The observed increase in patient age at the time of relapse makes the findings even more impressive because longer survival is typically associated with younger age at the time of relapse.
New research by the American Association for Cancer Research (AACR) has found that the 2-year overall survival (OS) rate for adult patients with acute lymphoblastic leukemia (ALL) carrying the Philadelphia chromosome and whose disease relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) has nearly doubled since 2004.
ALL is an aggressive hematological disease and the presence of the Philadelphia chromosome is associated with a worse prognosis. According to an AACR press release, this chromosome is found in approximately 30% of all adult patients with the disease.
Allogeneic HSCT is a procedure that transfers blood cells from a healthy donor to a patient who has received treatment with radiation or high doses of chemotherapy to kill the leukemic cells. This is considered a curative option for patients with ALL who are Philadelphia chromosome-positive, and especially for those with persistent minimal residual disease caused by a very small number of cancer cells that remain after treatment.
In some cases, however, the residual leukemic cells can escape the anticancer immune response induced by the transplanted immune cells and proliferate. Disease relapse after transplant is common and remains the predominant cause of transplantation failure.
In recent years, however, new interventions aimed at reducing the risk of post-transplant relapse 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. Furthermore, having a second allogeneic HSCT is also an option thanks to higher donor availability and a progressive increase in the use of matched unrelated donors, according to the AACR.
“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 first and corresponding author Ali Bazarbachi, MD, PhD, in the press release. “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.”
In order to assess the most recent trends in survival after post-transplant relapse, researchers conducted a retrospective, registry-based, multicenter study that included 899 adults with relapsed disease after a transplant over a period of 20 years. They found a significant improvement in the 2-year OS rate after relapse, which increased from 27.8% in patients who relapsed between 2000 and 2004 to 54.8% in patients who relapsed between 2015 and 2019.
The investigators also found that survival increased with the length of time between transplant and relapse. Notably, the survival improvement was observed despite a significant increase in patient age at the time of relapse, from 44 to 56 years of age.
According to the study, 13.9% of patients also received a second allogeneic HSCT within 2 years after relapse, resulting in a 35.9% 2-year OS from the date of the second transplant. There was also a progressive decrease in the 2-year relapse incidence from the date of the second transplant, from 74% in the 2000 to 2004 period to 33% in the 2015-2018 period.
The authors noted that the observed increase in patient age at the time of relapse makes the findings even more impressive because, typically, longer survival is associated with younger age at the time of relapse. Bazarbachi said this is likely explained by the greater efficacy of the novel targeted therapies.
“Our study represents the largest analysis to date assessing the outcomes and characteristics of patients with relapse Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplant, and our findings proved that the survival of these patients has significantly improved over time,” Bazarbachi said in the press release. “These large-scale real-world data can serve as a benchmark for future studies in this setting.”
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://www.aacr.org/about-the-aacr/newsroom/news-releases/survival-rate-of-adult-patients-with-relapsed-acute-lymphoblastic-leukemia-after-hematopoietic-cell-transplantation-has-steadily-increased-over-the-past-two-decades/