Certain Leukemia Patients Living Longer After Relapse Following Stem Cell Transplant

New interventions and therapies lead to a near doubling of survival of patients with acute lymphoblastic leukemia following relapse after transplants.

The formerly dismal outlook for certain patients with acute lymphoblastic leukemia (ALL) who relapse after stem cell transplantation has brightened considerably over the last 20 years, thanks to new medications and improved therapeutic strategies, according to a study published in the AACR journal Clinical Cancer Research.

The two-year overall survival (OS) increased from 27.8 percent in patients who relapsed between 2000 and 2004 to 54.8 percent in those who relapsed between 2015 and 2019, according to the study. Other indicators also improved.

The study focused on patients who had the so-called Philadelphia chromosome (Ph+), a genetic alteration discovered in Philadelphia in 1959 by Peter Nowell, MD, FAACR, and David A. Hungerford, PhD, and found in about 30 percent of adult ALL cases. It is associated with a worse prognosis for the disease. Allogeneic hematopoietic stem cell transplantation (HCT) using stem cells from a healthy person, usually a sibling, is a major treatment for the disease. However, relapse after transplant is common and remains the main cause of allogeneic HCT failure.

To assess the most recent trends in survival after post-HCT relapse, Bazarbachi and colleagues within the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT) conducted a retrospective, registry-based, multicenter study that included 899 adult patients with relapsed Ph+ ALL after allogeneic HCT from 2000 to 2019.

“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,” said first 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. “These large-scale real-world data can serve as a benchmark for future studies in this setting.”

A second allogeneic HCT within two years after relapse was performed in 13.9 percent of patients, resulting in a two-year OS from the date of the second transplant of 35.9 percent, with a progressive decrease in the two-year relapse incidence from the date of the second transplant (74 percent in the 2000-2004 period and 33 percent in the 2015-2018 period.)  

“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,” Dr. Bazarbachi said. “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 twenty years.”

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 Dr. Bazarbachi. “This effect is likely due to the greater efficacy of the novel targeted therapies.”

In recent years, new interventions aimed at reducing the risk of post-transplant relapse in Ph+ ALL patients have been developed, and new therapeutic strategies have become available for the management of post-transplant relapse, including newer-generation tyrosine kinase inhibitors, and immunotherapy such as blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa), and CAR-T cell therapy. In addition, due to higher donor availability and a progressive increase in the use of matched unrelated donors, second allogenic HCT as salvage therapy is also an option.

According to the authors, the improvements in supportive care and the use of novel therapeutics have played a role in this positive trend. However, one limitation of this retrospective study is the lack of detailed information on the treatment of post-transplant relapse and its impact on survival improvement, which remains to be investigated.