Successful non‐myeloablative allogeneic transplantation for treatment of idiopathic hypereosinophilic syndrome

Ueno, Naoto T.; Anagnostopoulos, Athanasios; Rondón, Gabriela; Champlin, Richard E.; Mikhailova, N.; Pankratova, O. S.; Zoubarovskaya, L. S.; Семенова, Е. В.; Afanasyev, Boris; O’Brien, Susan; Andreeff, Michael; Zaritskey, Andrey

doi:10.1046/j.1365-2141.2002.03771.x

Cited by 66 publications

(32 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High-dose chemotherapy has been proposed for the treatment of very aggressive forms. 1,4,5 The case reported here illustrates that even after failure of very intensive treatment, rapid and sustained molecular response can be achieved using imatinib therapy. Analysis of the FIP1L1-PDGFRA fusion transcript appears very helpful in HES, in order to identify patients with FIP1L1-PDGFRA fusion transcripts with a high probability of responding …”

mentioning

confidence: 92%

Sustained molecular response with imatinib in a leukemic form of idiopathic hypereosinophilic syndrome in relapse after allograft

et al. 2003

View full text Add to dashboard Cite

mentioning

confidence: 92%

Sustained molecular response with imatinib in a leukemic form of idiopathic hypereosinophilic syndrome in relapse after allograft

et al. 2003

View full text Add to dashboard Cite

“…157 Allogeneic transplantation using nonmyeloablative conditioning regimens has been reported in 3 patients, with remission duration of 3 to 12 months at the time of last reported follow-up. 158,159 Despite success in selected cases, the role of transplantation in HES is not well established. Transplantation-related complications including acute and chronic graft versus host disease as well as serious infections have been frequently observed.…”

Section: Current Treatmentmentioning

confidence: 99%

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

Gotlib

Cools

Malone

et al. 2004

Blood

262

205

View full text Add to dashboard Cite

Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and CEL are imatinib-responsive malignancies, with rapid and complete hematologic remissions observed at lower doses than used in chronic myelogenous leukemia (CML). These BCR-ABL-negative cases lack activating mutations or abnormal fusions involving other known target genes of imatinib, implicating a novel tyrosine kinase in their pathogenesis. A bedside-to-benchtop translational research effort led to the identification of a constitutively activated fusion tyrosine kinase on chromosome 4q12, derived from an interstitial deletion, that fuses the platelet-derived growth factor receptor-␣ gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FIP1L1). However, not all HES and CEL patients respond to imatinib, suggesting disease heterogeneity. Furthermore, approximately 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity. This review examines the current state of knowledge of HES and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and management. IntroductionProtean biologic and clinical presentations characterize idiopathic hypereosinophilia (HES). HES is similar to other diseases given the moniker "diagnosis of exclusion," in that limited understanding of the pathogenesis of the disease has hampered therapeutic advances. The demonstration of increased myeloblasts or clonality or the development of either granulocytic sarcoma or acute myeloid leukemia helps clarify the origin of some cases of chronic eosinophilic leukemia. 1 In a subset of patients, hypereosinophilia is related to excessive secretion of eosinophilopoietic cytokines from a clonal population of lymphocytes. 2 The identification of FIP1-like-1-platelet-derived growth factor receptor-␣ (FIP1L1-PDGFRA) in cases of HES/CEL adds to a growing list of activated fusion tyrosine kinases linked to the pathogenesis of chronic myeloproliferative disorders. 3 It is unique, however, because it is the first description of a gain-of-function fusion protein resulting from a cryptic interstitial deletion between genes rather than a reciprocal chromosomal translocation. The FIP1L1-PDGFR␣ fusion protein transforms hematopoietic cells, and its kinase activity is inhibited by imatinib at a cellular 50% inhibitory concentration (IC 50 ) 100-fold lower than BCR-ABL. 3 Acquisition of an imatinib resistance mutation in the adenosine triphosphate (ATP)-binding domain of PDGFRA in a relapsed patient previously responsive to imatinib supports a critical role for FIP1L1-PDGFR␣ in the pathogenesis of disease and demonstrates that FIP1L1-PDGFR␣ is the therapeutic target of imatinib. 3 The identification of t...

show abstract

“…62,63 Finally, few case reports have shown successful treatment of HES or clonal eosinophilia, including a FIP1L1-PDGFRA-positive case, with either conventional or reduced-intensity conditioning allogeneic hematopoietic cell transplant. [64][65][66] We think that such therapy should be considered for drug-refractory HES or clonal eosinophilia.…”

Section: Management Of Hesmentioning

confidence: 99%

Hypereosinophilic Syndrome and Clonal Eosinophilia: Point-of-Care Diagnostic Algorithm and Treatment Update

Tefferi

Gotlib²,

Pardanani

2010

Mayo Clinic Proceedings

139

136

View full text Add to dashboard Cite

Successful non‐myeloablative allogeneic transplantation for treatment of idiopathic hypereosinophilic syndrome

Cited by 66 publications

References 15 publications

Sustained molecular response with imatinib in a leukemic form of idiopathic hypereosinophilic syndrome in relapse after allograft

Sustained molecular response with imatinib in a leukemic form of idiopathic hypereosinophilic syndrome in relapse after allograft

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

Hypereosinophilic Syndrome and Clonal Eosinophilia: Point-of-Care Diagnostic Algorithm and Treatment Update

Contact Info

Product

Resources

About