Allogeneic HSCT effective for high-risk acute lymphoblastic leukemia
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SALT LAKE CITY — Allogeneic hematopoietic stem cell transplantation appeared effective for patients with high-risk subtypes of acute lymphoblastic leukemia, according to study results.
More than half of patients achieved long-term survival, results presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR showed.
The findings also demonstrated that patients who received timely referral to transplant achieved longer OS and DFS.
“The take-home message for the clinical community definitely is the importance of early referral,” Melhem Solh, MD, medical director for the cellular therapy program at Northside Hospital, told Healio. As soon as patients are in complete remission, they should be referred straight to transplant, because our data shows how delays affect OS.”
Background and methodology
Relapse is the primary reason for treatment failure among adults with ALL.
Allogeneic HSCT has extended survival for patients with high-risk subtypes, but success depends on multiple disease-, patient- and transplant-related factors, according to study background.
Solh and colleagues aimed to assess the factors that affected post-transplant survival among adults with ALL.
The analysis included 153 consecutive patients (median age, 46 years; range, 14-70; 50% male) who underwent their first allogeneic HSCT at their institution from 2008 to 2020.
About three-quarters (73%) had intermediate-risk disease and 27% had high/very high-risk disease.
More than one-third (36%) had Philadelphia chromosome (Ph)-positive disease and 9% had Ph-like disease. Ten percent had received blinatumomab (Blincyto, Amgen) or inotuzumab ozogamicin (Besponsa, Pfizer) prior to transplant.
All patients underwent transplant in the outpatient setting. Only those who developed complications were admitted.
Most patients (72%) were in first complete remission at time of transplant
The majority of patients (84%) received hyper-CVAD induction, and most (68%) achieved complete remission after one cycle.
Most patients had haploidentical donors (45%), followed by matched unrelated (31%) and matched related (24%). The most common graft source was peripheral blood stem cells (89%) and most patients (76%) underwent myeloablative transplant.
Median time from diagnosis to transplant was 157 days (range, 77-4,062).
Key endpoints included OS, DFS and relapse rate.
Researchers created a multivariable model for those three outcomes using disease, patient and transplant factors.
Results
Median follow-up after transplant was 58.8 months.
At 3 years after diagnosis, 67% of patients remained alive, 53% remained alive and disease free, and 30% had relapsed.
At 5 years after diagnosis, 57% of patients remained alive, 49% remained alive and disease free and 32% had relapsed.
“At 3 years, relapse becomes a very rare event, so transplant does get you to that curative intent plateau by that time,” Solh said during a presentation.
Researchers reported comparable outcomes among patients with Ph-positive, Ph-like and Ph-negative disease with regard to OS, DFS and relapse.
“The responses we saw in our data set are much better than what we have seen historically, so there is some improvement,” Solh told Healio. “The lack of difference between disease subtypes did not surprise us. The whole reason you do the transplant is so you can overcome the high-risk features, and that’s what we found.”
Multivariable analysis revealed associations between shorter OS and age 50 years or older (HR = 1.83; 95% CI, 1.11-3.01), male sex (HR = 1.66; 95% CI, 1.01-2.72) and time from diagnosis to transplant (HR for 9 months vs. < 9 months = 5.98; 95% CI, 3.39-10.55). Only time to transplant appeared associated with shorter DFS (HR = 5.9; 95% CI, 3.42-10.2) and higher risk for relapse (HR = 6.29; 95% CI, 3.2-12.38).
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Solh M, et al. Abstract 45. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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