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