Association between Hasford Scoring System and Hematologic Response in Chronic and Accelerated Phase of Chronic Myelocytic Leukemia Patient with Imatinib for Three Months

Background: Hasford score is a scoring system which was made in interferon treatment era to assess chronic myelocytic leukemia (CML) prognosis. Complete hematologic response (CHR) is the milestone of prognosis evaluation. CHR achievement will significantly increase survival. Imatinib is a revolutionized treatment that change the prognosis of CML. With the advent of Imatinib, lessened the prognostic impact of the Hasford score to predict prognosis.Materials and Methods: An observational analytic with prospective cohort study conducted in oncology outward division Dr. Soetomo hospital Surabaya, from July until October 2018. Hasford score determined in 32 patients at the beginning of the study, given imatinib and followed up regularly for 3 months to know the hematologic response. Data were analyzed using Fisher exact test which was considered significant if p<0.05.Results: Median age was 39 years old, male 37.5% and female 62.5%, the median spleen was 18 cm, median hemoglobin was 9.1 g/dL, median leukocyte was 180x109 /L, median thrombocyte was 645x109 /L, median eosinophil was 2.9%, median basophil was 4.6%, median myeloblast was 6%. Hasford score showed 3.1% in low risk, 25% in intermediate risk and 71.9% in high risk. As much as 78.1% complete hematologic response was found in patient, and 21.9% was incomplete.Conclusion: There was no association between Hasford scoring system and hematologic response in chronic and accelerated phase of chronic myelocytic leukemia patient with imatinib for three month. Hasford score had no impact in hematologic response with imatinib.Keywords: Hasford score, hematologic response, CML, imatini

Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph+ metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P = .0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P = .057 and P = .034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials. (C) 2001 by The American Society of Hematology

An Examination of the life and work of Gustav Hasford

While Stanley Kubrick\u27s film Full Metal Jacket has remained in the national consciousness twenty years after its release, the author of its source material, Gustav Hasford, has not. Few people know or remember that the Oscar-nominated film was not an original work but was adapted by Hasford, Kubrick, and Dispatches author Michael Herr from Hasford\u27s 1979 novel The Short-Timers. Fewer people remember that following the well-reviewed The Short-Timers Hasford published a sequel, The Phantom Blooper, as well as one final novel A Gypsy Good Time, a frenetic parody of detective fiction. To say that Gustav Hasford is primarily remembered as the originator of Full Metal Jacket, or as the owner of the largest library book theft case in United States history, would be inaccurate because Gustav Hasford, for the most part, is not remembered. There are several reasons as to how Gus Hasford came to slip through the cracks of history. For starters, his books have been out of print since 1992, partially because Hasford refused to let The Short-Timers be reprinted under the title of `Full Metal Jacket\u27 and in doing so passed up the chance to reap the financial benefits of added royalties or the exposure another reprinting would have brought him. Additionally, Hasford died at the age of in 1993 at the age of 45, just after his last book was quietly released and with the third book in his planned Vietnam trilogy barely started. The eccentric Hasford found it difficult when alive to retain goodwill amongst either the literary or film communities, feuding with publishers and directors alike. After his death, with his literary career cut short and disgruntled publishers in no mind to market or reprint his books, Hasford fell almost entirely into the oblivion of public memory, both his work and his life essentially forgotten. For my Master\u27s Thesis I propose a study both of Hasford\u27s life and his work for the purpose of shedding light on a talented but forgotten author. No extensive biographical study of Hasford has been attempted since the obituaries that followed his death in 1993, and scholarly examination of his literature has been limited to a few scattered book reviews and a short overview of Hasford\u27s work by his cousin/de facto literary executor. I intend to examine Hasford\u27s life, which included amongst other highlights a tour as a marine combat correspondent, a stint in jail following the largest library fine ever assessed, several weeks spent living on Harlan Ellison\u27s couch, a sophomore novel he would send to book reviewers inscribed with a proclamation that the work was Dead on Arrival because his editor had ruined it, and a personality so tempestuous that it led legendarily difficult-to-work-with Stanley Kubrick to eventually throw up his hands and insist that Hasford was a man HE could not deal with. Additionally I will undertake a critical examination of the key themes running through the two books in his unfinished Vietnam Trilogy, The Short-Timers and The Phantom Blooper, as well as the related biographical undertones in A Gypsy Good Time, for all intents and purposes the unintended ending to that trilogy. It is hoped that through my research some long-overdue critical attention will be paid both to Hasford\u27s novels and to Hasford himself so that he can begin to be recognized as the key contributor to Vietnam War fiction that he was

Combined population dynamics and entropy modelling supports patient stratification in chronic myeloid leukemia

Modelling the parameters of multistep carcinogenesis is key for a better understanding of cancer progression, biomarker identification and the design of individualized therapies. Using chronic myeloid leukemia (CML) as a paradigm for hierarchical disease evolution we show that combined population dynamic modelling and CML patient biopsy genomic analysis enables patient stratification at unprecedented resolution. Linking CD34+ similarity as a disease progression marker to patientderived gene expression entropy separated established CML progression stages and uncovered additional heterogeneity within disease stages. Importantly, our patient data informed model enables quantitative approximation of individual patients’ disease history within chronic phase (CP) and significantly separates “early” from “late” CP. Our findings provide a novel rationale for personalized and genome-informed disease progression risk assessment that is independent and complementary to conventional measures of CML disease burden and prognosis

Korelasi Skor Hasford dengan Respons Terapi Imatinib mesylate Pada Pasien Leukemia Granulositik Kronik

Latar Belakang: Tujuan terapi leukemia granulositik kronis adalah tercapainya Latar Belakang: Tujuan terapi leukemia granulositik kronis adalah tercapainya remisi komplit, baik remisi hematologi, sitogenetika, maupun molekuler. Sistem prognostik diperlukan dalam membantu memilih terapi secara efisien, salah satunya adalah skor Hasford. Penelitian ini dilakukan untuk melihat korelasi skor Hasford dengan respons terapi Imatinib mesylate pada pasien LGK di kota Malang. Metode: Penelitian ini dilakukan dengan metode survei. Data diambil secara retrospektif berdasarkan rekam medis. Populasi adalah pasien LGK fase kronis yang menerima terapi Imatinib mesylate sekurang-kurangnya 18 bulan di Instalasi Rawat Jalan RSUD Saiful Anwar Malang. Penghitungan skor Hasford dilakukan dengan menggunakan data saat pertama kali pasien menerima Imatinib. Hasil penelitian disajikan secara deskriptif serta dianalisis secara korelasi. Analisis respons terapi dilakukan dengan Uji Chi Square, sedangkan penilaian resistensi dilakukan dengan luas kurva ROC. Hasil: Pada penelitian ini, didapatkan 51 pasien dengan 2 pasien berada di skor Hasford risiko rendah, 20 pasien risiko sedang dan 29 pasien risiko tinggi. Korelasi bermakna didapatkan pada respons hematologi pada bulan ketiga dan keenam (p masing-masing 0.040, 0.020), serta pada respons molekuler pada bulan kedua belas (p=0.049). Resistensi Imatinib mesylate dapat diperkirakan dengan skor Hasford dengan luas kurva ROC sebesar 0.811 dan 95% CI sebesar 0.613 - 1.009 (p=0.014). Cut of value dalam menentukan resisten atau non-resisten terhadap Imatinib adalah 1284.338, di mana skor Hasford < 1284.338 termasuk dalam kategori non-resisten dan sebaliknya. Kesimpulan: Skor Hasford berkorelasi terhadap respons hematologi dan molekuler pada pasien LGK yang diterapi Imatinib mesylate serta kemungkinan resistensi terhadap agen tersebu

Correlation between Hasford Score with Early Molecular Response in Patients with Chronic Myeloid Leukemia in Chronic Phase Treated with Imatinib

The aim of the study is to to determine correlation Hasford score and early molecular response in chronic phase BCR-ABL-Positive CML patients treated with imatinib. This is an longitudinal observational study in newly diagnosed patients of CML chronic phase BCR-ABL-Positive treated imatinib from Januari 2017 to September 2017. Patients were stratified according to Hasford score at diagnosis. Q-PCR(Quantitative RT-PCR) were used to monitor BCR-ABL transcription levels after 3 months of imatinib treatment. Correlation between Hasford score with early molecular response were analyzed using Koefisien Kontingensi’s correlation test. Results: Thirty five patients were enrolled in this study consist of 13 male and 22 female. After 3 months of imatinib treatment, EMR were 5 patients (83.3%), 11 patients (61.1%) and 2 patients (18.2%) in low, intermediate, and high risk group patients, respectively. Koefisien kontigensi test showed that there was significant correlation between Hasford score and EMR (p=0.018; r=0.431). The Hasford score correlated to early molecular response in chronic phase BCR-ABL-positive CML patients received imatinib

Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34+/CD38─ CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4+ SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26+ LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26+ CML LSC engrafted NOD-SCID-IL-2Rγ−/− (NSG) mice with BCR/ABL1+ cells, whereas CD26─ SC from the same patients produced multilineage BCR/ABL1– engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1+ cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy