Survival Rate Increased Over 2 Decades for Relapsed Ph+ Acute Lymphoblastic Leukemia After Hematopoietic Cell Transplantation

From the period of 2000 and 2004 to 2015 and 2019, 2-year overall survival (OS) has almost doubled for patients with Philadelphia chromosome–positive (Ph-positive) acute lymphoblastic leukemia (ALL) who relapsed following allogeneic hematopoietic stem cell transplantation (AHCT), according to results from a study published in Clinical Cancer Research.¹

Investigators noted that 2-year OS increased from 27.8% among those with Ph-positive ALL who relapsed in 2000 to 2004 to 54.8% for those who relapsed between 2015 to 2019 (P = .001). Moreover, 13.9% of patients underwent a second AHCT within 2 years after relapse, which resulted in a 2-year OS from the date of second relapse of 35.9%. Investigators also observed a progressive decrease in incidence of 2-year relapse from 74% between 2000 to 2004 to 33% from 2015 to 2018.

“In the subset of ALL patients carrying the Philadelphia chromosome, post-transplant relapse occurs in up to 30 percent of the cases, and in earlier studies, long-term survival was dismal,” corresponding author Ali Bazarbachi, MD, PhD, professor of medicine, associate dean for basic research, and director of the Bone Marrow Transplantation Program at the American University of Beirut, said in a press release.² “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.”

Ph+ ALL accounts for approximately 30% of all adult ALL cases, which is associated with a worse prognosis for patients. Although AHCT is seen as a potentially curative option for patients with ALL, relapse after transplant is common and remains the main reason for failure of AHCT.

The retrospective, registry-based, multicenter study included 899 adult patients with Ph+ ALL who relapsed after AHCT from 2000 to 2019 following ASCT in first complete remission. The median follow up for living patients was 56 months. A total of 116 patients relapsed from 2000 to 2004, 225 relapsed in 2005 to 2009, 294 relapsed in 2010 to 2014, and 264 relapsed from 2015 to 2019. Patient characteristics were mostly similar across all 4 time points with the exception of a progressive increase in unrelated donors, peripheral blood stem cells, a reduction in intensity conditioning, in-vivo T-cell depletion, and a progressive decrease in total body irradiation.

Additionally, OS from relapse was positively impacted by a longer time from transplant to relapse and the year of relapse, according to findings from a multivariate analysis.

Despite a significant increase in age among patients at the time of relapse from 44 years to 56 years, an improvement in survival was observed. Barzarbachi explained that longer survival is typically observed in patients who relapse at a younger age, making the results all the more impressive.

The research team emphasized that a lack of information on the post-transplant relapse treatment and how it impacts survival data is a limitation of this study.

“Our study represents the largest analysis to date assessing the outcomes and characteristics of patients with relapsed Ph+ ALL after AHCT, 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,” Bazarbachi concluded.

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 Can Res. Published online January 12, 2022. doi:10.1158/1078-0432.CCR-21-2675
2. Survival rate of adult patients With relapsed acute lymphoblastic leukemia after hematopoietic cell transplantation has steadily increased over the past two decades. News release. American Association for Cancer Research. January 12, 2022. Accessed January 12, 2022. https://tinyurl.com/vwnt22b8