein tyrosine phosphatase SHP2, a signal protein involved in the RAS/MAPK pathway [ 20 ]. The mutation c.1508G > C, either germline or somatic, has been reported to be associated with juvenile myelomonocytic leukemia [ 44 , 45 ], which requires hematopoietic stem cell transplantation.…”