Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Medicine, Medical College of Georgia, Augusta, Georgia.
Cancer. 2021 Aug 1;127(15):2641-2647. doi: 10.1002/cncr.33539. Epub 2021 Apr 6.
Dasatinib monotherapy has demonstrated modest clinical activity in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP). The outcome of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) has dramatically improved with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with tyrosine kinase inhibitors (TKIs).
The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib.
In the CML-LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML-LBP. The BCR-ABL1 transcript was p210 in 22 patients (96%) and p190 in 1 patient (4%). In the Ph-positive ALL cohort, p210 and p190 transcripts were detected in 13 patients (21%) and 48 patients (77%), respectively. Patients with CML-LBP were less likely to achieve deep molecular remission than patients with Ph-positive ALL: the major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). Survival outcomes were similar for CML-LBP and Ph-positive ALL: the 5-year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML-LBP (5-year OS rate, 88% vs 57%; P = .04). In Ph-positive ALL, the outcome was driven by deeper molecular remission: the 5-year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002).
The outcome of CML-LBP has improved with hyper-CVAD plus dasatinib therapy with survival comparable to that of Ph-positive ALL. Further improvement may be achieved with the use of novel TKIs and targeted agents.
达沙替尼单药治疗慢性髓性白血病淋巴母细胞样期（CML-LBP）具有一定的临床疗效。高剂量环磷酰胺、硫酸长春新碱、盐酸多柔比星和地塞米松（hyper-CVAD）联合酪氨酸激酶抑制剂（TKI）治疗费城染色体（Ph）阳性急性淋巴细胞白血病（ALL）可显著改善预后。
作者回顾了 85 例接受 hyper-CVAD 联合达沙替尼治疗的患者（23 例 CML-LBP 和 62 例新诊断的 Ph 阳性 ALL）。
在 CML-LBP 队列中，19 例患者既往有慢性髓性白血病慢性期（n=17；74%）、加速期（n=1；4%）或髓样母细胞期（n=1；4%）；4 例（17%）为初发 CML-LBP。22 例患者（96%）BCR-ABL1 转录本为 p210，1 例患者（4%）为 p190。Ph 阳性 ALL 队列中，分别有 13 例（21%）和 48 例（77%）患者检测到 p210 和 p190 转录本。CML-LBP 患者获得深度分子缓解的可能性低于 Ph 阳性 ALL 患者：主要分子缓解（MMR）率分别为 70%和 95%（P=0.007），完全分子缓解（CMR）率分别为 55%和 74%（P=0.16）。CML-LBP 和 Ph 阳性 ALL 的生存结局相似：5 年总生存率（OS）率分别为 59%和 48%（P=0.97）。allo-SCT 与 CML-LBP 较好的预后相关（5 年 OS 率分别为 88%和 57%；P=0.04）。在 Ph 阳性 ALL 中，更深的分子缓解是生存的决定因素：CMR 和 MMR 的 5 年 OS 率分别为 63%和 25%（P=0.002）。
hyper-CVAD 联合达沙替尼治疗 CML-LBP 的疗效改善，生存情况与 Ph 阳性 ALL 相似。新型 TKI 和靶向药物的应用可能进一步改善预后。
