A substantial improvement in survival after post-transplant relapse has been achieved in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukaemia, a European study has shown.

Over the last 20 years the two-year overall survival (OS) rate after transplant failure has nearly doubled in this patient population, according to a study published in Clinical Cancer Research.

A retrospective, registry-based study that included 899 adult patients with relapsed Ph+ ALL after allogeneic hematopoietic cell transplantation (HCT) found that long-term survival rates rose from 27.8% in patients who relapsed between 2000 and 2004 to 54.8% in those who relapsed between 2015 and 2019

The study, conducted by the Acute Leukaemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT) also showed that survival increased with the length of time between HCT and relapse.

Lead investigator Professor Ali Bazarbachi of the Bone Marrow Transplant Program, American University of Beirut Medical Center said it was notable that the survival improvement was observed despite a significant increase in patient age at the time of relapse (from 44 to 56 years).

“This makes our findings even more impressive because, typically, longer survival is associated with younger age at the time of relapse,” he said.

The increases in survival were likely due to better supportive care and the greater efficacy of the novel targeted therapies such as newer-generation tyrosine kinase inhibitors, and immunotherapy such as blinatumomab, inotuzumab ozogamicin, and CAR-T cell therapy, the authors suggested.

Increased donor availability and wider use of matched unrelated donors meant that second allogeneic HCT as salvage therapy was an option for more patients, they added.

A second allogenic HCT within two years after relapse was performed in 14% of patients, resulting in a two-year OS from the date of the second transplant of 35.9%, with a progressive decrease in the two-year relapse incidence from the date of the second transplant (74% in the 2000-2004 period and 33% in the 2015-2018 period.)

“In the subset of ALL patients carrying the Philadelphia chromosome, post-transplant relapse occurs in up to 30% of the cases, and in earlier studies, long-term survival was dismal,” said Professor Bazarbachi.

“Our study represents the largest analysis to date assessing the outcomes and characteristics of patients with relapsed Ph+ ALL after allogeneic HCT, and our findings proved that the survival of these patients has significantly improved over time … These large-scale real-world data can serve as a benchmark for future studies in this setting,” he said.