Abstract:
Background: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on AML patients with EMI.
Methods: We retrieved the clinical data of 713 pediatric AML patients from the TARGET dataset and analyzed the clinical and prognostic characteristics of patients with EMI at initial diagnosis and relapse.
Results: A total of 123 patients were identified to have EMI at initial diagnosis and 64 presented with EMI at relapse. We discovered that the presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in EMI relapse patients. Additionally, patients with EMI at diagnosis showed a reduced incidence of FLT3 ITD-/NPM1+, whereas EMI relapse patients displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower rate of CR1 and higher incidence of relapse. Importantly, EMI at diagnosis independently predicted both shorter EFS and OS. Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma exhibited a poorer OS compared to those with exclusive CNS involvement. Furthermore, in reference to patients with EMI at initial diagnosis, SCT failed to improve the survival, whereas GO treatment may potentially enhance OS.
Conclusion: EMI at initial diagnosis is an independent prognostic risk factor, GO treatment has the potential to improve survival for patients with EMI at diagnosis.
Introduction
Pediatric acute myeloid leukemia (AML) is a complicated and relatively rare hematological malignancy, constituting 15-20% of the total number pediatric acute leukemia patients. The prognosis of pediatric acute myeloid leukemia has seen notable improvements over the past few decades, with long-term survival rates of up to 70%. However approximately 30% of pediatric AML patients may experience relapse1. There are significant disparities in terms of clinical progression, outcomes, and genetic features between pediatric and adult AML patients1,2.
Extramedullary infiltration (EMI), also known as extramedullary disease (EMD), in AML presents as the infiltration of malignant clonal blasts in diverse anatomical sites apart from the bone marrow. These include other normal hematopoiesis from embryonic development onward (such as spleen, liver, thymus, and lymph nodes), soft tissue, skin, central nervous system (CNS), and other various organs or tissues3,4. The occurrence of EMI in pediatric AML patients ranges from 5.7% to 40% (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 AML patients post-transplantation experience isolated extramedullary relapse7.
In pediatric AML patients, the presence of EMI at diagnosis has been reported to be associated with young age, high WBC count, and FAB-M4/M5 subtypes8-12. Moreover, chromosomal abnormalities such as 11q23 abnormalities10-12, and t(8;21)12,13, have also been described in several studies. The outcome of EMI in pediatric AML patients is still controversial4. Some studies indicate that the presence of EMI at diagnosis was associated with a poorer prognosis11,14,15, while others indicate no significant influence on overall prognosis9,10. In certain subgroups, there were even suggestions of a potential association with improved outcomes12,16. However, there is a paucity of research on EMI at relapse in pediatric AML patients and little is known about the effect of SCT and GO treatment on the survival of AML patients presented with EMI.
The present study is a retrospective review of pediatric AML patients enrolled in COG trials AAML0531 and AAML03P1 from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset. We analyzed the clinical and prognostic characteristics of those who were identified with EMI (including myeloid sarcoma and/or CNS involvement in this study) at different time points (initial diagnosis and relapse) to gain a better understanding of this specific AML entity.
Methods