2-Year OS Improves Over 20 Years in Relapsed Ph+ ALL Post Allogeneic Transplant

Ali Bazarbachi, MD, PhD

The 2-year overall survival (OS) rate almost doubled between 2000 and 2004 and 2015 and 2019 in patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) who had relapsed after allogeneic hematopoietic cell transplant, indicating improvements in patient care overall, according to findings from a study published in Clinical Cancer Research.

At a median follow-up of 56 months for surviving patients, the 2-year OS rate after relapse was 41.5% (95% CI, 38%-44.9%) among the entire cohort. Notably, the 2-year OS rate after relapse increased from 27.8% for patients who relapsed between 2000 and 2004 to 31.7% for 2005 and 2009, 44.5% for 2010 and 2014, and 54.8% for 2015 and 2019 (P = .001).

“We observed a major progressive improvement in OS from posttransplant relapse for patients with Ph-positive 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,” lead study author Ali Bazarbachi, MD, PhD, associate dean and professor in the Bone Marrow Transplant Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon, and coauthors wrote in the study publication.

Relapse remains the top cause of transplant failure in patients with Ph-positive ALL following allogeneic transplant. In other hematologic malignancies, OS has improved in patients who relapsed after transplant.

To better understand trends in OS in patients with Ph-positive ALL posttransplant, investigators collected the outcomes from European Society for Blood and Marrow Transplantation participating centers of 899 adult patients with Ph-positive ALL who relapsed between 2000 and 2019 after allogeneic transplant. All transplants had been done in first complete remission.

In the retrospective, registry-based, multicenter analysis, 116 patients had relapsed between 2000 and 2004, 225 between 2005 and 2009, 294 between 2010 and 2014, and 264 between 2015 and 2019.

The probability of OS after relapse served as the primary end point of the study, with secondary end points of death within 2 years post relapse, the cumulative incidence of second allogeneic transplant after relapse, and OS after second allogeneic transplant.

Patient and transplant characteristics were comparable over the 4 time periods apart from a gradual increase in the use of matched unrelated donors (P = .0002), peripheral blood stem cells (P < .0001), reduced intensity conditioning (P = .004), and in vivo T-cell depletion (P < .0001) and a gradual decrease in total body irradiation (P = .0002).

The median age at transplant and relapse was 44 and 45.4 years, respectively.

Additional results showed that the cause of death decreased from 72.2% for patients who relapsed between 2000 and 2004 to 50% for 2015 and 2019, whereas infections increased from 8.2% to 30.6% for the same periods.

Furthermore, within 2 years of relapse, 13.9% of patients underwent another allogeneic transplant, resulting in a 2-year OS rate of 35.9% (95% CI, 26.5%-45.4%). The cumulative incidence of a second allogeneic transplant within 2 years after relapse was 22%, 13%, 10%, and 16% for the four time periods (P = .009).

Notably, the rate of 2-year relapse from second transplant decreased from 74% between 2000 and 2004 to 54% for 2005 and 2009, 46% for 2010 and 2014, and 33% for 2015 and 2018 (P = .03).

In multivariate analysis, OS from relapse was positively influenced by a longer time from transplant to relapse (P = .0006) and the year of relapse for patients relapsing between 2005 and 2009 (HR 0.71; P < .033), 2010 and 2014 (HR, 0.51; P < .0001), and 2015 and 2019 (HR, 0.37; P < .0001) and was negatively influenced by patient age at relapse (P = .034).

“In summary, this study represents the largest analysis to date assessing trends over time and predictive factors for outcome of relapsed Ph-positive ALL after allogeneic transplant. These large-scale real-world data can serve as a benchmark for future studies in this setting,” concluded the authors.

Reference

1. Bazarbachi A, Labopin M, Aljurf M, et al. 20-year steady increase in survival of adult patients with relapsed Philadelphia-positive acute lymphoblastic leukemia post allogeneic hematopoietic cell transplantation. Clin Cancer Res. Published online January 12, 2022. doi:10.1158/1078-0432.CCR-21-2675