S137 EXABS-244-CT Should Patients with AML and Active Disease be Transplanted? Boglarka Gyurkocza, MD1,2,* 1Adult Blood and Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA 2Department of Medicine, Weill Cornell Medical College, New York, USA *Corresponding author: gyurkocb@mskcc.org Keywords Refractory or relapsed AML, allogeneic hematopoietic cell transplantation Introduction Approximately 10–40% of patients with newly diagnosed acute myeloid leukemia (AML) fail to achieve complete remission (CR) with induction therapy. Current guidelines support allogeneic hematopoietic stem cell transplantation (HCT) in patients with acute myeloid leukemia (AML) who achieve complete remission (CR) and are at high risk for relapse. Patients with AML who fail to achieve CR have a dismal prognosis, with 5-year overall survival rates of about 10%.1–3 Retrospective data suggest that durable remissions can be achieved in approximately 30% of patients with refractory or relapsed AML after allogeneic HCT. Recent prospective data from the phase III ASAP Trial also suggest that in patients with poor response after initial first induction therapy or relapsed AML watchful waiting and sequential conditioning prior to allogeneic HCT result in comparable CR rates as could be observed with salvage chemotherapy with high-dose cytarabine plus anthracycline. Material and Methods In this review, we summarize retrospective and prospective data on allogeneic HCT in patients with refractory or relapsed AML. We also aim to review factors associated with improved outcomes in this patient population and existing prognostic score systems, that might aid patient selection. Lastly, we explore novel transplant approaches that have the potential to improve outcomes in this patient population. Results In a more recent retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT) involving 3,430 patients with primary refractory or relapsed AML, Nagler et al. reported 2-year overall survival (OS) rates of 32.1% and 38.1% for patients undergoing allogeneic HCT from unrelated donors between 2000–2009 and 2010–2019, respectively, observing an improvement of outcomes over the last two decades.4 These results are consistent with previous retrospective analyses of allogeneic HCT in patients with refractory or relapsed AML.5–8 There is growing literature on the utilization of HLA-mismatched related and unrelated donors in this setting.9 Recognizing that patients with refractory or relapsed AML represent a heterogeneous population, several attempts have been made to identify variables associated with improved outcomes, to aid in the choice whether to proceed to allogeneic HCT.10,11 In an analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, Duval et al. identified the presence of circulating blasts, a mismatched unrelated donor, a related donor other than an HLA-matched sibling, a Karnofsky score less than 90%, and poor-risk cytogenetics as adverse risk factors. Using these five risk factors a prognostic score system, the “Duval Score” was developed: patients with a score of 0 had a 3-year OS of 42%, while correspondingly OS in patients with a score of >3 was only 6%.11 Our group aimed to identify novel risk factors associated with improved outcomes in an analysis presented at the 64th American Society of Hematology (ASH) Annual Meeting.12 The role of watchful waiting and sequential conditioning prior to allogeneic HCT was evaluated in a recent prospective, phase III randomized trial, also reported at the 64th American Society of Hematology (ASH) Annual Meeting by Stelljes et al.13 In this trial the authors found that patients with poor response after first induction therapy or relapsed AML did not benefit from salvage chemotherapy with high-dose cytarabine plus anthracycline prior to allogeneic HCT. In this patient population, watchful waiting and sequential conditioning prior to allogeneic HCT resulted in comparable CR rates and OS as those receiving salvage chemotherapy to induce remission. Early HLA-typing of AML patients and their family members (possibly at the time of diagnosis), conditioning regimens incorporating novel agents, such as briquilimab or 131I-apamistamab, engineered donor grafts and maintenance therapy with novel agents or cell therapeutics have the potential to improve disease-free and overall survival in this patient population through improved disease control. Conclusions In conclusion, retrospective and emerging prospective data show that allogeneic HCT performed in patients with refractory or relapsed AML can result in long-term disease-free survival in a proportion of patients. Allogeneic HCT should be considered
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