1、淋巴瘤教案,高雄榮民總醫院 藥劑部 Speaker ：方柔壹 藥師 100.11.26,1,Outline,教案學習目標教案設計的注意事項 在設計教案之前 疾病治療-建議參考資料教案設計與問題討論 (SOAP),2,教案學習目標,了解淋巴瘤的藥物治療 了解藥物相關問題：適當的藥物治療、治療中的注意事項及藥物不良反應 治療目標的達成：設立治療目標、確保病患依順性學習以SOAP格式建立完整的合理用藥評估 了解病患案例報告(case presentation)之結構及順序 說明SOAP之格式組成及擷取治療準則所需資訊,3,教案設計的注意事項,在設計教案之前 依對象設計教案難易 Burkitts Ly
2、mphoma的表現、診斷 確定教案的問題發生在疾病初期還是治療中 疾病治療-建議參考資料 臨床指引 (clinical practical guideline)NCCN practice guidelineAmerican Society of Clinical Oncology /ASCO - Journal of clinical oncologyEuropean Society for Medical Oncology / ESMO Annals of Oncology,4,教案設計與問題討論 (SOAP),什麼是淋巴瘤 ?,5,Textbook & Uptodate,6,Normal
3、lymph nodes are usually less than 1 cm in diameter and tend to be larger in adolescence than later in life. Lymph nodes are often palpable in the inguinal region in healthy people.,7,Aggressive lymphomas commonly present acutely or subacutely with a rapidly growing mass, systemic B symptoms, and/or
4、elevated levels of serum LDH and uric acid,B symptoms Fever (BT 38) Night sweats Weight loss (loss 10% weight within 6 months),These cancers arise from cells of the immune system at different stages of differentiation, resulting in a wide range of morphologic, immunologic, and clinical findings.Lymp
5、homasumors of the immune system.,Malignancies of lymphoid cells,8,HARRISONS_Hematology and Oncology textbook, 17th ed,The WHO classification takes into account morphologic, clinical, immunologic, and genetic formation and attempts to divide non-Hodgkins lymphomas and other lymphoid malignancies into
6、 clinical/pathologic entities that have clinical and therapeutic relevance.,9,HARRISONS_Hematology and Oncology textbook, 17th ed,Relative frequency of lymphoid malignancies,10,HARRISONS_Hematology and Oncology textbook, 17th ed,97年度 Non-Hodgkins Lymphoma佔整年度癌症死亡率 1941 38913 5,衛生署統計資料_臺灣地區惡性淋巴瘤申報發生人
7、數,11,衛生署健康局癌症組,A number of environmental factors have been implicated in the occurrence of non-Hodgkins lymphoma, including infectious agents, chemical exposures, and medical treatments. Several studies have demonstrated an association between exposure to agricultural chemicals and an increaseed inc
8、idence in non-Hodgkins lymphoma.,12,HARRISONS_Hematology and Oncology textbook, 17th ed,Burkitts Lymphoma morphology and immunophenotyping,The neoplastic cells are homogenous, small to medium-sized B cells with frequent mitotic figures, a morphologic correlate of high growth fraction. Reactive macro
9、phages are scattered through the tumor, and their pale cytoplasm in a background of blue-staining tumor cells give the tumor a so-called starry sky appearance.2. The classical immunophenotypeof BL is IgM+/CD10+/CD20+/BCL2-/BCL6+ and TdT (-), with the Ki-67proliferation index 95%.The chromosomal tran
10、slocation t(8;14)(q24;q32) or one of its variants t(8;22) or t(2;8).,13,HARRISONS_Hematology and Oncology textbook, 17th ed,Three distinct clinical forms of Burkitts lymphoma are recognized; endemic, sporadic, and immunodeficiency associated.Endemic and sporadic Burkitts lymphomas occur frequently i
11、n children in Africa, and the sporadic form in Western countries. Immunodeficiency-associated Burkitts lymphoma is seen in patients with HIV infection.BL present with peripheral lymphadenopathy or an intraabdominal mass. The disease is rapidly progressive and has a propensity to metastasize to the C
12、NS. Initial evaluation should always include an examination of cerebral spinal fluid to rule out metastasis.,Characteristics of Burkitts Lymphoma,14,HARRISONS_Hematology and Oncology textbook, 17th ed,案例討論 (Non-Hodgkins Lymphoma)Burkitts lymphoma,15,Case Presentation,16,Case Presentation,17,Case Pre
13、sentation,18,Case Presentation,19,20,Case Presentation,Case Presentation,21,Case Presentation,22,Case Presentation,DiagnosisBurkitts lymphoma,23,24,25,26,27,28,29,Treatment for Burkitts Lymphoma,30,Those patients with all of the following features were regarded as low risk : (i) normal LDH level; (i
14、i) WHO performance status of 0 or 1; (iii) Ann Arbor stage III; and (iv) no tumor mass 10cm. All remaining patients were considered high risk.,LDH 191 U/LPS 1Stage IaThe mass was about 44 cm,Low risk Burkitts Lymphoma,31,Treatment for Burkitts Lymphoma,32,Original CODOX-M regimen- Cyclophosphamide,
15、vincristine, doxorubicin, high-dose methotrexate,Epirubicin 60mg/m2,33,CNS prophylaxis Intrathecal Ara-C & MTX,Modified CODOX-M Regimen,34,High dose MTX : decreased from 6,720 mg/m2 to 3,000 mg/m2, reduce toxicity while maintaining adequate CNS penetrationEndoxan was changed from 800 mg/m2 day 1 fol
16、lowed by 200 mg/m2 days 25 to800 mg/m2 days 1 and 2 to reduce myelosuppressionIT Ara-C was reduced from 70 mg to 50 mg to reduce the incidence of neurotoxicity,Modified Magrath Regimens for Adults with Burkitts and Burkitt-Like Lymphomas: Preserved Efficacy with Decreased Toxicity,There were a total
17、 of 16 relapses (20%). Fewer relapses were observed among rituximab-treated patients compared with patients treated with chemotherapy alone (3 vs. 13, P=0.01).,40 pt received rituximab + C/T(R-CODOX-M/R-IVAC) VS. 40 pt treated with C/T alone.,36,Renal functionGFR 1050 mL/min- 50% of the usual dose g
18、iven at the normal interval GFR 50 mL/min No adjustmentLiver functionBilirubin is 180 IU -75% of the doseBilirubin 5.0 mg/dL omitted,Micromedex,Methotrexate dosage adjustment,37,High dose Methotrexate therapy,patient should be given leucovorin to prevent myelosuppression toxicity.Leucovorin commence
19、d 24 h after starting MTX infusion and continued until the serum MTX level 5 108 M,Alkalinization of the urine in patients receiving high-dose methotrexate therapy has also been shown to be effective in preventing nephrotoxicity and attentuating the myelosuppression.,Methotrexate related medical pro
20、blem,Complication _ Tumor lysis syndrome (TLS),It typically occurs in patients with lymphoproliferative malignancies, most commonly observed following chemotherapy for high-grade lymphoproliferative malignancies such as acute lymphocytic leukemia and Burkitts lymphoma, who are exposed to chemotherap
21、y, radiation, or corticosteroids, but can occur spontaneously in the absence of treatment.Release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulation. Renal failure impairmentCatabolism of the nucleic acids to uric acid leads to hyperuricemiaHyperphosphatemia wi
22、th calcium phosphate deposition in the renal tubules,Complication _ Tumor lysis syndrome (TLS),Certain intrinsic tumor-related high risk factors High tumor cell proliferation rate Chemosensitivity of the malignancy Large tumor burden, as manifested by -bulky 10 cm -WBC 50,000 /ul-LDH 2 ULN,40,41,Liv
23、er impairment/ Toxicity,Response criteria for lymphoma,42,(complete remission),(partial remission),43,44,Rituximab 需經事前審查核准後使用 限用於 復發或對化學療效有抗性之低惡度B細胞非何杰金氏淋巴瘤。 併用CHOP或其他化學療法，用於CD20抗原陽性之B瀰漫性大細胞非何杰金氏淋巴瘤之病患。 併用CVP化學療法，用於未經治療之和緩性（組織型態為濾泡型）B細胞非何杰金氏淋巴瘤的病人。 用於做為濾泡性淋巴瘤患者對誘導療法產生反應之後的維持治療用藥。限用八劑，每三個月使用一劑，最多不超過
24、二年。,In the current issue of Haematologica, as well as in other series, the outcome of these patients is dismal irrespective of standard R-CHOP or intensified treatment including bone marrow transplantation. 17 While in elderly patients, who actually form the majority of this group, this may be suffi
25、cient grounds to refrain from aggressive treatment, this policy may not be acceptable for younger and fit patients. In these patients, treatment with BL regimens may therefore be preferred over standard R-CHOP, which will certainly not be sufficient to control the disease.,Haematologica, 2009; 94(7)
26、, p894,Lymphomas fall into one of two major categories: Hodgkins lymphoma (HL, previously called Hodgkins disease) and all other lymphomas (non-Hodgkins lymphomas or NHLs).These two types occur in the same places, may be associated with the same symptoms, and often have similar appearance on physica
27、l examination. However, they are readily distinguishable via microscopic examination. Hodgkins disease develops from a specific abnormal B lymphocyte lineage. NHL may derive from either abnormal B or T cells and are distinguished by unique genetic markers.There are five subtypes of Hodgkins disease
28、and about 30 subtypes of non-Hodgkins lymphoma.Because there are so many different subtypes of lymphoma, the classification of lymphomas is complicated (it includes both the microscopic appearance as well as genetic and molecular markers). Many of the NHL subtypes look similar, but they are functionally quite different and respond to different therapies with different probabilities of cure. HL subtypes are microscopically distinct, and typing is based upon the microscopic differences as well as extent of disease.,
