A retrospective, registry-based multicenter study by Bazarbachi et al published in Clinical Cancer Research evaluated clinical outcomes in patients with relapsed Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic cell transplantation over a 20-year period. The investigators found that 2-year overall survival after relapse nearly doubled by the end of that time period—to 55%. This real-world outcome may serve as a benchmark to guide the development of new therapeutic approaches in future clinical trials, according to the study authors.

Although allogeneic hematopoietic cell transplantation is potentially curative treatment for adult patients with Ph+ ALL, historically, the relapse rate posttransplant was significant, and long-term overall survival remained low. However, advances in posttransplant pharmacologic interventions—including newer-generation tyrosine kinase inhibitor–based maintenance therapy; monoclonal antibodies, such as blinatumomab and inotuzumab ozogamicin; and chimeric antigen receptor T-cell therapy—aimed at reducing the risk of relapse in these patients are now being widely used in this setting. In addition, the increased availability of alternative donors and a progressive increase in the use of matched unrelated donors is facilitating second allogeneic hematopoietic cell transplantation as salvage therapy.

Study Methodology

The researchers compared patient outcomes data provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. The study included 899 adult patients with Ph+ ALL who relapsed between 2000 and 2019 following an allogeneic hematopoietic cell transplant performed in first complete remission. Median follow-up was 56 months.

Results

The researchers found that, overall, 116 patients relapsed between 2000 and 2004; 225 between 2005 and 2009; 294 between 2010 and 2014; and 264 between 2015 and 2019. Patient and transplant characteristics were similar over the four time periods, except for a progressive increase in unrelated donors, peripheral blood stem cells, reduced-intensity conditioning, and in vivo T-cell depletion; and a progressive decrease in use of total-body irradiation.  

The 2-year overall survival after relapse increased from 27.8% for patients who relapsed between 2000 and 2004 to 54.8% for patients who relapsed between 2015 and 2019 (P = .001). A second allogeneic hematopoietic cell transplantation within 2 years after relapse was performed in 13.9% of the patients, resulting in a 2-year overall survival of 35.9%.

In a multivariate analysis, overall survival from relapse was positively affected by a longer time from transplant to relapse and the year of relapse. Notably, 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,” commented lead study author Ali Baxarbachi, MD, PhD, Professor of Medicine, Associate Dean for Basic Research, and Director of the Bone Marrow Transplantation Program at the American University of Beirut. “This effect is likely due to the greater efficacy of the novel targeted therapies.”

Translational Significance

“In the subset of ALL patients carrying the Philadelphia chromosome, posttransplant relapse occurs in up to 30% of the cases, and in earlier studies, long-term survival was dismal,” said Dr. Baxarbachi. “However, several new therapeutic strategies have been recently approved for these patients; therefore, it was important to study and compare the clinical outcomes between different time periods in the past 20 years.”

“We observed a major progressive improvement in overall survival from posttransplant relapse for patients with Ph+ ALL over the years, likely multifactorial, including transplant-related factors, posttransplant salvage, and improvement in supportive care. These large-scale real-world data can serve as a benchmark for future studies in this setting,” concluded the study authors.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.