- 學位論文
異體造血幹細胞移植之前置化療強度對於骨髓纖維化病人之影響：系統性回顧、統合分析與臨床試驗計畫書
Conditioning intensity of allogeneic hematopoietic stem cell transplantation in myelofibrosis: a systematic review and meta-analysis, with a proposed protocol
摘要
背景 血液學的治療日新月異，而近年來即使有了新的治療，包括JAK-STAT信號傳送途徑抑制劑以及其他免疫治療，異體造血幹細胞移植仍被視為骨髓纖維化病人唯一的治癒性治療。在此同時，移植前的前置性化學治療所帶來的毒性一直是醫師與病人共同非常在意的；而移植後幹細胞植入失敗和疾病的復發，也對病人的長期存活有很深的影響。當今對於骨髓纖維化病患接受移植前的前置化療強度並沒有共識，過去也未曾有隨機對照的臨床試驗針對不同強度的前置性化學治療對於移植後的治療成果做出比較。本研究的目的在於比較骨髓纖維化病人在移植前接受清髓性化學治療或者減低強度化學治療，對於移植預後的影響。 方法 作者進行系統性回顧及統合分析，搜尋發表在PubMed、EMBASE和Cochrane Library的文獻。文獻納入條件為經學者評審、有10位以上病人、同一文獻中包含分別接受清髓性治療和減低強度治療的病人。至西元2019年12月1日，共有387 篇文獻被初步審閱，最後有10篇文章納入此研究。總計有2776位病人， 其中1048位接受了清髓性治療，1728位接受了減低強度的前置化學治療。 結果 清髓性治療相對於減低強度治療，各滿足點的勝算比分別如下：三年整體存活率：1.48（百分之95信賴區間〔95% confidence interval，CI〕：0.71-3.08）；五年整體存活率：0.88（95% CI：0.35-2.19）；三年疾病無惡化存活率：0.81（95% CI：0.42-1.59）；幹細胞植入失敗率：0.66（95% CI：0.51-0.86）；非復發死亡率：0.92（95% CI：0.48-1.77）；疾病復發率：0.56（95% CI：0.27-1.17）；急性排斥累積發生率：1.39（95% CI：0.45-4.30）；慢性排斥累積發生率：1.30（95% CI：0.40-4.19）。 結論 骨髓纖維化病人在造血幹細胞移植前接受清髓性或是減低強度治療，在三年整體存活率、五年整體存活率、三年疾病無惡化存活率、非復發死亡率、疾病復發率以及急、慢性排斥累積發生率方面，並無顯著差異，而接受清髓性前置化學治療的病人，有顯著較低的幹細胞植入失敗率。以前瞻性隨機對照試驗比較此二種治療的結果，雖然執行上不易，仍然可以給我們更多較少偏差的實證證據。
並列摘要
Background Despite the advent of novel therapies, including JAK inhibitors and immunomodulatory agents, allogeneic hematopoietic stem cell transplant (Allo-HSCT) is viewed as the ultimate cure for myelofibrosis (MF). However, treatment toxicities of conditioning regimens are major concerns. Meanwhile, graft failure and relapse after the post-transplant course pose challenges against long-term survival. Currently, there’s neither firm consensus on the conditioning intensity in MF patients nor randomized controlled trials investigating the impact of dose intensity on the post-transplant outcome. This study aims to compare the outcomes of MF patients receiving either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) for Allo-HSCT. Patients and Methods We performed a systematic review and meta-analysis of the published literature extracted from PubMed, EMBASE, and the Cochrane Library. We restricted inclusion criteria to peer-reviewed studies that include both MAC and RIC regimes and more than 10 patients. As of Dec 1st, 2019, 387 potentially relevant studies were identified, but only 10 (2776 patients) met our criteria after evaluation. In total, 1048 patients received MAC regimens while 1728 patients received RIC regimens. Results The odds ratios of MAC/RIC of each endpoint are as following: overall survival (OS) at 3 years: 1.48 (95% confidence interval, CI: 0.71-3.08); OS at 5 years: 0.88 (95% CI: 0.35-2.19); progression-free survival (PFS) at 3 years: 0.81 (95% CI: 0.42-1.59); graft failure: 0.66 (95% CI: 0.51-0.86); non-relapse mortality (NRM): 0.92 (95% CI: 0.48-1.77); relapse incidence: 0.56 (95% CI: 0.27-1.17); and cumulative incidence of acute graft-versus-host disease (GVHD): 1.39 (95% CI: 0.45-4.30) and chronic GVHD: 1.30 (95% CI: 0.40-4.19). Conclusions There is no significant difference between MAC and RIC groups in regard to OS at 3 years and 5 years, PFS at 3 years, NRM, relapse incidence, and cumulative incidence of acute and chronic GVHD, whereas patients in the MAC group had lower graft failure rate. Prospective and randomized controlled trials are warranted to further investigate and compare outcomes of patients receiving different intensities of conditioning therapy, although it is challenging to initiate these trials.