Cytogenetic, molecular factors predict prognosis among patients who relapse after allogeneic HSCT
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ORLANDO — Cytogenic and molecular factors can help predict prognosis of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allogeneic hematopoietic stem cell transplantation, according to retrospective study results presented at TCT | Transplantation & Cellular Therapy Meetings.
“Prognosis for patients with AML or myelodysplastic syndrome who relapse after transplant is very poor,” Corrado Zuanelli Brambilla, MD, of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, told Healio. “Time to relapse and type of relapse — minimal residual disease or morphologic relapse — were already known prognostic factors for post-relapse survival. We wanted to look at predictive or prognostic cytogenetic and molecular factors that correlated with those outcomes.”
The analysis included 148 patients (median age, 60 years; range, 24-78; 67.6% men) with AML (n = 104) or myelodysplastic syndrome (n = 44) who underwent allogeneic transplantation between 2010 and 2017 and subsequently relapsed.
More than half (58.8%) had Hematopoietic Cell Transplantation-specific Comorbidity Index scores of 3 or higher.
Patients with AML had undergone a median two prior lines of treatment (range, 1-6) and those with myelodysplastic syndrome had undergone a median one prior treatment (range, 0-2).
Study protocol allowed for any donor type and conditioning regimen. Sources could be bone marrow or peripheral blood stem cells.
Median time to relapse was 6 months (range, 1-61).
Median post-relapse OS was 6 months (95% CI, 4.8-8.8) in the overall cohort, although it was significantly longer among patients with AML than myelodysplastic syndrome (9.4 months vs. 5.3 months; P = .026).
Researchers identified the following factors associated with poorer post-relapse OS: morphologic relapse (vs. minimal residual disease, P = .00081), shorter time to relapse (0-6 months vs. 24+ months, P < .0001), p53 abnormality at relapse (P < .0001), complex/monosomal karyotype at relapse (P = .0033) and NPM1 mutation at relapse (P = .00052).
“We also saw, encouragingly, that outcomes after relapse are improving with time,” Brambilla told Healio.
Those who underwent transplant between 2017 and 2019 achieving better longer post-relapse survival than those who underwent transplant between 2010 and 2013 (P = .00054).
Approximately one-third of patients (n = 45) received either a second allogeneic HSCT (n = 28) or donor lymphocyte infusion (n = 17) after relapse. This additional therapy conferred a reduced risk for death after relapse (HR = 0.53; 95% CI, 0.32-0.87), and nearly half of patients (44.9%; 95% CI, 31.1-64.8) who received this second form of cell therapy survived 2 years.
“We tried to compare survival outcomes after transplant and after donor lymphocyte infusion, but we weren’t able to do that because of the relatively small number of patients,” Brambilla said. “One of the next steps would be to conduct a larger study, hopefully involving different centers, to see if we can identify specific cohorts for whom donor lymphocyte infusion is at least as effective as transplant and hopefully clarify the optimal indications for these second cell therapy strategies.” – by Mark Leiser
Reference: Brambilla CZ, et al. Abstract 130. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosure: Brambilla reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.
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