Early BCR-ABL transcript test for better treatment in CML patients !!!

Quantitative BCR-ABL transcript testing in blood is an effective method for monitoring disease response to the tyrosine kinase inhibitors imatinib (Gleevec®), dasatinib (Sprycel®), and nilotinib (Tasigna®). BCR-ABL transcript levels generally fall once a patient has achieved complete cytogenetic remission. Test results from blood correlate well with results from bone marrow, and blood has the distinct advantage of being monitored without the need for repeated bone marrow biopsy. BCR-ABL transcript levels assess response to therapy and detect early relapse. For individuals who display apparent treatment resistance, alternative treatments are available.3 Major molecular response (MMR) is achieved when a 3-log reduction or greater in BCR-ABL chimeric mRNA or BCR-ABL:ABL ratio of =0.1% (International Scale) is achieved.1 Major molecular response (MMR) and complete cytogenetic response (CCyR) have been associated with better outcomes. It has been shown that failure to achieve at least a 2-log reduction in BCR-ABL m RNA at the time of CCyR or 3-log reduction (MMR) anytime afterward predicts a negative impact on duration of CCyR and progression-free survival.1,7,8 Molecular monitoring for CML patients is available by measuring RT-PCR transcript levels. ABL tyrosine kinase domain point mutation analysis may provide additional information for those patients who are suspected to have resistance to TKI therapy. These patients may have had an inadequate initial response, loss of response, or an increase in BCR-ABL transcript levels. BCR-ABL quantitative RT-PCR is the routine monitoring method for response to TKI therapy in CML.8  Genetic testing (BCR-ABL quantitative RT-PCR) is offered to patients whose employers or health plans have enrolled their members in the Medco personalized medicine program. BCR-ABL transcript levels, as well as patient adherence rates, are then provided. Treatment recommendations that take into account both patient adherence to therapy and BCR-ABL expression may prevent unnecessary changes to therapy. The program is offered at no cost to eligible members and their physicians. If you are not sure whether a patient is eligible for Medco's personalized medicine program for Gleevec, Sprycel and Tasigna, please contact a Medco representative at 1 877 285-0761, 9:00 a.m. and 5:30 p.m. eastern time, Monday through Friday. There is significant variability in results from individual laboratories due to different instruments, chemistry of assays, different protocols for RT-PCR and sample handling and storage. Until an international standard is utilized by laboratories, it is not possible to compare results from different laboratories. For this reason, it is important not to change laboratories during the course of monitoring BCR-ABL.10  Once testing is ordered, 3 to 5 mL whole blood (EDTA containing tube) is collected from the patient. BCR-ABL quantitative polymerase chain reaction (RT-PCR) testing is performed by Medco's lab partner, and results and therapeutic considerations are shared back with the physician who ordered the test.

白血病用藥新指引 助縮短試藥期   (2012年08月21日)俗稱血癌的白血病為本港十大癌症殺手之一，其中慢性骨髓性白血病(Chronic Myeloid Leukemia, CML)佔總白血病患者約15%，每年有至少40至50宗新症。以往患者接受標靶藥物治療時，需要在十八個月內，檢測治療反應，若未如理想便轉藥，但外國的研究證實，只須三個月便可確認患者的治療反應，讓患者及早轉藥，更有效及盡快控制病情。 現時全港約有400至500名CML患者，患者多為50至60歲人士。患者一般會先服用第一代標靶治療藥物「伊馬替尼」，並於治療間十八個月內接受檢測，量度體內的「變異基因表達水平」，即「癌變水平」。十八個月後，若水平未能降至0.1%，醫生才會為患者轉服第二代標靶治療藥物「尼洛替尼」。然而，當中三成至四成人或會對傳統藥物呈抗藥性或因基因突變，增加病情惡化風險。

水平愈低控制愈理想 香港大學內科學系教授鄺沃林表示，「變異基因表達水平」反映患者體內癌細胞數量，故定期量度表達水平對監測病情十分重要。若表達水平愈低，即病情控制愈理想，惡化或復發機會亦相對較低。 英國最新發表的研究證實，患者接受治療三個月後，便能知道治療反應。若患者變異基因表達水平降至治療前的10%，預期8年後的整體存活率可高於九成，較無法達標者高出四成。至於未達標的患者，可考慮轉用第二代藥物，比以往需待十八個月才轉藥，新指引的時間大為縮短。

冀本港醫生採用新指引 鄺沃林希望本港醫生能採用新指引，協助療程首三個月未達標的CML患者轉用第二代藥物，以助控制病情。而第二代藥物「尼洛替尼」相對傳統藥物「伊馬替尼」藥效多30至100倍，產生的副作用如頭痛、噁心等亦較少，同時能減低病情惡化達6倍。 現年28歲的郭先生，約6年前發現自己漸漸消瘦、容易疲倦。喜愛做運動的他，在一次他與友人游泳時發現腹部異常脹大，經檢查證實患上慢性骨髓性白血病。他服用傳統藥物4至5年，變異基因表達水平持續處於0.2%至0.4%，未能降至0.1%的理想水平。後來，郭先生經建議轉服新藥，至今已有一年多，水平成功降低至0.12%。