TKIs 사용 중 BCR-ABL1 T315I mutation이 확인되면 ponatinib으로 변경하고 allogeneic HCT에 대한 평가를 동시에 시작합니다.
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T315I mutation — In the setting of BCR-ABL1 T315I mutation, we start treatment with ponatinib and simultaneously initiate evaluation for allogeneic HCT. We closely monitor the patient's cytogenetic and molecular status while administering ponatinib and titrate ponatinib to the lowest dose that maintains a cytogenetic response, in an attempt to diminish the incidence of cardiovascular side effects. We proceed with allogeneic HCT if complete cytogenetic remission is not achieved. Options for patients who are ineligible for HCT include treatment with omacetaxine, a chemotherapeutic regimen, or a clinical trial of an investigational agent. |
CML에서 allogeneic HCT를 한 경우 disease phase가 생존의 가장 중요한 prognostic factor입니다. Chronic phase, accelerated phase, blastic phase로 갈수록 생존률은 떨어집니다.
Survival after allogeneic transplant in chronic myelogenous leukemia
This graph shows the probability of survival versus years after allogeneic hematopoietic cell transplantation in patients with chronic myelogenous leukemia (CML) in chronic phase (red), accelerated phase (blue), and blast crisis (green). The difference in survival between patients in chronic phase and blast crisis was statistically significant (p < 0.004).
Allogeneic HCT가 chronic phase로 갈수록 생존률이 높을지라도 TKIs보다 초기 사망률이 높으므로 1차 치료제는 TKIs입니다. Blastic phase, accelerated phase에서 allogeneic HCT 생존률이 낮을지라도 TKIs보다 높으므로 이 단계에서는 allogeneic HCT를 시행합니다.
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Rationale — We recommend a tyrosine kinase inhibitor (TKI) for initial treatment of CP CML rather than allogeneic hematopoietic cell transplantation (HCT) or other medical therapies (eg, interferons, hydroxyurea, busulfan, omacetaxine). This recommendation is based on the more favorable balance of toxicity and long-term disease control with TKIs compared with other approaches. Although allogeneic HCT can achieve long-term disease control and a higher rate of cure than TKIs, it is not recommended as initial therapy for CP CML because of substantially greater toxicity, including early mortality. Other medical treatments are less effective than TKIs for achieving remission and are only appropriate as initial therapy of CP CML in special settings (eg, pregnancy). |
REF. UpToDate 2020.08.16
NCCN 2020 guideline
