Javier Pinilla-Ibarz, MD, PhD
One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. 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. 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). However, the 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), while 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). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.
Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.