Spontaneous Remission In An Older Patient With Relapsed Flt3 Itd Mutant Acute Myeloid Leukemia
Vachhani, P., Mendler, J. H., Evans, A., Deeb, G., Starostik, P., Wallace, P. K., & Wang, E. S. (2016). spontaneous Remission in an Older Patient with Relapsed FLT3 ITD Mutant acute myeloid leukemia. Case reports in hematology, 2016, 1259759. https://doi.org/10.1155/2016/1259759
View Original Source →Abstract
Spontaneous remission (SR) of acute myeloid leukemia (AML) is a very rare phenomenon. AML characterized by FLT3 internal tandem duplication (FLT3 ITD) is typically associated with an aggressive clinical course with rapid progression, relapse, and short overall survival in the absence of transplantation. We report here the first case of SR of FLT3 ITD mutant AML in the literature. Our patient was an elderly woman with relapsed NPM1 and FLT3 ITD mutant AML whose disease underwent SR for a brief duration without precipitating cause. We review the potential immune mechanisms underlying SR in AML and discuss the implications for novel immunotherapeutic approaches for FLT3 mutant AML.
Case Details
Disease Location
Blood/bone marrow
Personal Characteristics
73-year-old woman with a prior medical history of hypertension
Clinical Characteristics
Presented with three weeks of dyspnea, nausea, loose stools, and fatigue. Complete blood count revealed leukocytes of 240,000/𝜇l, hemoglobin of 6.2 g/dl, and platelets of 119,000/𝜇l peripheral smear showed many pro monocytes and a few immature blasts containing rare auer rods consistent with a diagnosis of acute myeloid leukemia flt-3 itd and exon 12 mutation of the nucleophosmin-1 (npm1) gene were detected consistent with npm1-mutated acute myeloid leukemia of fab m5 subtype. The patient achieved a complete remission based on count recovery and repeat bone marrow aspirate showing no blasts or pro monocytes. No flt3 mutation was identified by quantitative pcr in the marrow; however, exon 12 mutation of npm1 was identified in a very small fraction of the cells six months after completion of consolidation therapy and eight months from her diagnosis, the patient was noted on routine follow-up to have mild leukopenia and and thrombocytopenia. Repeat bone marrow biopsy and aspirate (figure 1(a)) showed 64% myeloblasts. Cytogenetics revealed a new abnormality in the form of del (15q) in 19/20 analyzed cells. Both npm1 and flt3 itd mutations were identified with a flt3 itd allele/wild-type ratio of 0.36. The patient was referred to a clinical trial of an experimental flt3 inhibitor.
Remission Characteristics
She underwent screening bone marrow biopsy and aspirate (before initiating the clinical trail) on the contralateral side from bm-1 approximately one week apart. Surprisingly, this demonstrated cellular marrow with 3% blasts without auer rods and no evidence of acute myeloid leukemia by marrow ihc and fc. Given these incongruent marrow findings, another bone marrow biopsy and aspirate procedure (figure 1(c)) was performed on the ipsilateral side as bm-1 another week later. This specimen also showed no evidence of acute myeloid leukemia by morphology or fc with 2% blasts.
Treatment & Mechanisms
Proposed Remission Mechanisms
Innate host immune responses
Clinical Treatment
Leukopheresis and hydroxyurea induction chemotherapy (cytarabine and daunorubicin)