FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia: A Low-Burden Disease with Dramatic Response to Imatinib - A Report of 5 Cases from South India

Abstract

Objective: Eosinophilia associated with FIP1L1-PDGFRA rearrangement represents a subset of chronic eosinophilic leukemia and affected patients are sensitive to imatinib treatment. This study was undertaken to learn the prevalence and associated clinicopathologic and genetic features of FIP1L1-PDGFRA rearrangement in a cohort of 26 adult patients presenting with profound eosinophilia (>1.5x109/L).Materials and Methods: Reverse-transcriptase polymerase chain reaction and gel electrophoresis were used for the detection of FIP1L1-PDGFRA rearrangement. Results: Five male patients with splenomegaly carried the FIP1L1-PDGFRA gene rearrangement. All patients achieved complete hematological response within 4 weeks of starting imatinib. One patient had previous deep vein thrombosis and 1 patient had cardiomyopathy, which improved with steroids and imatinib. Conventional cytogenetics was normal in all these patients. No primary resistance to imatinib was noted.Conclusion: This study indicates the need to do the FIP1L1-PDGFRA assay in patients with hypereosinophilic syndrome. Prompt treatment of this condition with imatinib can lead to complete hematological response and resolution of the organ damage that can be seen in this setting.

Paratrabecular myelofibrosis and occult mastocytosis are strong morphological clues to suspect FIP1L1-PDGFRA translocation in hypereosinophilia

“…The frequency of F/P ? HE/HES ranges from 3-56% in the literature [1,[5][6][7][8][9][10]. The current study shows a prevalence of 13.3% in consecutive 45 patients who underwent FISH testing for F/P translocation over a period of 17 months.…”

“…The exact prevalence of HE associated with FIP1L1-PDGFRA rearrangement (F/P?ve HE) in tropical countries is not known. A previous case series from South India reported a frequency of 19.2% among 26 adults with HE [5]. The frequency of F/P ?…”

“…It involves the constitutive activation of tyrosine kinases due to FIP1L1-PDGFRA (F/P) translocation that are highly sensitive to tyrosine kinase inhibitor (TKI) Imatinib [2,3]. There are only a few reports of F/P?ve HES from tropical countries [1,4,5] which otherwise have a high burden of parasitic infection associated HE. In the absence of well-characterized morphological features, F/P?ve HE continues to be underdiagnosed in resource limited settings.…”

Identification of a novel PDGFRA point mutation at p.P6L as a potential molecular target of imatinib in an eosinophilia patient showing genetic heterogeneity

“…Imatinib was also found to be particularly effective towards eosinophilia secondary to myeloproliferative leukemia. 19 Accompanying the FIP1L1-PDGFRA fusion gene and PDGFRA gene point mutation in our patient, MYOM2 and ASXL3 gene point mutations were also identified by NGS, suggesting his cancer was heterogeneous. The MYOM2 gene plays a significant role in recurrent diffuse large B-cell lymphoma.…”

Severe Eosinophilia Associated with FIP1L1/PDGFRA Rearrangement Presenting with Yamaguchi Syndrome

“…Our patient is a case of chronic eosinophilic leukemia associated with PDGFRA rearrangement, presenting with severe eosinophilia and evidence of multi-organ damage. Several case reports and case series of patients with eosinophilia associated with FIP1L1/PDGFRA rearrangement, have been published from various countries [7][8][9][10][11][12][13][14][15][16][17][18]. In addition to the more common presentations, they have described the clinical features and outcome of this rare disease entity in paediatric patients, the occurrence of rare FIP1L1 breakpoint (located outside the usual breakpoint region) and atypical presentation of the disease with thrombotic thrombocytopenia purpura.…”