Lymphocyte Infusion Effective Following CML Relapse After HSCT

Lymphocyte infusions are extremely effective therapy in patients with chronic myeloid leukemia (CML) who relapse after allogeneic hematopoietic stem cell transplantation (HSCT), and the timing of the infusion is relatively unimportant, according to a new study.

Patients with CML who relapse following HSCT are generally treated with either donor lymphocyte infusion (DLI) or with tyrosine kinase inhibitors (TKIs), or with both. “The best strategy, with respect to using either or both of DLI and TKI, and the timing of these in relation to the relapse is not yet established,” wrote authors led by Yves Chalandon, MD, of University Hospital Geneva in Switzerland. The new study included 155 CML patients who relapsed following stem cell transplantation and who subsequently did receive lymphocytes.

The patients received lymphocytes either during molecular relapse (85 patients) or upon progression to more advanced disease (70 patients); the median interval between relapse to lymphocyte infusion was 210 days, and the median follow-up after the infusion was 46 months.

The 5-year overall survival (OS) rate was 76%; the rate was 89% among those with sibling donors, and 63% with unrelated donors, a significant difference (P = .003). Five-year OS was 69% when lymphocyte infusion took place within 6 months of molecular relapse detection, compared with 81% when given later (P = .061). Also, OS was 81% if infusion occurred at molecular relapse vs 71% with more advanced disease (P = .26).

A multivariate analysis was also conducted, and confirmed the worse survival if the donor was unrelated, with a hazard ratio (HR) of 2.54 (95% CI, 1.15-5.53; P = .021). It also showed that some aspects of infusion timing do matter, with a significant improvement with lymphocyte infusion beyond 6 months from molecular relapse, with an HR of 0.4 (95% CI, 0.19-0.84; P = .018).

The study is limited by its retrospective nature, but the authors wrote that it confirms the ability of DLI to rescue many CML patients who relapse following HSCT. They noted the somewhat odd finding that waiting longer for DLI seemed to have a protective effect. “This message is rather counterintuitive as one would normally think that the sooner the treatment for relapse is delivered, the better,” they wrote. “This finding may be related to the particular natural course and biology of the disease as CML is usually a slow evolving disease and patients in cytogenetic or hematological relapses will still have some months or years before advancing to blast phase and death.” The data from this study should be used as a benchmark in future studies comparing DLI with TKI therapy, they concluded.

Study Details

The study population included patients transplanted between 1986 and 2003 at 28 centers, and none were treated with imatinib prior to transplant. The median time from HSCT to molecular relapse was 239 days; 64 patients (41%) received DLI within 6 months of the detection of relapse. Thirty-one of the 155 patients died, including 15 from relapse, 14 from DLI-related complications, and 2 from non-DLI or CML causes.