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  1. NTU Theses and Dissertations Repository
  2. 生物資源暨農學院
  3. 獸醫專業學院
  4. 獸醫學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93467
完整後設資料紀錄
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dc.contributor.advisor王尚麟zh_TW
dc.contributor.advisorShang-Lin Wangen
dc.contributor.author林怡甄zh_TW
dc.contributor.authorYi-Chen Linen
dc.date.accessioned2024-08-01T16:16:50Z-
dc.date.available2024-08-02-
dc.date.copyright2024-08-01-
dc.date.issued2024-
dc.date.submitted2024-07-10-
dc.identifier.citation1. Ito D, Frantz AM, Modiano JF. Canine lymphoma as a comparative model for human non-Hodgkin lymphoma: recent progress and applications. Veterinary Immunology and Immunopathology. 2014;159(3-4):192-201.
2. Mahiddine FY, You I, Park H, Kim MJ. Microbiome Profile of Dogs with Stage IV Multicentric Lymphoma: A Pilot Study. Veterinary Sciences. 2022;9(8):409.
3. Ponce F, Marchal T, Magnol JP, Turinelli V, Ledieu D, Bonnefont C, et al. A morphological study of 608 cases of canine malignant lymphoma in France with a focus on comparative similarities between canine and human lymphoma morphology. Veterinary Pathology. 2010;47(3):414-33.
4. Sözmen M, Tasca S, Carli E, Lorenzi DD, Furlanello T, Caldin M. Use of Fine Needle Aspirates and Flow Cytometry for the Diagnosis, Classification, and Immunophenotyping of Canine Lymphomas. Journal of Veterinary Diagnostic Investigation. 2005;17(4):323-9.
5. Ernst T, Kessler M, Lautscham E, Willimzig L, Neiger R. Multicentric lymphoma in 411 dogs - an epidemiological study. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2016;44(4):245-51.
6. Moore AS, Frimberger AE. Usefulness of chemotherapy for the treatment of very elderly dogs with multicentric lymphoma. Journal of the American Veterinary Medical Association. 2018;252(7):852-9.
7. Mutsaers AJ, Glickman NW, Denicola DB, Widmer WR, Bonney PL, Hahn KA, et al. Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alone for multicentric lymphoma in dogs. Journal of the American Veterinary Medical Association. 2002;220(12):1813-7.
8. Al-Nadaf S, Rebhun RB, Curran KM, Venable RO, Skorupski KA, Willcox JL, et al. Retrospective analysis of doxorubicin and prednisone as first-line therapy for canine B-cell lymphoma. BMC Veterinary Research. 2018;14(1).
9. Keller ET, Macewen EG, Rosenthal RC, Helfand SC, Fox LE. Evaluation of Prognostic Factors and Sequential Combination Chemotherapy With Doxorubicin for Canine Lymphoma. Journal of Veterinary Internal Medicine. 1993;7(5):289-95.
10. Garrett LD, Thamm DH, Chun R, Dudley R, Vail DM. Evaluation of a 6‐Month Chemotherapy Protocol with No Maintenance Therapy for Dogs with Lymphoma. Journal of Veterinary Internal Medicine. 2002;16(6):704-9.
11. Hosoya K, Kisseberth WC, Lord LK, Alvarez FJ, Lara‐Garcia A, Kosarek CE, et al. Comparison of COAP and UW‐19 Protocols for Dogs with Multicentric Lymphoma. Journal of Veterinary Internal Medicine. 2007;21(6):1355-63.
12. Egler RA, Ahuja SP, Matloub Y. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. Journal of Pharmacology and Pharmacotherapeutics. 2016;7(2):62-71.
13. Jeffreys AB, Knapp DW, Carlton WW, Thomas RM, Bonney PL, Degortari A, et al. Influence of Asparaginase on a Combination Chemotherapy Protocol for Canine Multicentric Lymphoma. Journal of the American Animal Hospital Association. 2005;41(4):221-6.
14. Lee JJ, Liao AT, Wang SL. L-Asparaginase, Doxorubicin, Vincristine, and Prednisolone (LHOP) Chemotherapy as a First-Line Treatment for Dogs with Multicentric Lymphoma. Animals. 2021;11(8):2199.
15. Nakagawa T, Kojima M, Ohno K, Chambers JK, Uchida K, Ohmi A, et al. Efficacy and adverse events of continuous l‐asparaginase administration for canine large cell lymphoma of presumed gastrointestinal origin. Veterinary and Comparative Oncology. 2022;20(1):102-8.
16. Asselin B, Rizzari C. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring. Leukemia & Lymphoma. 2015;56(8):2273-80.
17. Blake MK, Carr BJ, Mauldin GE. Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012. The Canadian Veterinary Journal. 2016;57(2):176-82.
18. Wright Z, Steiner J, Suchodolski J, Rogers K, Barton C, Brown M. A pilot study evaluating changes in pancreatic lipase immunoreactivity concentrations in canines treated with L-asparaginase (ASNase), vincristine, or both for lymphoma. Canadian Journal of Veterinary Research. 2009;73(2):103-10.
19. Lautscham EM, Kessler M, Ernst T, Willimzig L, Neiger R. Comparison of a CHOP‐LAsp‐based protocol with and without maintenance for canine multicentric lymphoma. Veterinary Record. 2017;180(12):303-.
20. Mellanby RJ, Herrtage ME, Dobson JM. Owners' assessments of their dog's quality of life during palliative chemotherapy for lymphoma. Journal of Small Animal Practice. 2003;44(3):100-3.
21. Curran K, Thamm DH. Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15‐week, maintenance‐free CHOP protocol. Veterinary and Comparative Oncology. 2016;14(S1):147-55.
22. Simon D, Nolte I, Eberle N, Abbrederis N, Killich M, Hirschberger J. Treatment of Dogs with Lymphoma Using a 12‐Week, Maintenance‐Free Combination Chemotherapy Protocol. Journal of Veterinary Internal Medicine. 2006;20(4):948-54.
23. Vos N, Pellin M, Vail DM. A comparison of 12- and 19-week CHOP protocols using non-randomized, contemporaneous controls. Veterinary and Comparative Oncology. 2019;17(3):276-84.
24. Długosz-Danecka M, Szmit S, Ogórka T, Skotnicki AB, Jurczak W. The average relative dose intensity of R-CHOP is an independent factor determining favorable overall survival in diffuse large B-cell lymphoma patients. Cancer Medicine. 2019;8(3):1103-9.
25. Gregory SA, Trümper L. Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes? Annals of Oncology. 2005;16(9):1413-24.
26. Chun R, Garrett LD, Vail DM. Evaluation of a High‐Dose Chemotherapy Protocol with No Maintenance Therapy for Dogs with Lymphoma. Journal of Veterinary Internal Medicine. 2000;14(2):120-4.
27. Burton JH, Garrett-Mayer E, Thamm DH. Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma. Veterinary and Comparative Oncology. 2013;11(4):306-15.
28. Korkmaz A, Topal T, Oter S. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation. Cell Biology and Toxicology. 2007;23(5):303-12.
29. Sato M, Yamazaki J, Goto‐Koshino Y, Takahashi M, Fujino Y, Ohno K, et al. Evaluation of Cytoreductive Efficacy of Vincristine, Cyclophosphamide, and Doxorubicin in Dogs with Lymphoma by Measuring the Number of Neoplastic Lymphoid Cells with Real‐Time Polymerase Chain Reaction. Journal of Veterinary Internal Medicine. 2011;25(2):285-91.
30. Wang SL, Lee JJ, Liao AT. Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link? The Veterinary Journal. 2016;213:87-9.
31. Valerius KD, Ogilvie GK, Fettman MJ, Walton JA, Richardson K, Powers BE, et al. Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin. Journal of the American Veterinary Medical Association. 1999;214(3):353-6.
32. Sapierzyński R, Kliczkowska-Klarowicz K, Jankowska U, Jagielski D. Cytodiagnostics of canine lymphomas – possibilities and limitations. Polish Journal of Veterinary Sciences. 2016;19(2):433-9.
33. Owen LN, Organization WH. TNM Classification of Tumours in Domestic Animals/edited by LN Owen. World Health Organization; 1980.
34. Wilkerson MJ, Dolce K, Koopman T, Shuman W, Chun R, Garrett L, et al. Lineage differentiation of canine lymphoma/leukemias and aberrant expression of CD molecules. Veterinary Immunology and Immunopathology. 2005;106(3-4):179-96.
35. Adam F, Villiers E, Watson S, Coyne K, Blackwood L. Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukaemia. Veterinary and Comparative Oncology. 2009;7(3):181-95.
36. Vail DM, Michels GM, Khanna C, Selting KA, London CA. Response evaluation criteria for peripheral nodal lymphoma in dogs (v1.0)-a veterinary cooperative oncology group (VCOG) consensus document. Veterinary and Comparative Oncology. 2010;8(1):28-37.
37. Wang SL, Lee JJ, Liao AT. Comparison of efficacy and toxicity of doxorubicin and mitoxantrone in combination chemotherapy for canine lymphoma. The Canadian Veterinary Journal. 2016;57(3):271-6.
38. Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, Mcleod H, Klein TE, et al. Doxorubicin pathways. Pharmacogenetics and Genomics. 2011;21(7):440-6.
39. Montgomery B, Lin DW. Toxicities of chemotherapy for genitourinary malignancies. Complications of Urologic Surgery: Elsevier; 2010. p. 117-23.
40. Mauldin GE, Fox PR, Patnaik AK, Bond BR, Mooney SC, Matus RE. Doxorubicin‐lnduced Cardiotoxicosis Clinical Features in 32 Dogs. Journal of Veterinary Internal Medicine. 1992;6(2):82-8.
41. Saba CF, Hafeman SD, Vail DM, Thamm DH. Combination Chemotherapy with Continuous l‐Asparaginase, Lomustine, and Prednisone for Relapsed Canine Lymphoma. Journal of Veterinary Internal Medicine. 2009;23(5):1058-63.
42. Moore AS, London CA, Wood CA, Williams LE, Cotter SM, L'Heureux DA, et al. Lomustine (CCNU) for the Treatment of Resistant Lymphoma in Dogs. Journal of Veterinary Internal Medicine. 1999;13(5):395-8.
43. Damia G, D'Incalci M. Mechanisms of resistance to alkylating agents. Cytotechnology. 1998;27(1/3):165-73.
44. Setthawongsin C, Teewasutrakul P, Tangkawattana S, Techangamsuwan S, Rungsipipat A. Conventional-Vincristine Sulfate vs. Modified Protocol of Vincristine Sulfate and L-Asparaginase in Canine Transmissible Venereal Tumor. Frontiers in Veterinary Science. 2019;6.
45. Kidd JA, Ross P, Buntzman AS, Hess PR. Development of an ELISA to detect circulating anti-asparaginase antibodies in dogs with lymphoid neoplasia treated with Escherichia coli l-asparaginase. Veterinary and Comparative Oncology. 2015;13(2):77-88.
46. Woo M, Hak L, Storm M, Evans W, Sandlund J, Rivera G, et al. Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia. Leukemia. 1998;12(10):1527-33.
47. Lee KW, Kim DY, Yun T, Kim DW, Kim TY, Yoon SS, et al. Doxorubicin‐based chemotherapy for diffuse large B‐cell lymphoma in elderly patients. Cancer. 2003;98(12):2651-6.
48. Frimberger AE, Moore AS, Rassnick KM, Cotter SM, O'Sullivan JL, Quesenberry PJ. A combination chemotherapy protocol with dose intensification and autologous bone marrow transplant (VELCAP-HDC) for canine lymphoma. Journal of Veterinary Internal Medicine. 2006;20(2):355-64.
49. Frank JD, Reimer SB, Kass PH, Kiupel M. Clinical Outcomes of 30 Cases (1997–2004) of Canine Gastrointestinal Lymphoma. Journal of the American Animal Hospital Association. 2007;43(6):313-21.
50. Rassnick KM, Moore AS, Collister KE, Northrup NC, Kristal O, Chretin JD, et al. Efficacy of Combination Chemotherapy for Treatment of Gastrointestinal Lymphoma in Dogs. Journal of Veterinary Internal Medicine. 2009;23(2):317-22.
51. Goodman IH, Moore AS, Frimberger AE. Treatment of canine non-indolent T cell lymphoma using the VELCAP-TSC protocol: A retrospective evaluation of 70 dogs (2003-2013). The Veterinary Journal. 2016;211:39-44.
52. Piek CJ, Putteman GR, Teske E. Evaluation of the results of a L‐asparaginase‐based continuous chemotherapy protocol versus a short doxorubicin‐based induction chemotherapy protocol in dogs with malignant lymphoma. Veterinary Quarterly. 1999;21(2):44-9.
53. Valerius KD, Ogilvie GK, Fettman MJ, Walton JA, Richardson K, Powers BE, et al. Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin. Journal of the American Veterinary Medical Association. 1999;214(3):353-6.
54. Zalewska-Szewczyk B, Andrzejewski W, Młynarski W, Jedrychowska-Dańska K, Witas H, Bodalski J. The anti-asparagines antibodies correlate with L-asparagines activity and may affect clinical outcome of childhood acute lymphoblastic leukemia. Leukemia & Lymphoma. 2007;48(5):931-6.
55. Albertsen BK, Schrøder H, Jakobsen P, Müller HJ, Carlsen NT, Schmiegelow K. Monitoring of Erwinia asparaginase therapy in childhood ALL in the Nordic countries. British Journal of Clinical Pharmacology. 2001;52(4):433-7.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93467-
dc.description.abstract多中心型淋巴癌是犬隻最常見的惡性腫瘤,若不進行任何治療,存活時間可能不到六週。目前在小動物的淋巴癌治療上,主要是以CHOP (C,環磷酰胺;H,阿黴素;O,長春新鹼和P,類固醇)化療療程為基底的誘導治療。這個治療療程當中包含了四個週期的療程。獸醫師藉由縮短治療週期和搭配不一樣的藥物,希望能減少治療的花費和增加犬隻的生活品質。CHOP化療療程為基底的化療從25週逐漸縮減成15週都有相似的治療效果。
在這項研究中,我們將19週的LHOP (L,天冬酰胺酶;H,阿黴素;O,長春新鹼和P,類固醇)化療療程縮短成15週希望能讓動物的生活品質更好和減少飼主的花費。然而在縮短治療時間減少了四次vincristine投予之後,結果顯示,縮短後的治療有統計上顯著較差的疾病無進展生存時間(p=0.006)和生存時間(p=0.018)。在15週LHOP化療療程和19週LHOP化療療程的中位疾病無進展生存時間分別為265天和401天,而中位存活時間分別為420天和530天。而兩組在年紀(p=0.851)、體重(p=0.934)、性別(p=0.093)、臨床分期(p=0.448)、亞分期(p=0.396)、免疫表型(p=0.344)、和總血清鈣(p=0.474)在統計上都沒有顯著差異。因此不建議將19週LHOP化療療程縮短為15週LHOP。
zh_TW
dc.description.abstractLymphoma is the most common malignant tumor in dogs. Without therapy, dogs with lymphoma may survive less than 6 weeks. In current clinical practice, the majority of veterinarians utilize a CHOP-based (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisolone) chemotherapy protocol as an induction protocol to treat lymphoma. This protocol includes four cycles. To reduce costs and improve the quality of life for dogs, veterinarians have attempted to shorten the chemotherapy protocol and combine different drugs. The CHOP protocol shortened from 25 weeks to 15 weeks showed similar efficacy.
In our study, we shortened the 19-week LHOP (L, L-asparaginase; H, doxorubicin; O, vincristine; and P, prednisolone) to a 15-week LHOP to improve the patient's quality of life and reduce the cost of treatment. However, after omitting four doses of vincristine, the results showed that the 15-week LHOP had worse progression-free survival and overall survival time than the 19-week LHOP, with significant differences, indicated by p-values of 0.006 and 0.018, respectively. The median progression-free survival of the 15-week LHOP and 19-week LHOP were 265 and 401 days, respectively. The median overall survival time of the 15-week LHOP and 19-week LHOP were 420 and 530 days, respectively. No significant differences were found in age (p=0.851), body weight (p=0.934), gender ratio (p=0.093), clinical stage (p=0.448), substage (p=0.396), immunophenotype (p=0.344), and total serum calcium (p=0.474). Therefore, shortening the 19-week LHOP to a 15-week LHOP is not recommended.
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dc.description.provenanceSubmitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-01T16:16:50Z
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dc.description.tableofcontents誌謝 i
中文摘要 iii
ABSTRACT iv
CONTENTS vi
LIST OF FIGURES viii
LIST OF TABLES ix
LIST OF ABBREVIATIONS x
Chapter 1 Introduction 1
Chapter 2 Literature Review 4
2.1 Chemotherapy treatment with or without maintenance 4
2.2 Shortening the multi-drug chemotherapy protocol 5
2.3 High dose intensity protocol 6
2.4 Co-administration of chemotherapy 7
2.5 Replacing cyclophosphamide with L-ASP 8
Chapter 3 Objectives 11
Chapter 4 Material and Methods 12
4.1 Patient collection and evaluation 12
4.2 The 15-week LHOP protocol 13
4.3 Treatment response assessment 14
4.4 Relapse protocol 15
4.5 Historical comparison groups 16
4.6 Statistical analysis 17
Chapter 5 Results 18
5.1 Study population 18
5.2 Comparison of the protocols 20
Chapter 6 Discussion 21
6.7 Limitation 31
Chapter 7 Conclusions 32
Figures 33
Tables 35
REFERENCE 38
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dc.language.isozh_TW-
dc.subject犬隻zh_TW
dc.subject淋巴癌zh_TW
dc.subject化療zh_TW
dc.subject天冬酰胺酶zh_TW
dc.subjectCanineen
dc.subjectL-asparaginaseen
dc.subjectchemotherapyen
dc.subjectlymphomaen
dc.title評估15 週 LHOP化療療程對多中心型淋巴瘤犬隻的療效zh_TW
dc.titleEvaluate the efficacy of a 15-week LHOP chemotherapy protocol including vincristine, L-asparaginase, doxorubicin, and prednisolone on dogs with multicentric lymphomaen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee李繼忠;廖泰慶;劉品辰zh_TW
dc.contributor.oralexamcommitteeJih-Jong Lee;Tai-Ching Liao;Pin-Chen Liuen
dc.subject.keyword犬隻,淋巴癌,化療,天冬酰胺酶,zh_TW
dc.subject.keywordCanine,lymphoma,chemotherapy,L-asparaginase,en
dc.relation.page42-
dc.identifier.doi10.6342/NTU202401649-
dc.rights.note同意授權(全球公開)-
dc.date.accepted2024-07-11-
dc.contributor.author-college生物資源暨農學院-
dc.contributor.author-dept獸醫學系-
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