Long-term follow-up of treatment with imatinib in eosinophilia-associated myeloid/lymphoid neoplasms with PDGFR rearrangements in blast phase

Abstract

treated with vitamin E, which reduced ROS by approximately twofold (Figure 1a). 9,11 Human CD45 þ cells collected from bone marrows and spleens of NSG mice formed colonies in vitro, and vitamin E treatment did not affect the engraftment (Figure 1b). Imatinib-resistant clones carrying either E255K or T315I BCR-ABL1 kinase mutations were detected in three out of five untreated xenografts, but in none of the vitamin E-treated samples (Table 1). In conclusion, we postulate that anti-oxidants such as vitamin E may be applicable in prevention of TKI-resistance, in particular of that driven by BCR-ABL1 kinase mutations. Moreover, as imatinibtreated CML-CP LSCs and LPCs continue to accumulate high levels of ROS resulting in TKI-resistant mutations, 9,10 anti-oxidant treatment could be combined with TKIs to extend/improve the therapeutic effects of ABL1 kinase inhibitors. This speculation is reinforced by the observation that anti-oxidants vitamin E and N-acetyl-cysteine reduced the percentage of the resistant clones emerging in vitro from imatinib-treated BCR-ABL1-positive cells. 11

Myeloid neoplasms with eosinophilia

“…27, [95][96][97] We are aware of several cases in which a fusion gene has only come to attention after patients achieved clearance of blasts or remission of lymphomas with intensive chemotherapy but significant eosinophilia persisted. If performed, molecular analyses have shown that the genetic lesion is usually detectable in granulocytic cells, but also in blasts of myeloid or lymphoid origin, indicating a stem cell disorder with multilineage involvement and a disparate morphologic appearance in BM and lymph nodes.…”

“…97 Two patients were initially treated with intensive chemotherapy instead of imatinib, but failed to achieve a complete remission; subsequent allogeneic HSCT was shortly followed by relapse within 3 months. 97 The combination of imatinib and intensive chemotherapy, similar to that which has been undertaken with ALL induction regimens such as hyperCVAD in BCR-ABL1-positive ALL, merits further investigation. More data are also needed regarding the role of allogeneic HSCT, given the few numbers of PDGFRA/Bpositive blast phase patients treated to date.…”

Sustained Response to Imatinib in a Pediatric Patient with Concurrent Myeloproliferative Disease and Lymphoblastic Lymphoma Associated with a <b><i>CCDC88C-PDGFRB</i></b> Fusion Gene

“…The effectiveness of imatinib treatment was also demonstrated in patients with myeloid/lymphoid PDGFR rearrangement in blast phase. Some of them failed prior treatment with intensive chemotherapy and stem cell transplantation and achieved complete hema­tologic response after initiation of imatinib [5]. The concurrent occurrence of lymphoblastic lymphoma with myeloproliferative disorder is not unusual in cases with abnormalities of FGFR1 and PDGFRA , but the association with PDGFRB -rearranged myeloid neoplasms was described only in the last years in few adult cases.…”

“…The vast majority of myeloproliferative disorders with this translocation were described in adults and were sensitive to treatment with the tyrosine kinase inhibitor imatinib. The association of PDGFRB -rearranged myeloid disorder with T-lymphoblastic lymphoma was first described by Chang et al [4] in an adult patient with concurrent acute myeloid leukemia and T-lymphoblastic lymphoma, followed later by several additional reports of adult patients [5-7]. The CCDC88C (formerly reported as KIAA1509 ) gene was first identified as a fusion partner in an adult patient with myeloproliferative disease but with no lymphatic involvement, associated with a t(5; 14)(q33;q32) translocation [8].…”

The FIP1L1-PDGFRA fusion gene and the KIT D816V mutation are coexisting in a small subset of myeloid/lymphoid neoplasms with eosinophilia

“…These disorders include thrombosis, small vessel vasculitis, systemic lupus erythematosus, autoimmunity, pneumonia, sepsis, and blood transfusion-related acute lung injury. [1][2][3][4] NETs are DNA-based extracellular traps that not only trap and kill invading microbes but also BLOOD, 23 JANUARY 2014 x VOLUME 123, NUMBER 4 CORRESPONDENCE 597…”