Davidson Marta B, Kennedy James A, Capo-Chichi Jose-Mario, Shi Yuliang, Xu Wei, Cheung Verna, Arruda Andrea, Bankar Aniket, Richard-Carpentier Guillaume, Chan Steven, Maze Dawn, Minden Mark D, Schimmer Aaron D, Schuh Andre C, Sibai Hassan, Yee Karen, Tierens Anne, Viswabandya Auro, Gupta Vikas
Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Medical Oncology and Hematology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Blood Adv. 2024 Mar 12;8(5):1281-1294. doi: 10.1182/bloodadvances.2023011735.
Transformation of BCR::ABL1-negative myeloproliferative neoplasms (MPN) to an accelerated or blast phase is associated with poor outcomes. The efficacy of acute myeloid leukemia (AML)-type intensive and nonintensive hypomethylating agent-based regimens is not well studied. We therefore performed a retrospective analysis of patients with MPN-AP/BP (N = 138) treated with intensive (N = 81) and nonintensive (N = 57) blast-reduction strategies. We used clinically relatable response criteria developed at the Princess Margaret Cancer Centre. The overall best response, comprising complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and reversion to chronic phase MPN (cMPN), in the intensive and nonintensive groups was 77% (62 of 81) and 39% (21 of 54), respectively. Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23 of 31]) or FLAG-IDA/NOVE-HiDAC (78% [39 of 50], P = .78). However, patients receiving daunorubicin + ara-C more often required second inductions (29% [9 of 31] vs 4% [2 of 50], P = .002). Most responses in the entire cohort were reversions to cMPN (55 of 83 [66%]). CR and CRi comprised 30% (25 of 83) and 4% (3 of 83) of responses, respectively. Mutations in TP53 (overall response [OR] 8.2 [95% confidence interval [CI] 2.01, 37.1], P = .004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], P = .03) were associated with inferior treatment response for intensively treated patients, and poorer performance status (Eastern Cooperative Oncology Group) was associated with inferior treatment response in both intensively (OR 10.4 [95% CI 2.0, 78.5], P = .009) and nonintensively treated groups (OR 12 [95% CI 2.04, 230.3], P = .02). In patients with paired samples before and after therapy (N = 26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.
:ABL1阴性骨髓增殖性肿瘤（MPN）转变为加速期或急变期与预后不良相关。基于急性髓系白血病（AML）类型的强化和非强化低甲基化药物方案的疗效尚未得到充分研究。因此，我们对接受强化（N = 81）和非强化（N = 57）降低原始细胞策略治疗的MPN-AP/BP患者（N = 138）进行了回顾性分析。我们使用了玛格丽特公主癌症中心制定的临床相关反应标准。强化组和非强化组的总体最佳反应，包括完全缓解（CR）、血液学未完全恢复的完全缓解（CRi）和恢复至慢性期MPN（cMPN），分别为77%（81例中的62例）和39%（54例中的21例）。在接受柔红霉素联合阿糖胞苷（柔红霉素+阿糖胞苷）诱导治疗（74%[31例中的23例]）或FLAG-IDA/NOVE-HiDAC诱导治疗（78%[50例中的39例]，P = 0.78）的患者中观察到相似的总体最佳反应率。然而，接受柔红霉素+阿糖胞苷治疗的患者更常需要第二次诱导治疗（29%[31例中的9例]对4%[50例中的2例]，P = 0.002）。整个队列中的大多数反应是恢复至cMPN（83例中的55例[66%]）。CR和CRi分别占反应的30%（83例中的25例）和4%（83例中的3例）。TP53突变（总体反应[OR]8.2[95%置信区间[CI]2.01, 37.1]，P = 0.004）和RAS通路突变（OR 5.1[95%CI 1.2, 23.7]，P = 0.03）与强化治疗患者的治疗反应较差相关，而较差的体能状态（东部肿瘤协作组）与强化治疗组（OR 10.4[95%CI 2.0, 78.5]，P = 0.009）和非强化治疗组（OR 12[95%CI 2.04, 230.3]，P = 0.02）的治疗反应较差相关。在治疗前后有配对样本的患者（N = 26）中，无论对降低原始细胞治疗的反应如何，均存在显著的残留突变负担。
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