scholarly journals Superior Graft-Versus-Leukemia Effect in Haploidentical Transplantation Compared with HLA-Matched Sibling Transplantation for High-Risk Acute Myeloid Leukemia in First Complete Remission: A Prospective Multicentre Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3339-3339 ◽  
Author(s):  
Sijian Yu ◽  
Qifa Liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cohort Study ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Free Survival ◽  
Graft Versus Leukemia ◽  
Matched Sibling ◽  
First Complete Remission ◽  
Acute Myeloid

This study aimed to investigate graft-versus-leukemia (GVL) of haploidentical donor (HID) compared with HLA-matched sibling donor (MSD) for high-risk acute myeloid leukemia (H-AML) in first complete remission (CR1). One hundred and eighty-nine patients with H-AML in CR1 were enrolled in this multicentre prospective cohort study. Patients were assigned to groups transplanted with HID (n=83) or MSD (n=106) based on donor availability (biological randomization). The primary endpoint was the incidence of MRD positivity post-transplantation (post-MRD+). All post-MRD+ patients received preemptive interventions. The cumulative incidences of post-MRD+ were 18% and 42% in HID and MSD groups, respectively, (p<.001). Fifty-two patients received preemptive DLI, including 13 (16%) in HID and 39 cases (37%) in MSD groups (p=.001). Among HID and MSD groups, the 3-year cumulative incidence of relapse were 14% and 24% (p=0.101); the 3-year cumulative incidence of treatment-related mortality were 15% and 10% (p=0.368); the 3-year overall survival rates were 72% and 68% (p=0.687); the 3-year disease-free-survival were 71% and 66% (p=0.579); the 3-year graft-versus-host disease and relapse free survival were 63% and 43% (p=0.035), respectively. HID has a stronger GVL than MSD in H-AML patients. HID transplantation as post-remission therapy should be recommended as one of the optimal choices for H-AML in CR1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission

2019 ◽  
Vol 3 (12) ◽  
pp. 1826-1836 ◽  
Author(s):  
Armin Rashidi ◽  
Mehdi Hamadani ◽  
Mei-Jie Zhang ◽  
Hai-Lin Wang ◽  
Hisham Abdel-Azim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Calcineurin Inhibitor ◽  
Chronic Gvhd ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Conditioning Intensity ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P &lt; .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

Comparable Disease-Free and Overall Survival After “Well-Matched” Unrelated Donor and Matched Sibling Donor Transplantation in Acute Myeloid Leukemia with Adverse Risk Karyotype in First Complete Remission: A Report From the Acute Leukemia Working Committee of the Centre for International Blood and Marrow Transplant Research.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 526-526
Author(s):  
Vikas Gupta ◽  
Martin S. Tallman ◽  
Wensheng He ◽  
Brent Logan ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Allogeneic Hsct ◽  
Matched Sibling ◽  
Disease Free ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 526 In patients with acute myeloid leukemia (AML) in first complete remission (CR1), the indications for matched sibling donor (MSD) transplants and unrelated donor (URD) haemopoietic stem cell transplantation (HSCT) are different. We sought to determine the prognostic impact of donor type on the outcomes of AML with adverse risk karyotype in CR1, a high-risk AML population considered as a standard indication for MSD and URD HSCT. We evaluated the outcomes of 584 patients undergoing allogeneic HSCT for AML with adverse risk karyotype in CR1 between 1995 and 2006, reported to the CIBMTR. Adverse risk karyotype was defined according to SWOG/ECOG classification. Cytogenetics abnormalities were further classified as: complex karyotype (3 or more abnormalities), 32%; and Non-complex divided as abnormal chromosome 7, 25%; chromosome 5, 9%; MLL gene rearrangements, 18%; t (6;9), 5%; and others, 10%. 226 patients underwent MSD and 358 URD. URD were classified based on high resolution typing as:” well matched” [n=254 (71%)] with no known disparity at HLA A, B, C, DRB1; and, “partially matched” [n=104 (29%)] with one locus known or likely mismatched. Previous MDS was present in 19% and 14% had therapy-induced (t-AML). Conditioning regimens were myeloablative and reduced intensity in 74% and 26%, respectively. At 3 years treatment-related mortality (TRM) incidence was 28% (95% CI 24-31); relapse 36%(32-40); disease-free survival (DFS) 36%(32-41) and overall survival (OS) 39%(35-44). Multivariate analyses are summarized in the table. “Well matched” URD and MSD yielded similar DFS and OS, while outcomes were significantly inferior for “partially matched” URD. Cytogenetically defined subsets had similar outcomes. Evaluated as a time-dependent covariate, chronic GVHD had a significantly lower risk of relapse (RR 0.68, p=0.046), while acute GVHD had no effect (RR 0.99, p=0.96). “Well matched” URD and MSD lead to similar DFS and OS in AML CR1patients with adverse risk karyotype. The pool of patients who may benefit from graft-vs-leukemia effect generated with allogeneic HSCT may be considerably expanded with “well-matched” URD HSCT. If a suitable MSD is not availabel, “well-matched” URD should be strongly considered where a MSD HSCT would otherwise be undertaken. Disclosures: No relevant conflicts of interest to declare.

Clinical Relevance of IDH1 and IDH2 Mutations and Single Nucleotide Polymorphism (SNP) rs11554137 in Patients with Acute Myeloid Leukemia Treated with Stem Cell Transplant in First Complete Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4643-4643
Author(s):  
Hala Abalkhail ◽  
Naeem A. Chaudhri ◽  
Claudia Ulrike Walter ◽  
Hazzaa Al Zahrani ◽  
Randa Nounou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Snp Polymorphism ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 4643 Background: Mutations in the genes encoding for the cytosolic isocitrate dehydrogenase 1 (IDH1) and the mitochondrial version of this enzyme (IDH2) have been reported in acute myeloid leukemia (AML) and other types of cancer. Presence of these mutations in AML correlated with more aggressive disease in some studies, but other studies did not find significant correlation with outcome when patients were treated with intensive chemotherapy. The polymorphism at rs11554137 in IDH1 was reported to correlate with inferior outcome in cytogenetically normal AML patients. Most of the studies evaluating the prognostic relevance of IDH1, IDH2 and the rs11554137 polymorphism were reported in patients treated with standard chemotherapy. The prognostic significance of these markers is not fully studied when AML patients are treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the prognostic value of the IDH1, IDH2, and rs11554137 polymorphism in patients with AML treated with HSCT in first complete remission (CR1). Methods: Samples from 69 patients with AML were analyzed for mutations in IDH1, IDH2, and the SNP rs11554137 by direct sequencing. All patients were diagnosed with AML, treated with chemotherapy followed by HSCT in CR1. They included intermediate (N=42) and adverse (N=27) cytogenetic risk groups. Results: The R132H and the SNP C to T change at rs11554137 (silent G105) in IDH1 were detected in 5 (7%) and 6 (9%) of 69 AML patients. The IDH2 mutations (N=5; 7%) included R140Q, 172K, and T169A. Patients with IDH1 or IDH2 mutations did not differ significantly in their overall survival, event free survival, or time to relapse from those without mutation. In addition, the rs11554137 SNP polymorphism did not correlate with outcome in this group of AML patients. We also looked at the combination of mutations as compared with cytogenetic risk and found no difference in survival or event free survival based on IDH1 or IDH2 mutations or rs11554137 polymorphism in the intermediate cytogenetic risk group. Conclusion: The data suggests that HSCT after intensive chemotherapy in CR1 may neutralize the negative prognostic impact of IDH1 and IDH2 or the rs11554137 SNP polymorphism. However, the number of cases is relatively small and further studies with larger number of cases are needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparable Leukemia-Free Survival after Autologous Hematopoietic Cell Transplantation Versus HLA-Identical Sibling Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia in First Complete Remission: A Registry Study By the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2514-2514
Author(s):  
Motonori Mizutani ◽  
Masahiko Hara ◽  
Hiroyuki Fujita ◽  
Jun Aoki ◽  
Heiwa Kanamori ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Allogeneic hematopoietic cell transplantation (HCT) from a matched sibling donor (MSD) may provide a cure for acute myeloid leukemia in first complete remission (AML/CR1), although the procedure is associated with a higher rate of treatment-related mortality (TRM) than autologous HCT, and it remains uncertain which modality is preferable as post-remission treatment. We therefore conducted a retrospective registry-based analysis to compare the outcomes of patients with AML/CR1 receiving autologous peripheral blood (PB) grafts (n=398, median age: 47, range: 17-80) and those receiving allogeneic MSD bone marrow (BM) grafts (n=633, median age: 38, range: 16-73) or allogeneic MSD PB grafts (n=475, median age: 42, range: 16-74) between 1995 and 2011. Consequently, the 5-year overall survival (OS) rates for the autologous PB, allogeneic BM and allogeneic PB recipients were 62% (95% confidence interval [CI], 57-67%), 61% (95% CI, 57-65%; P=0.90) and 54% (95% CI, 49-59%; P=0.07), respectively (Fig. 1-A), and the 5-year leukemia-free survival (LFS) rates were 57% (95% CI, 52-62%), 58% (95% CI, 54-63%; P=0.49) and 51% (95% CI, 46-56%; P=0.12), respectively(Fig. 1-B). Meanwhile, the 5-year cumulative incidence of TRM was 8% (95% CI, 5-11%), 16% (95% CI, 13-19%; P=0.009) and 19% (95% CI, 15-23%; P=0.0001), respectively, while that of relapse was 35% (95% CI, 30-40%), 26% (95% CI, 22-29%; P=0.003) and 30% (95% CI, 26-35%; P=0.08), respectively. A multivariate analysis performed with autologous PB HCT as the reference showed a hazard ratio (HR) for OS of 0.93 (95% CI, 0.73-1.18; P=0.53) for allogeneic BM HCT and 1.08 (95% CI, 0.83-1.39; P=0.57) for allogeneic PB HCT and an HR for LFS of 0.86 (95% CI, 0.69-1.09; P=0.21) and 0.98 (95% CI, 0.77-1.24; P=0.85), respectively. Stratifying the patients according to cytogenetics (favorable, intermediate and poor) and age (<50 years and ≥ 50 years) did not influence the results. Accordingly, autologous PB HCT may be a viable alternative as post-remission therapy in patients with AML/CR1 in the absence of MSD. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5584-5590 ◽  
Author(s):  
Xiao-Jun Huang ◽  
Hong-Hu Zhu ◽  
Ying-Jun Chang ◽  
Lan-Ping Xu ◽  
Dai-Hong Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.5% ± 4.5%. Overall survival (OS) and disease-free survival (DFS) at 4 years were 64.5% ± 5.1% and 55.6% ± 5.0%, respectively. The cumulative incident of relapse for the HRD-HSCT group was significantly lower than that for the chemotherapy-alone group (12.0% ± 4.6% vs 57.8% ± 6.2%, respectively; P < .0001). HRD-HSCT resulted in superior survival compared with chemotherapy alone (4-year DFS, 73.1% ± 7.1% vs 44.2% ± 6.2%, respectively; P < .0001; 4-year OS, 77.5% ± 7.1% vs 54.7% ± 6.3%, respectively; P = .001). Multivariate analysis revealed postremission treatment (HRD-HSCT vs chemotherapy) and high WBC counts at diagnosis as independent risk factors affecting relapse, DFS, and OS. Our results suggest that HRD-HSCT is superior to chemotherapy alone as postremission treatment for AML.

Risk-Stratification Treatment Directed by Minimal Residual Disease Improves the Outcome of Acute Myeloid Leukemia with t(8;21) in First Complete Remission: Results of the AML05 Multicentre Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 139-139
Author(s):  
Honghu Zhu ◽  
Xiao-hui Zhang ◽  
Yazhen Qin ◽  
Hao Jiang ◽  
Dai-Hong Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Hazard Ratio ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
Risk Patients ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 139 Background Although patients with acute myeloid leukemia (AML) and the t(8;21) translocation generally have a favorable prognosis, relapse occurs in about 40% of cases and long-term (>5years) survival less than 50%. Patients with a KIT-mutation had an even higher relapse rate up to 70% and dismal survial. Once relapse, the outcome is extremely poor, even receiving allogeneic hematopoietic stem-cell transplantation (allo-HSCT).Therefore, rapidly identifying high-risk relapse patients and preemptively treating them with more aggressive therapy, such as HSCT, may decrease the chance of relapse and improve patient survival. We sought to improve outcome in patients with t(8;21) acute myeloid leukemia(AML) in first complete remission (CR) by applying risk-directed therapy that was based on measurements of minimal residual disease (MRD) by quantitative PCR during treatment. Methods From June 1,2005, to Dec 31, 2011, 137 patients with t(8;21) AML were enrolled at three centres. MRD was detected using quantitative PCR to detect the RUNX1/RUNX1T1 transcript. High-risk was defined by not achieving major molecular remission (MMR,> 3 log reduction of RUNX1/RUNX1T1 transcript from baseline) after second consolidation therapy or loss of MMR within 6 months since achieving MMR. Low-risk was defined by achieving MMR after second consolidation therapy and maintenance of MMR within 6 months thereafter. High-risk patients were recommended to receive allogeneic hematopoietic stem-cell transplantation (allo-HSCT) and low-risk patients to high-dose cytarabine-based consolidation chemotherapy. 116 patients who achieved CR and completed second consolidation were assigned to risk-directed therapy. Finally, sixty-nine patients actually received risk-directed therapy and 47 patients received a non risk-directed treatment for patients¡ bias. Findings With a median follow-time of 36 months in patients alive, risk-directed therapy and non risk-directed therapy achieved 5 year cumulative incidence of relapse(CIR) of 15.0%±4.7% and 57.5%±8.0%(p<0.0001), disease-free survival(DFS) of 74.7%±5.8% and 37.1%±7.4%(p<0.0001) and overall survival (OS) of 82.7%±5.1% and 49.8%±8.5% (p=0.002) (Figure 1). Allo-HSCT benefited high-risk as well as KIT-mutated but impaired low-risk patients' DFS and OS (all p<0.05) (Figure 2). Multivariate analysis revealed that MRD status (high-risk vs. low-risk) and treatment (risk-directed vs. no risk-directed) were independent prognostic factor for relapse(hazard ratio 8.85, 95% CI 2.05–38.13, p=0.003; 0.26, 95% CI 0.12–0.61, p=0.002), DFS(hazard ratio 9.32, 95% CI 2.21–39.3; p=0.002; 0.36, 95% CI 0.17–0.75, p=0.007) and OS (hazard ratio10.53, 95% CI 1.41–78.83; p=0.022; 0.37, 95% CI 0.15–0.93, p=0.035).KIT-mutation was an independent prognostic factor for relapse(hazard ratio 2.12, 95% CI 1.01–4.48, p=0.049) but not for DFS and OS. Interpretation Risk-stratification treatment directed by MRD could improve the outcome of AML with t(8;21) in first complete remission. Allo-HSCT benefits high-risk as well as KIT-mutated but impairs low-risk patients¡ survival. Disclosures: No relevant conflicts of interest to declare.

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