Background: Acute leukemia may be classified as myeloid, B, or T lymphoid in origin according to the antigenic profile of the blasts. Mixed-phenotype acute leukemia (MPAL) represents a rare heterogeneous group of acute leukemia in pediatric patients. MPAL has different clinicopathological and genetic character representatives, so diagnosis and treatment represent challenges. Management is more complex in low– middle-income countries (LMICs).
Aim: The primary aim of this study is to describe the diagnosis and
treatment outcomes of MPAL patients in a developing country.
Methods: In the present study, eight pediatric patients newly
diagnosed with MPAL from January 2005 until December 2015 were analyzed
retrospectively. Cytogenetic analysis showed chromosome complements in all the
metaphases from BM samples that follow the International System for Human
Cytogenetic Nomenclature. Patients were treated with AML- or ALL-like induction
therapy according to the BM aspirate immunophenotypic markers.
Results: Three pediatric patients (37.5%) were diagnosed with
T/Myeloid and Five (62.5%) with B/Myeloid through immunophenotyping of Eight
MPAL patients. There were seven males as well as one female. The average age
was 9 (range 4-13 years). Fever as well as lymphadenopathy were found in 6
(75%) as well as 4 (50%) of MPAL patients, respectively. We found KMT2A gene
rearrangement in one patient, Philadelphia-positive chromosomes in one, and
FMS-like tyrosine kinase three internal and duplication (FLT3-ITD) in two
patients. Eight patients (100%) received acute lymphoblastic leukemia (ALL)
induction; among them, six patients (75%) achieved complete remission (CR) with
no induction deaths as well as two of the eight patients with induction failure
were switched to AML therapy. Two patients (25%) started therapy with acute
myeloid leukemia (AML) induction as well as both (100%) achieved CR and then
received consolidation therapy after AML induction treatment. The 5-year
event-free survival (EFS) and overall survival (OS) rates were 75% and 100%,
while the cumulative incidence of relapse was found in one FLT3-ITD. B/myeloid,
as well as one KMT2A, rearranged gene T/myeloid (25%) with a median follow-up
duration of 8 years as well as treated with a hyper-CVAD regimen (combination of
chemotherapy drugs including cyclophosphamide, vincristine), Adriamycin, as
well as dexamethasone) induction, as well as achieved remission. Patients
treated with ALL-directed therapy had a 5-year EFS rate of 67% and an OS rate
of 100%. FLT3-ITD mutation showed a significantly lower 5-year EFS rate of 50%.
5-year EFS and the OS of MPAL patients were 60% and 100%, respectively. ALL
induction treatments demonstrated higher remission rates in pediatric MPAL
without mortality. Several studies have also investigated optimal upfront
therapy for patients with MPAL, as well as support the notion that ALL
treatment regimens tend to lead to better overall survival than AML-based
regimens.
Conclusion: ALL-directed therapy for pediatric MPAL is very
effective. However, more recently, the treatment has changed due to improved
diagnostic criteria, genomic techniques, and the observation that ALL-like
regimens in pediatric and adult populations are associated with superior
treatment response.
Author
(s) Details
Shah Kajal
Department of Medical Oncology and Pediatric Oncology, Gujarat Cancer
Research Institute, India.
Panchal Harsha
Department of Medical Oncology and Pediatric Oncology, Gujarat Cancer
Research Institute, India.
Patel Apurva
Department of Medical Oncology and Pediatric Oncology, Gujarat Cancer
Research Institute, India.
Chinmay Doctor
Department of Medical Oncology and Pediatric Oncology, Gujarat Cancer
Research Institute, India.
Yadav Rajan
Department of Medical Oncology and Pediatric Oncology, Gujarat Cancer
Research Institute, India.
Please see the book here:- https://doi.org/10.9734/bpi/acmms/v10/3183
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