Abstract
Background: Patients with stem cell myeloproliferative disorders have a particularly poor prognosis and limited treatment options, i.e. mainly aggressive chemotherapy or allogeneic stem cell transplantation. In 2004, Chen et al. reported a patient presenting a t(8;13) (p11;q12) cytogenic anomaly who responded positively to treatment with PKC412 (midostaurin), an oral multi-targeted tyrosine kinase inhibitor. Here, we report a second case treated with the above-mentioned drug. Patient: A 71-year-old woman was diagnosed as having chronic myelogenous leukaemia with eosinophilia secondary to t(8;13) with FGFR1 involvement. Due to her age, an allogeneic stem cell transplantation was not possible. Treatment: A treatment combining aggressive chemotherapy and midostaurin was explored. The patient received one cycle of hyper-CVAD chemotherapy followed by maintenance therapy with midostaurin. A relapse occurred after six months, and she was treated with four more cycles of hyper-CVAD chemotherapy. The patient entered a complete clinical, haematological and cytogenetic remission. A maintenance therapy with midostaurin continued for four months until she developed a chemoresistant relapse followed by acute leukaemia. Conclusion: This is the second case of a t(8;13) myeloid and lymphoid neoplasm with FGFR1 abnormalities treated successfully with midostaurin. Midostaurin is administered orally, allows for outpatient care and in this case showed only occasional and minimal side effects. The combination of hyper-CVAD and midostaurin extended survival by 21 months without allogeneic transplantation. This case further supports the possibility of using midostaurin for the treatment of other diseases with FGFR1 dysregulations; however, specific clinical trials are needed to confirm this hypothesis.
Highlights
WHO has proposed two categories for myeloid neoplasms presenting with eosinophilia: 1) Chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS), and 2) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or of the fibroblast growth factor receptor 1 (FGFR1) [1]
WHO classification states that all patients with abnormalities in PDGFRA, PDGFRB or FGFR1 genes need further diagnostic evaluation in order to differentiate between CEL, MPN, acute myeloid leukaemia (AML), T-lymphoblastic lymphoma or other malignancies [3] [4]
Karyotyping and FISH analysis established the presence of a t(8;13) translocation and a breakpoint within the fibroblast growth factor receptor 1 (FGFR1), the receptor tyrosine kinase that is known to be disrupted in myeloproliferative disorders, leading to the final diagnosis of myeloid and lymphoid neoplasia with eosinophilia and FGFR1 abnormality (Figure 1)
Summary
WHO has proposed two categories for myeloid neoplasms presenting with eosinophilia: 1) Chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS), and 2) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or of the fibroblast growth factor receptor 1 (FGFR1) [1]. WHO classification states that all patients with abnormalities in PDGFRA, PDGFRB or FGFR1 genes need further diagnostic evaluation in order to differentiate between CEL, MPN, acute myeloid leukaemia (AML), T-lymphoblastic lymphoma or other malignancies [3] [4]. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of FGFR1 derive from a pluripotent haematopoietic stem cell. We describe here the first patient who has survived chronic myeloid leukaemia with eosinophilia and FGFR1 mutation for over 22 months without stem cell transplantation. The sequential administration of hyper-CVAD chemotherapy and midostaurin as maintenance therapy translated in a significant tumour reduction and control of progression
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