接受 Hyper-CVAD 和达沙替尼治疗的慢性髓性白血病伴淋巴母细胞样变期和费城染色体阳性急性淋巴细胞白血病患者的结局。

Outcome of patients with chronic myeloid leukemia in lymphoid blastic phase and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with hyper-CVAD and dasatinib.

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Department of Medicine, Medical College of Georgia, Augusta, Georgia.

出版信息

Cancer. 2021 Aug 1;127(15):2641-2647. doi: 10.1002/cncr.33539. Epub 2021 Apr 6.

DOI:10.1002/cncr.33539

PMID:33823073

Abstract

BACKGROUND

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).

METHODS

The authors reviewed 85 patients (23 with CML-LBP and 62 with newly diagnosed Ph-positive ALL) who received hyper-CVAD plus dasatinib.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景

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。

方法

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）。

结果

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）。