scholarly journals Extramedullary Disease at Diagnosis of Acute Myeloid Leukemia Does Not Influence Outcome of Patients Undergoing Allogeneic Hematopoietic Cell Transplant in First Complete Remission

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2020-2020
Author(s):  
Fotios V. Michelis ◽  
Hans A. Messner ◽  
Naheed Alam ◽  
Vikas Gupta ◽  
Dennis Dong Hwan Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Occurrence of extramedullary (EM) disease at diagnosis of acute myeloid leukemia (AML) has been associated with increased risk of relapse and worse outcomes post-chemotherapy. There is minimal data in the literature concerning the association with outcomes following allogeneic hematopoietic cell transplantation (HCT). The purpose of this single-centre study was to retrospectively investigate the impact of EM disease at diagnosis on the outcome of 303 patients with AML in first complete remission (CR1) that underwent HCT during the time period 2000-2013. Median age at HCT was 51 years (range 18-71), 151 (50%) patients were female. Myeloablative conditioning (MAC) was used in 202 (67%) patients, reduced-intensity (RIC) in 101 (33%) patients. Donors were related for 194 (64%) patients, unrelated for 109 (36%) patients. Grafts were peripheral blood stem cells (PBSC) in 253 (83%) patients and bone marrow in 50 (17%) patients. Median follow-up of patients alive was 63 months (range 12-168). Cytogenetics at diagnosis were available for 263 (87%) of patients, of which 16 (5%) were favorable, 185 (61%) were intermediate and 62 (20%) were unfavorable risk (MRC classification). Primary induction failure prior to achievement of CR was seen in 67 (22%) patients. In vivo T-cell depletion was performed in 71 (23%) patients. A total of 124 patients (41%) underwent HCT during the years 2000-2006 and 179 patients (59%) during the years 2007-2013. EM disease at diagnosis was seen in 39 patients (13%), of whom 11 patients had CSF disease, 7 patients had gingival infiltration and 5 patients had leukemia cutis. Univariate analysis for overall survival (OS) demonstrated that EM disease at diagnosis had no influence (HR=0.96 for EM, 95%CI=0.60-1.51, p=0.85, Figure 1). Multivariable analysis for OS including the previously described variables verified this observation. EM disease did not influence cumulative incidence of relapse (CIR) on univariate analysis (HR=0.94 for EM, 95%CI=0.45-1.96, p=0.86, Figure 2), and this also was confirmed on multivariable analysis. Moreover, EM disease did not influence cumulative incidence of non-relapse mortality on both univariate (HR=0.94 for EM, 95%CI=0.53-1.66, p=0.83) and multivariable analysis. In conclusion, EM disease at diagnosis of AML in patients achieving CR1, does not seem to influence outcomes post allogeneic HCT. This is significant in the consideration of allogeneic HCT for the treatment of this unfavorable subtype of AML. We are unable to comment on whether a similar percentage of patients with EM disease versus without EM disease, achieve CR1. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kim: Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

scholarly journals Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission after 5-Azacitidine and Venetoclax: A Multicenter Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3962-3962
Author(s):  
Oren Pasvolsky ◽  
Shai Shimony ◽  
Ron Ram ◽  
Avichai Shimoni ◽  
Liat Shargian-Alon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Hematopoietic Cell ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Intensive Group ◽  
Acute Myeloid

Abstract The therapeutic landscape for acute myeloid leukemia (AML) has evolved in recent years with the introduction of hypomethylating agents (HMA) and venetoclax in patients previously deemed unfit for curative - intent treatment. Some of these patients undergo allogeneic hematopoietic cell transplant (alloHCT), yet there are scarce data regarding transplantation outcomes. We conducted a multicenter nationwide retrospective cohort study to evaluate outcomes of patients with AML who underwent alloHCT in first CR (CR1) after frontline treatment with 5-azacitidine plus venetoclax (aza-ven group). In addition, we collected a historical control group of patients who achieved CR1 following first line intensive chemotherapy followed by alloHCT (intensive group). 24 patients in the aza-ven group were transplanted between 2019 and 2021. Compared to the intensive group, patients in the aza-ven group were older (median age 71.7 vs. 58.4 years, p <0.001), had higher incidence of therapy related AML and AML with antecedent hematologic disorder (p <0.001) and had more often adverse cytogenetics (p=0.022). They had a higher percentage of allografts from matched unrelated donors, and reduced intensity conditioning was more commonly used (Table 1). Median follow up was 8 (range, 0 to 25) months in the aza-ven group and 23 (range, 4 to 56) months in the intensive group. Estimated 12 months non relapse mortality was 19.1% in the aza-ven group and 11.8% in the intensive group (p=0.492). The estimated median relapse free survival (RFS) was not reached in the aza-ven group and was 19.3 months (CI 95% 1-38) in the intensive group. There was no difference between the two groups in 12 months RFS (58% and 54% in the aza-ven group and intensive group, respectively, p = 0.892). The estimated median survival of the aza-ven group was not reached and the 12 months overall survival (OS) rate was 63.2%. The estimated median survival of the intensive group was 50 months (CI 95% 5 - 96) and the 12 months OS rate was 70.8%. There was no statistical differences between the two groups regarding OS (p = 0.58). In a subgroup Cox regression analysis of the aza-ven group, adverse ELN 2017 risk category and HCT-CI score ≥3 were predictive of decreased RFS, both in univariate analysis (UVA) and in multivariate analysis (MVA) (HR 10.56, CI 95%1.64-68.1, p=0.013 and HR 6.43, CR 95% 1.34-30.75, p=0,02, respectively). Graft source (alternative vs. matched donor) and HCT-CI score ≥3 were predictive of decreased OS in UVA (HR 19.45, CI 95% 1.66-228.13, p= 0.018 and HR 5.93, CI 95% 1.13-31.05, p=0.03], yet in MVA neither of these factors retained their predictive value. The cumulative incidence of acute GVHD at 6 months was similar between groups: 58% in the aza-ven group vs. 62% in the intensive group (p=0.39). Likewise, there was no difference in the cumulative incidence of chronic GVHD at 12 months: 40% vs 42%, respectively (p=0.747) In conclusion, our data suggests that alloHCT for AML patients achieving first CR with aza-ven appears feasible, with short term post-transplant outcomes comparable to those expected after traditional intensive chemotherapy. Our results were collected in the real world setting, and patients in the aza-ven group were older and had inherently worse leukemia characteristics, including more secondary AML and more adverse cytogenetic features. Future research is warranted to decipher the true spectrum of AML patients who could benefit from remission induction with this less intensive regimen prior to alloHCT. Figure 1 Figure 1. Disclosures Ram: Gilead: Honoraria; Novartis: Honoraria. Wolach: Janssen: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Amgen: Research Funding; Novartis: Consultancy; Neopharm: Consultancy. Yeshurun: Astellas: Consultancy; Janssen: Consultancy.

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