A transplant offers a chance of a cure from leukemia, but when the transplant is not successful, such patients are left with few other options and a poor prognosis. But the management of such patients has been improving, and over the past 20 years, this has led to a steady improvement in survival rates for adult patients with relapsed Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic cell transplantation (HCT).
The improved survival was shown in a retrospective, registry-based multicenter study published online January 12 in Clinical Cancer Research
“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 [of these patients] was dismal,” lead author Ali Bazarbachi, MD, PhD, professor of medicine, American University of Beirut, Lebanon, said in a statement.
“This study represents the largest analysis to date assessing trends over time and predictive factors for outcome of relapsed Ph+ ALL after allo-HCT [and] we observed a major progressive improvement in OS from posttransplant relapse in [these] patients…likely reflecting the efficacy of posttransplant salvage strategies,” the authors observe.
Data for the study was obtained by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT), a working group made up of over 600 transplant centers that are required to report all consecutive HCTs and follow-ups once a year.
A total of 809 adult patients with Ph+ ALL who had relapsed between 2000 and 2019 following allo-HCT were included in the analysis. Median age at transplantation for the cohort was 44 years, while the median age at relapse was 43.4 years
Over the 20-year interval, there was a progressive increase in patient age at the time of transplantation from 40.6 years to 46.1 years (P = .007), the investigators note.
Other patient characteristics also changed over time, as shown in the following table.
|Use of matched unrelated donors||34.5%||56%||P = .0002|
|Use of peripheral blood stem cells||60.3%||84.5%||P < .0001|
|Progressive decrease in the use of total body irradiation||73%||53%||P = .0002|
Improved Overall Survival
The median follow-up for surviving patients was 56 months, the authors note. For the entire cohort, 41.5% of patients were still alive 2 years after relapse. However, the 2-year overall survival (OS) increased from 27.8% for patients relapsing between 2000 and 2004 to 54.8% for patients relapsing in 2015–2019 (P = .001), despite the fact that patients’ age at relapse increased from 44 years to 56 years over the same time interval.
ALL was the cause of death in 68.5% of patients. Again, however, this picture changed over time. Original disease was the cause of death for 72.2% of patients who relapsed between 2000 and 2004, but ot was the cause of death for only 50% of those who relapsed between 2015 and 2019. Factors that favorably affected OS on multivariate analysis included a longer time from transplant to relapse (P = .0006), as well as the year of relapse, where patients who relapsed in the early years of the study period were more likely to die than patients who relapsed in the more recent years.
On the other hand, patient’s age at relapse negatively affected OS (P = .034). The use of a second allo-HCT as salvage therapy following the first relapse also declined over time, from 22% in the earliest study period to 16% in the latest. However, trends over time showed a progressive decrease in the incidence of relapse 2 years after the second transplant from 74% in 2000 to 2004 to 33% for 2015 to 2018 (P = .03).
An increased availability of either well-matched unrelated donors or haploidentical family donors both help facilitate more successful second allo-HCT as salvage therapy.
In addition, there has been an increase in the treatment options following relapse after transplantation in recent years.
Post-transplant pharmacologic interventions that reduce the risk of relapse in Ph+ ALL are now widely deployed, either using a prophylactic approach with tyrosine kinase inhibitor (TKI)–based maintenance therapy or a preemptive strategy based on regular minimal residual disease monitoring. Moreover, newer-generation TKIs, including blinatumomab (Blincyto) and inotuzumab ozogamicin (Besponsa) as well as the novel CAR T-cell therapies, have also helped with better management of post-transplant relapse, the authors comment.
The study received no funding support. The authors have disclosed no relevant financial relationships.
Clin Cancer Res. Published online January 12, 2022.
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