Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology

Abstract

Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.

Extramedullary infiltration in pediatric acute myeloid leukemia: Results from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative

“…were diagnosed with EMI at initial diagnosis, which is consistent with that previously reported. 4 However, certain patients with EMI may remain asymptomatic or lack BM involvement. The routine use of lumbar puncture, incorporation of flow cytometry as a part of cerebrospinal fluid assessment, and variations in the type and frequency of imaging examinations could impact the detection rate of EMI.…”

“…(commonly 10%-25%), 4 much higher than in adult patients, which is around 4.7%-14.21%. 5,6 Furthermore, approximately 3.5% of pediatric patients with AML experience isolated extramedullary relapse after transplantation.…”

“…The outcome of EMI in pediatric patients with AML is still controversial. 4 Some studies indicate that the presence of EMI at diagnosis is associated with a poorer prognosis, 11,14,15 while others indicate no significant influence on overall prognosis. 9,10 In certain subgroups, there are even suggestions of a potential association with improved outcomes.…”

Primary myeloid sarcoma in an infant with an NRAS mutation

“…There is no defined standard-of-care treatment, though most patients receive AML-directed chemotherapy (typically including an anthracycline, cytarabine, and etoposide), as well as some combination of surgery and radiation therapy for local control. 2 Prognosis of isolated MS is quite variable and is dependent on the site of involvement and molecular characteristics, with orbital and CNS involvement having the lowest rate of relapse and highest event-free survival. 2,5 A literature review for isolated pediatric MS revealed 14 total cases (review limited to literature available in English).…”

“…2 Prognosis of isolated MS is quite variable and is dependent on the site of involvement and molecular characteristics, with orbital and CNS involvement having the lowest rate of relapse and highest event-free survival. 2,5 A literature review for isolated pediatric MS revealed 14 total cases (review limited to literature available in English). All patients received AML-directed therapy with most achieving durable complete remission.…”