Abstract
Background: The FIP1L1-PDGFRA fusion, an imatinib-sensitive molecular target, is detected in a subset of cases with moderate-to-severe eosinophilia (eosinophil count ≥1500/μL). Using 2 FISH strategies to detect loss of the CHIC2 locus as a surrogate marker of the FIP1L1-PDGFRA fusion, we previously found 14% of cases to be CHIC2-deleted when studying bone marrow smears from 81 adult patients with moderate-to-severe, non-reactive eosinophilia at our institution (Blood 2004, 104:3038–3045). Since then, the FISH test has been made available for routine clinical use both within our institution, and to external physicians as a mail-in test, for the workup of patients with eosinophilic disorders, including systemic mast cell disease (SMCD).
Study design: FISH data, subsequent to the test’s introduction into routine clinical practice (from Nov. 2003), were retrospectively analyzed for CHIC2-deletion. Data from the initial pilot study of 81 patients was not used in this analysis (Table). The imatinib treatment analysis, however, included all CHIC2-deleted patients treated at our institution, including those from the pilot study (Table).
Results:
A total of 741 patients were studied in the post-pilot phase. Of these, 20 cases were found to be CHIC2-deleted, with an overall prevalence of 2.7% (Table).
Of the 219 patients seen at our institution, 13 (all male) were found to be CHIC2-deleted (Table) (prevalence=5.9%), and of these, 10 have been treated with imatinib (100 mg/day starting dose) to date. Nine patients are evaluable for response - all achieved a complete clinical and histological remission (7 patients were tested by FISH post-treatment - all achieved cytogenetic remission). One patient received concomitant corticosteroids for co-morbidities and could not be evaluated for response. After a median follow-up of 24 months (range 17 to 39 months), all 9 patients continue to be in remission, with a normal eosinophil count. At last follow-up, one patient had discontinued imatinib and the others were on maintenance therapy at the following dose: 100mg/wk (n=1), 100mg BIW (n=1), 100mg TIW (n=2), 50mg QOD (n=1), and 100 mg/day (n=3).
Conclusions:
FIP1L1-PDGFRA prevalence in non-selected patients with eosinophilia is lower than anticipated from prior studies.
Patients with FIP1L1-PDGFRA exhibit durable responses to imatinib therapy. It may be feasible to maintain some patients in remission on an empirically derived, intermittent schedule of low-dose imatinib.
. | Pilot Data . | Post-pilot Data (n=741) . | Total . | |
---|---|---|---|---|
. | Mayo samples . | Mayo samples . | Mail-in samples . | . |
Number of Patients | 81 | 138 | 603 | 822 |
Number CHIC2-deleted | 11 | 2 | 18 | 31 |
Prevalence | 14% | 1.4% | 3.0% | 3.8% |
Number Imatinib treated | 8 | 2 | n/a | 10 |
. | Pilot Data . | Post-pilot Data (n=741) . | Total . | |
---|---|---|---|---|
. | Mayo samples . | Mayo samples . | Mail-in samples . | . |
Number of Patients | 81 | 138 | 603 | 822 |
Number CHIC2-deleted | 11 | 2 | 18 | 31 |
Prevalence | 14% | 1.4% | 3.0% | 3.8% |
Number Imatinib treated | 8 | 2 | n/a | 10 |
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