Post-Transplant Relapse in Patients Transplanted with Active Acute Myeloid Leukemia (AML) - Treatment Options and Outcomes at a Large AML Referral Center
Authors: Ronnacker Julian , Urbahn Marc-Andre , Reicherts Christian , Kolloch Lina , Berning Philipp , Call Simon , Floeth Matthias , Marx Julia , Mikesch Jan-Henrik , Schliemann Christoph , Lenz Georg , Stelljes Matthias 
Published: December 2024

Introduction: Allogeneic hematopoietic stem cell transplantation (alloSCT) is the only potentially curative treatment option for patients (pts) with relapsed or refractory acute myeloid leukemia (r/r AML). Although survival is still inferior to pts transplanted without active disease, recent advances such as the introduction of sequential conditioning regimens have improved the prognosis for this high-risk pt population. However, in case of relapse after alloSCT, the prognosis of these pts remains poor and pts are often assigned to individualized treatment approaches, which show significant variation between centers. In this retrospective study, we investigated outcomes of 67 pts transplanted with active AML who experienced either measurable residual disease (MRD) or hematologic relapse after alloSCT.

Methods: We reviewed pts who received their first alloSCT with active AML at our center between 2014 and 2024. Of these, 67 pts experienced either hematologic or measurable residual disease relapse after alloSCT. Measurable residual disease (MRD) relapse was defined as the persistence/recurrence of defined molecular or cytogenetic aberrations or a decrease in CD34+ donor cell chimerism &lt; 95%. Time-to-event variables were calculated from the day of relapse using the Kaplan-Meier method.

Results: Median age of relapsed pts was 61 (range 31-74) years and median follow-up from relapse was 26 months. Of these, 42 pts experienced an isolated MRD relapse without evidence of hematologic relapse at a median of 4 months after alloSCT, and 25 pts experienced hematologic relapse without prior MRD relapse at a median of 7 months after alloSCT. Of the pts with isolated MRD relapse (some of which later progressed to hematologic relapse), 37 (88%) had a decrease in CD34+ donor cell chimerism to a median of 78% (range 0-94); 23 (55%) had a persistence (n = 7) or recurrence (n = 16) of defined genetic aberrations. Two-year overall survival (OS) of pts with MRD relapse was 45% (95% CI, 31-64%) and 2-year relapse-free survival (RFS) was 27% (95% CI, 16-46%). Baseline variables such as age, genetic risk, comorbidity scores or donor type showed no association with survival on uni- and multivariable regression analysis. A total of 23 pts (55%) with MRD relapse received donor lymphocyte infusions (DLI), with 4 pts receiving DLI in combination with azacitidine. Thirteen pts (57%) achieved MRD-negative remission as best response after DLI, 3 pts (13%) achieved a stable disease (MRD-positive remission), and 7 pts (30%) experienced rapid progression to overt relapse. One-year OS from MRD relapse in DLI pts was 73% (95% CI, 57-94%). Among pts who did not receive DLI, 8 pts received azacytidine either alone (n=4), in combination with lenalidomide (n=1), venetoclax (n=1) or azacitidine followed by gilteritinib (n=2). Of these, 3 pts showed a treatment response (time to progression &gt; 8 weeks) and estimated 1-year OS of non-DLI treated pts from MRD relapse was 50%. The remaining pts received best supportive care (BSC, n = 4), tapering of immunosuppressive drugs only (n = 3), or salvage treatment in case of progressive disease (n = 4). Among the 25 pts who experienced a hematologic relapse without a prior MRD relapse, estimated 1-year OS was 24% (95% CI, 12-48%). Treatment included HMA-based regimens (n = 6), intensive salvage chemotherapy (n = 4), DLI / targeted therapies (n = 5), and BSC (n = 10). Age was the only baseline variable which was significantly associated with survival in pts with hematologic relapse on univariable analysis. A total of 5 pts proceeded to a second alloSCT.

Conclusion: Our data suggest that in the event of MRD relapse in pts transplanted with active AML, rapid implementation of salvage treatments has curative potential. When available, DLI can achieve MRD-negative remissions in more than half of the pts. However, in case of hematologic relapse, the prognosis is poor and long-term survival is in most cases limited to pts who can undergo an early second alloSCT.