THE WHO SUBCATEGORY 'MYELOID/LYMPHOID NEOPLASMS WITH EOSINOPHILIA AND REARRANGEMENT OF PDGFRA, PDGFRB OR FGFR1, OR PCM1-JAK2' REVISITED IN 74 PATIENTS: LACK OF EOSINOPHILIA AND PRESENCE OF MONOCYTOSIS
Author(s): ,
Georgia Metzgeroth
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Laurenz Steiner
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Juliana Schwaab
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Nicole Naumann
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Mohamad Jawhar
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Sebastian Kreil
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Torsten Haferlach
Affiliations:
Munich Leukemia Laboratory,Munich,Germany
,
Alice Fabarius
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Wolf-Karsten Hofmann
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
,
Nicholas C. P. Cross
Affiliations:
Wessex Regional Genetics Laboratory,Salisbury,United Kingdom;Faculty of Medicine, University of Southampton,Southampton,United Kingdom
Andreas Reiter
Affiliations:
Department of Hematology and Oncology,University Hospital Mannheim, Heidelberg University,Mannheim,Germany
EHA Library. Steiner L. 06/12/20; 293591; EP1102
Mr. Laurenz Steiner
Mr. Laurenz Steiner
Contributions
Abstract

Abstract: EP1102

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
The World Health Organization (WHO) defines a distinct subcategory of myeloid neoplasms as 'myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2 '. However, lack of eosinophilia and presence of monocytosis has been reported in some cases. In contrast, fusion genes with involvement of alternative tyrosine kinases, e.g. ETV6-ABL1, have not been included

Aims
We sought to investigate the presence or absence of eosinophilia and monocytosis in patients with rearrangement of PDGFRA (FIP1L1-PDGFRA, n=44), PDGFRB (diverse, n=16) and FGFR1 (diverse, n=6) and JAK2 (diverse, n=8). In addition, we evaluated ETV6-ABL1 positive patients (n=6).

Methods
Retrospective analysis of registry data.

Results
In FIP1L1-PDGFRA positive patients, eosinophilia (median 6.4 x 109/l, range 0.9-30.1) >0.5 x 109/l or >1.5 x 109/l was observed in 44/44 (100%) and 40/44 (90%) patients, respectively. Monocytosis >1.0 x 109/l was present in 12/44 (27%) patients. There was a significant correlation between the absolute numbers of eosinophils and monocytes (r=0.49, p0.5 x 109 /l and >1.5 x 109 /l in 4/16 (25%), 12/16 (75%) and 8/16 (50%) patients, respectively. In patients with FGFR1 fusion genes (median 0.6 x 109 /l, range 0-2.5), respective numbers were 3/6 (50%), 3/6 (50%) and 1/6 (17%), respectively. In patients with JAK2 fusion genes, eosinophils (median 1.5 x 109 /l, range 0-4.6) were ≤0.5 x 109 /l, >0.5 x 109 /l and >1.5 x 109 /l in 2/8 (25%), 6/8 (75%) and 4/8 (50%) patients, respectively. Overall, significant monocytosis >1.0 x 109 /l was observed in 21/74 (28%) patients (PDGFRA, 12/44, 27%; PDGFRB, 5/16, 31%; FGFR1, 2/6, 33%; JAK2, 2/8, 25%). Monocytosis >1.0 x 109 /l was clearly associated with eosinophilia >1.5 x 109 /l (17/21, 81%). Blast phase was diagnosed in 7/21 (33%, FIP1L1-PDGFRA, n=6; FGFR1, n=1) of those patients. ETV6-ABL1 positive patients presented with eosinophilia (median 5.9 x 109 /l, range 2.0-7.1) >1.5 x 109 /l in 6/6 (100%) cases, with associated monocytosis >1.0 x 109 /l in 5/6 (83%) patients (Table 1).

Conclusion
a) in patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, eosinophilia is consistently only associated with FIP1L1-PDGFRA (although we acknowledge an obvious ascertainment bias in that only cases with eosinophilia are usually screened routinely for FIP1L1-PDGFRA), b) lack of eosinophilia is observed in more than 25% of patients with PDGFRB, FGFR1 or JAK2 fusion genes and c) monocytosis >1.0 x 109 /l is present in a significant proportion of patients and is associated with eosinophilia >1.5 x 109 /l and d) ETV6-ABL1 positive patients have a clear phenotypic overlap with FIP1L1-PDGFRA positive patients, in consequence, the ETV6-ABL1 fusion gene should be included in this subcategory. Due to these findings and also because lymphoblastic leukemia/lymphoma frequently represents medullary or extramedullary lymphoid blast phase of the underlying myeloid neoplasm/stem cell neoplasm in patients with tyrosine kinase fusions (Metzgeroth et al., Leukemia 2007 and Leukemia 2013), we suggest that this subcategory should be recategorised into either 'myeloid neoplasms with tyrosine kinase fusion genes' (with the major subcategory being BCR-ABL1 positive chronic myeloid leukemia) or 'myeloid neoplasms with tyrosine kinase fusion genes, other than BCR-ABL1'.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Abstract: EP1102

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
The World Health Organization (WHO) defines a distinct subcategory of myeloid neoplasms as 'myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2 '. However, lack of eosinophilia and presence of monocytosis has been reported in some cases. In contrast, fusion genes with involvement of alternative tyrosine kinases, e.g. ETV6-ABL1, have not been included

Aims
We sought to investigate the presence or absence of eosinophilia and monocytosis in patients with rearrangement of PDGFRA (FIP1L1-PDGFRA, n=44), PDGFRB (diverse, n=16) and FGFR1 (diverse, n=6) and JAK2 (diverse, n=8). In addition, we evaluated ETV6-ABL1 positive patients (n=6).

Methods
Retrospective analysis of registry data.

Results
In FIP1L1-PDGFRA positive patients, eosinophilia (median 6.4 x 109/l, range 0.9-30.1) >0.5 x 109/l or >1.5 x 109/l was observed in 44/44 (100%) and 40/44 (90%) patients, respectively. Monocytosis >1.0 x 109/l was present in 12/44 (27%) patients. There was a significant correlation between the absolute numbers of eosinophils and monocytes (r=0.49, p0.5 x 109 /l and >1.5 x 109 /l in 4/16 (25%), 12/16 (75%) and 8/16 (50%) patients, respectively. In patients with FGFR1 fusion genes (median 0.6 x 109 /l, range 0-2.5), respective numbers were 3/6 (50%), 3/6 (50%) and 1/6 (17%), respectively. In patients with JAK2 fusion genes, eosinophils (median 1.5 x 109 /l, range 0-4.6) were ≤0.5 x 109 /l, >0.5 x 109 /l and >1.5 x 109 /l in 2/8 (25%), 6/8 (75%) and 4/8 (50%) patients, respectively. Overall, significant monocytosis >1.0 x 109 /l was observed in 21/74 (28%) patients (PDGFRA, 12/44, 27%; PDGFRB, 5/16, 31%; FGFR1, 2/6, 33%; JAK2, 2/8, 25%). Monocytosis >1.0 x 109 /l was clearly associated with eosinophilia >1.5 x 109 /l (17/21, 81%). Blast phase was diagnosed in 7/21 (33%, FIP1L1-PDGFRA, n=6; FGFR1, n=1) of those patients. ETV6-ABL1 positive patients presented with eosinophilia (median 5.9 x 109 /l, range 2.0-7.1) >1.5 x 109 /l in 6/6 (100%) cases, with associated monocytosis >1.0 x 109 /l in 5/6 (83%) patients (Table 1).

Conclusion
a) in patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2, eosinophilia is consistently only associated with FIP1L1-PDGFRA (although we acknowledge an obvious ascertainment bias in that only cases with eosinophilia are usually screened routinely for FIP1L1-PDGFRA), b) lack of eosinophilia is observed in more than 25% of patients with PDGFRB, FGFR1 or JAK2 fusion genes and c) monocytosis >1.0 x 109 /l is present in a significant proportion of patients and is associated with eosinophilia >1.5 x 109 /l and d) ETV6-ABL1 positive patients have a clear phenotypic overlap with FIP1L1-PDGFRA positive patients, in consequence, the ETV6-ABL1 fusion gene should be included in this subcategory. Due to these findings and also because lymphoblastic leukemia/lymphoma frequently represents medullary or extramedullary lymphoid blast phase of the underlying myeloid neoplasm/stem cell neoplasm in patients with tyrosine kinase fusions (Metzgeroth et al., Leukemia 2007 and Leukemia 2013), we suggest that this subcategory should be recategorised into either 'myeloid neoplasms with tyrosine kinase fusion genes' (with the major subcategory being BCR-ABL1 positive chronic myeloid leukemia) or 'myeloid neoplasms with tyrosine kinase fusion genes, other than BCR-ABL1'.

Session topic: 16. Myeloproliferative neoplasms - Clinical

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies