FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1987362309> ?p ?o ?g. }

• W1987362309 endingPage "645" @default.
• W1987362309 startingPage "643" @default.
• W1987362309 abstract "Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare disorder with hypereosinophilia and an increased number of blood or marrow blast (<20%) or an evidence of eosinophil clonality. We evaluated the clinical outcome of 10 patients with CEL-NOS. Seven males and three females at a median age of 62 years (range, 23–73) were included. The median leukocyte count at diagnosis was 33.4 × 109/l (range, 9.3–175.0) with a median eosinophil count of 15.6 × 109/l (range, 1.5–136.0). Median hemoglobin and platelets were 11.0 g/dl (range, 8.3–13.3) and 158 × 109/l (range, 31.0–891.0), respectively. Clinical manifestations included splenomegaly (n = 7), hepatomegaly (n = 6), cardiac failure (n = 2), and lung infiltrations (n = 1). Median survival from diagnosis to death for entire cohort was 22.2 months (range, 2.2–186.2). Five of the 10 studied patients developed acute transformation (AT) after median of 20 months from diagnosis (range, 1.6–41.9). None of patients with AT is alive at the time of last follow-up. Median time from AT to death was 2 months (range, 1.0–6.1). Among five patients who did not develop AT, three died in active disease. Two patients are alive in complete remission; first underwent allogeneic stem-cell transplantation preceding by intensive induction chemotherapy; the second remains on imatinib with hydroxyurea. Except the latter patient, imatinib was ineffective in our study population. CEL-NOS is a rare and aggressive disease with high rate of AT and resistance to conventional treatment. Chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) is a rare Philadelphia-negative myeloproliferative neoplasm, which is due to clonal proliferation of eosinophil precursors. Peripheral blood hypereosinophilia (>1.5 × 109/l), an increased number of myeloblasts in blood or marrow (<20%) or an evidence of eosinophil clonality, are required for diagnosis. The cases of myeloid and lymphoid neoplasms with abnormalities of platelet-derived growth factor alpha (PDGFRA), platelet-derived growth factor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) must be also excluded [1]. In a new WHO classification, CEL-NOS is listed in the category of myeloproliferative neoplasms [2], whereas it was incorporated under the heading of myeloproliferative forms of hypereosinophilic syndromes according to the classification of the Eosinophilic Working Group [3]. Regardless of the classification used, CEL-NOS remains an extremely rare entity with variable prognosis [1, 4]. The efficacy of currently used therapeutic agents is limited, and the hematological responses are usually short-lived [5]. Ten patients (seven males and three females) at a median age of 62 years (range, 23–73) were included in this study. The median leukocyte count at diagnosis was 33.4 × 109/l with a median eosinophil count of 15.6 × 109/l. Blood smear was dominated by mature eosinophils with a small number of younger forms, for example, eosinophilic myelocytes and promyelocytes. Single eosinophils had dysplastic features. Median proportions of blood and marrow blast cells at diagnosis were 5 (range, 1–10%) and 9% (range, 6–15%), respectively. Bone marrow trephine biopsy was done in six patients at diagnosis. Median cellularity was 90% (range, 80–100%), and there was fibrosis of grade 1 in all studied cases. No increased number of mast cells was noted using tryptase staining. Details on patient characteristics at diagnosis were shown in Table I. Constitutional symptoms including weight loss, night sweating, persistent cough, pruritus, progressive weakness, and diarrhea were found in four patients. Organ involvement was as follows: splenomegaly (n = 7), hepatomegaly (n = 6), cardiac failure (n = 2), and lung infiltrations (n = 1). The results of cytogenetic studies were available for 8 of the 10 patients at chronic phase (CP): normal diploid karyotype was found in six patients and loss of chromosome 7 in one. Two patients had no metaphases, and in one case, the study was not done. At CP, patients most frequently received corticosteroids (n = 7); hydroxyurea (n = 9) and imatinib (n = 5). Median survival from diagnosis to death for entire cohort was 22.2 months (range, 2.2–186.2 months; see Fig. 1). Overall survival for entire CEL-NOS cohort. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] Five of the 10 studied patients developed AT after median of 20 months from diagnosis (range, 1.6–41.9). There were four cases of secondary acute myeloid leukemia (M4, n = 3; M5, n = 1) and 1 patient had T-cell lymphoblastic leukemia/lymphoma. All patients were negative for RUNX1/RUNX1T1, CBFβ/MYH11, and FLT3-ITD. Details on the results of cytogenetic studies and treatment for patients at AT were presented in Table II. Comparison between CEL-NOS patients without and with blast crisis revealed significant elevated leukocyte count (121 × 109/l vs. 14 × 109/l; P = 0.01) and eosinophil count (46.5 × 109/l vs. 2.8 × 109/l; P = 0.02) in the former group. None of patients with AT is alive at the time of last follow-up. These patients were treated with more intensive chemotherapy but eventually died from resistant disease or chemotherapy-associated complications. Median time from AT onset to death was 2 months (range, 1.0–6.1 months). Among five patients who did not develop AT, three died in active disease, whereas two are still alive in complete remission (CR). One young male was treated with intensive induction chemotherapy and achieved CR. He was transplanted from sibling donor and remained free of disease 15 years after transplant. In a second case, CR was achieved after combination of hydroxyurea with imatinib. CEL-NOS constitutes a new entity within WHO classification [2]. It seems to be rare disorder, and its true incidence is unknown. Recently reported study using the Surveillance, Epidemiology, and End Results results in an incidence of 0.036 per 100,000 person-years, but this calculation comprised patients with HES including CEL [4]. We should keep in mind that CEL has been previously lumped together with idiopathic HES. Moreover, many patients, who have been classified as idiopathic HES, can now be found to have a FIP1L1-PDGFRA (F/P) fusion transcript [6]. Because of this ambiguity, it is extremely difficult to draw conclusions about clinical manifestations, therapeutic strategies, and prognosis in patients with CEL-NOS. Currently, our knowledge about this disorder results from literature-described case reports presenting patients with different chromosomal abnormalities [7]. Herein, we provided details on clinical characteristics of CEL-NOS patients, and our data were based on the largest group studied so far. We found that patients with CEL-NOS were predominantly male (70%), and splenomegaly (70%) was the most frequent clinical manifestation. These findings were consistent with the results reported for F/P-positive CEL patients [8, 9]. We attempted to compare the results of blood tests, which have been reported for F/P-positive CEL patients by two large European groups [8, 10] with those provided in this study. We demonstrated almost threefold higher number of median leukocyte and eosinophil counts at diagnosis in the latter cohort. Of note is that prognosis is completely different. The response rate is close to100% in the F/P-positive CEL population. It is due to extremely high sensitivity of the F/P fusion transcript to low dose of imatinib [9, 10]. Many chromosomal abnormalities were detected in eosinophilic leukemias, but the most common was trisomy of chromosome 8 [7]. It should be underscored that majority of chromosomal rearrangements were described in single patients, in a CP of their disease. The results of cytogenetic analysis were available for seven patients at diagnosis in our study group. There was predominance of normal diploid karyotype. Only one patient had chromosomal abnormality—monosomy 7. The loss of chromosome 7 was previously described in a patient with hypereosinophilia [11]. After median of 20 months from initial diagnosis, 50% of study patients had AT; there were four cases of acute myeloid leukemias and one patient transformed into T-cell lymphoblastic leukemia/lymphoma. All cases were fatal after median of 2 months from AT diagnosis. The results of cytogenetic studies were provided for all transformed cases. In a male patient with previously described monosomy of chromosome 7, this abnormality was detected again at AT. Time from CP to AT was very short (<2 months) as well as interval from AT onset to death (∼1 month). It was well documented that monosomy 7 is an indicator of very poor prognosis in AML with an estimated 4-year overall survival of 4% [12]. Chromosomal abnormalities detected in the remaining three patients have already been described in patients with CEL, both as a single abnormality or as a part of a complex karyotype [13-15]. At least one of this finding was associated with AT [14]. One of our patients was found to have yet undefined chromosomal rearrangement—t(2;4)(p13;p15); 43, XY, −17,−18,−22. Chromosomal abnormality presenting similar translocation but involving different breakpoints was identified recently, and it was found to be highly imatinib-sensitive with long-term clinical response [16]. Cases with CEL-NOS are characterized by aggressive clinical course, and they are usually unresponsive to conventional chemotherapy [5]. Our experience with 10 patients seems to confirm this observation. Median survival for entire cohort slightly exceeded 20 months. Because of small number of reported patients, it is extremely difficult to propose therapeutic schema. We may conclude that corticosteroids are useless in CEL-NOS. In our study, cohort corticosteroids were initially given in seven patients, but they were started in Out-Clinic setting in order to decrease eosinophil count before the final diagnosis was established. Hydroxyurea remains a reasonable first-line option, and it was used in 90% of our patients with different efficacy. In one male patient from our cohort, combination of hydroxyurea with imatinib resulted in CR of long-term duration. Interferon α (IFN) is found to be effective in some hydroxyurea-resistant patients [17]. Single case reports showed encouraging responses to IFN in terms of disease control, and some patients even experienced cytogenetic remission [18]. It seems rationale to attempt a short course of imatinib at higher dose (>400 mg/daily) in some resistant CEL-NOS cases just as it was demonstrated for F/P-negative HES subgroup [8]. The role of transplantation in CEL-NOS is not well established; our current experience is based on single case reports [19]. On the other hand, as it was documented in our study, allogeneic stem-cell transplantation seems to be only curative option for this intractable ill patient. The resistance to conventionally used agents and high risk of acute transformation (AT) should incline us to administer an intensive AML-like chemotherapy and proceed fit patients to transplant procedure. Unfortunately, most patients with CEL-NOS are at advanced age and have significant comorbidities. In conclusion, CEL-NOS is a rare and aggressive disease with high rate of AT and resistant to conventional treatment. It is difficult to draw final conclusions about clinical outcome due to low number of patients. Moreover, most CEL-NOS cases were previously classified within HES population, and some of them were found to have F/P transcript. It seems reasonable to initiate multicenter efforts to collect larger clinical data and attempt to define patients with the highest risk of AT. Allogeneic stem-cell transplantation remains only curative option for younger and fit patients with CEL-NOS. Clinical trial with novel investigational agents is highly recommended. One hundred and eight patients with prolonged, nonreactive blood hypereosinophilia were seen in our department between 1996 and 2011. The diagnosis was following: Churg–Strauss syndrome (n = 2), benign idiopathic hypereosinophilia (n = 8), idiopathic HES (n = 58), lymphocytic variant of HES (n = 4), F/P-positive CEL (n = 26), and CEL-NOS (n = 10). Blood tests, standard biochemical panel, and bone marrow assessment were performed at baseline. Additional studies included the measurement of serum IgE, vitamin B12, and interleukin-5 levels. All reactive causes of hypereosinophilia were carefully excluded. Imaging studies included chest X-ray and abdominal ultrasound. Chromosomes were analyzed with conventional G-banding technique after 48 hr stimulation with granulocyte colony-stimulating factor. The minimal required number of metaphases was 30, and chromosomes were described according to the International System for Cytogenetic Nomenclature [20]. The FIP1L1-PDGFRA fusion gene was revealed by nested PCR as described previously [6]. The JAK2V617F point mutation was detected using commercially available kit MutaScreen™ (Ipsogen, Marseille, France). Peripheral blood T-lymphocytes were analyzed by standard flow cytometric technique using a panel of monoclonal antibodies against the lineage-associated T-cell markers. Serum tryptase levels were measured using UniCAP tryptase fluoroenzymeimmunoassay (Pharmacia, Uppsala, Sweden). A diagnosis of AT required peripheral blood and/or bone marrow blasts to be greater than 20%. The French-American-British classification categorized the leukemic cells [21], and WHO classification was used to classify the precursor lymphoid neoplasms [22]. All study patients were negative for BCR-ABL, FIP1L1-PDGFRA, and JAK2V61F mutations. There were no patients with involvement of chromosomes bands 5q31-33 (PDGFRB) or 8p11 (FGFR1). Lymphocytic variant of hypereosinophilia was excluded by flow cytometry. CHR required a normal white blood cell count with a total eosinophil count of less than 0.7 × 109/L and complete resolution of organ involvement for more than 1 months. Nonparametric comparisons of group means were performed by using the Mann–Whitney U test. Proportions were compared by Fisher exact test. The distribution for overall survival was estimated using the method of Kaplan and Meier. A P value less than 0.05 were considered significant. All computations were performed with StatSoft Poland analysis software (version 10.0). GH was responsible for all phases of the manuscript preparation and submission. AS and ABC performed molecular and cytogenetic studies. SKK was responsible for critical inputs and review of the draft and final version of the manuscript. Grzegorz Helbig*, Anna Soja*, Aleksandra Bartkowska-Chrobok*, Sławomira Kyrcz-Krzemień*, * Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland." @default.
• W1987362309 created "2016-06-24" @default.
• W1987362309 creator A5010133674 @default.
• W1987362309 creator A5057342680 @default.
• W1987362309 creator A5062207538 @default.
• W1987362309 creator A5066841197 @default.
• W1987362309 date "2012-03-31" @default.
• W1987362309 modified "2023-10-06" @default.
• W1987362309 title "Chronic eosinophilic leukemia-not otherwise specified has a poor prognosis with unresponsiveness to conventional treatment and high risk of acute transformation" @default.
• W1987362309 cites W1605230984 @default.
• W1987362309 cites W1811953845 @default.
• W1987362309 cites W1965594055 @default.
• W1987362309 cites W2006236202 @default.
• W1987362309 cites W2006397845 @default.
• W1987362309 cites W2010187130 @default.
• W1987362309 cites W2012952884 @default.
• W1987362309 cites W2032742505 @default.
• W1987362309 cites W2036047439 @default.
• W1987362309 cites W2045528146 @default.
• W1987362309 cites W2053597373 @default.
• W1987362309 cites W2068158468 @default.
• W1987362309 cites W2076426515 @default.
• W1987362309 cites W2094849429 @default.
• W1987362309 cites W2117446917 @default.
• W1987362309 cites W2155591233 @default.
• W1987362309 cites W2161167886 @default.
• W1987362309 cites W2163318259 @default.
• W1987362309 cites W2319145348 @default.
• W1987362309 cites W2339359539 @default.
• W1987362309 cites W2473792341 @default.
• W1987362309 doi "https://doi.org/10.1002/ajh.23193" @default.
• W1987362309 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22473587" @default.
• W1987362309 hasPublicationYear "2012" @default.
• W1987362309 type Work @default.
• W1987362309 sameAs 1987362309 @default.
• W1987362309 citedByCount "61" @default.
• W1987362309 countsByYear W19873623092012 @default.
• W1987362309 countsByYear W19873623092013 @default.
• W1987362309 countsByYear W19873623092014 @default.
• W1987362309 countsByYear W19873623092015 @default.
• W1987362309 countsByYear W19873623092016 @default.
• W1987362309 countsByYear W19873623092017 @default.
• W1987362309 countsByYear W19873623092018 @default.
• W1987362309 countsByYear W19873623092019 @default.
• W1987362309 countsByYear W19873623092020 @default.
• W1987362309 countsByYear W19873623092021 @default.
• W1987362309 countsByYear W19873623092022 @default.
• W1987362309 countsByYear W19873623092023 @default.
• W1987362309 crossrefType "journal-article" @default.
• W1987362309 hasAuthorship W1987362309A5010133674 @default.
• W1987362309 hasAuthorship W1987362309A5057342680 @default.
• W1987362309 hasAuthorship W1987362309A5062207538 @default.
• W1987362309 hasAuthorship W1987362309A5066841197 @default.
• W1987362309 hasBestOaLocation W19873623091 @default.
• W1987362309 hasConcept C104317684 @default.
• W1987362309 hasConcept C126322002 @default.
• W1987362309 hasConcept C203014093 @default.
• W1987362309 hasConcept C204241405 @default.
• W1987362309 hasConcept C2778461978 @default.
• W1987362309 hasConcept C54355233 @default.
• W1987362309 hasConcept C71924100 @default.
• W1987362309 hasConcept C86803240 @default.
• W1987362309 hasConceptScore W1987362309C104317684 @default.
• W1987362309 hasConceptScore W1987362309C126322002 @default.
• W1987362309 hasConceptScore W1987362309C203014093 @default.
• W1987362309 hasConceptScore W1987362309C204241405 @default.
• W1987362309 hasConceptScore W1987362309C2778461978 @default.
• W1987362309 hasConceptScore W1987362309C54355233 @default.
• W1987362309 hasConceptScore W1987362309C71924100 @default.
• W1987362309 hasConceptScore W1987362309C86803240 @default.
• W1987362309 hasIssue "6" @default.
• W1987362309 hasLocation W19873623091 @default.
• W1987362309 hasLocation W19873623092 @default.
• W1987362309 hasOpenAccess W1987362309 @default.
• W1987362309 hasPrimaryLocation W19873623091 @default.
• W1987362309 hasRelatedWork W1506200166 @default.
• W1987362309 hasRelatedWork W1995515455 @default.
• W1987362309 hasRelatedWork W2048182022 @default.
• W1987362309 hasRelatedWork W2080531066 @default.
• W1987362309 hasRelatedWork W2604872355 @default.
• W1987362309 hasRelatedWork W2748952813 @default.
• W1987362309 hasRelatedWork W2899084033 @default.
• W1987362309 hasRelatedWork W3031052312 @default.
• W1987362309 hasRelatedWork W3032375762 @default.
• W1987362309 hasRelatedWork W3108674512 @default.
• W1987362309 hasVolume "87" @default.
• W1987362309 isParatext "false" @default.
• W1987362309 isRetracted "false" @default.
• W1987362309 magId "1987362309" @default.
• W1987362309 workType "article" @default.