Effect of rhG-CSF Combined with Decitabine Prophylaxis on Relapse in High-Risk Acute Myeloid Leukemia Patients after Hematopoietic Stem Cell Transplantation: An Open-Label, Multicenter, Randomized, Controlled, Phase 2 Trial

2019 ◽  
Author(s):  
Lei Gao ◽  
Yanqi Zhang ◽  
Sanbin Wang ◽  
Peiyan Kong ◽  
Yi Su ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Phase 2 ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Randomized Controlled ◽  
Phase 2 Trial ◽  
Acute Myeloid

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

scholarly journals Stem Cells Micro-transplantation in Elderly Patients Aged Over 70 With Acute Myeloid Leukemia: a Multicenter, Prospective, Non-interventional Study

2021 ◽  
Author(s):  
kaixun hu ◽  
Mei Guo ◽  
Chang-Lin Yu ◽  
Jian-Hui Qiao ◽  
Qi-Yun Sun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Chemotherapy Group ◽  
Acute Myeloid

Abstract BackgroundThe treatment outcomes of elderly patients aged over 70 with acute myeloid leukemia (AML) have been very disappointing. In comparison, our designed HLA-mismatched hematopoietic stem cell micro-transplantation (MST) has achieved such encouraging treatment results in AML patients as might warrant further investigations of the outcomes of MST for the above mentioned patients. MethodsOne hundred and eleven patients aged 70-88 years were enrolled. Eighty patients were assigned to the high-risk MST or standard MST group according to high-risk prognostic factors. The other thirty-one patients were assigned to either the chemotherapy group or support group. After receiving induction chemotherapy with cytarabine and anthracycline, patients who achieved complete remission (CR) were given another 2 cycles of post-remission therapy with cytarabine. Each chemotherapy regimen was followed by donor stem cell infusion in the MST groups. ResultMST achieved an encouragingly high CR rate in patients (63.8%), even in high-risk patients (54%). It was significantly higher than that in the chemotherapy alone group. The 1-year overall survival (OS) of MST patients was 57.7% and was 68.6% in the high-risk and standard group, respectively, whereas the OS was only 37.3% in the chemotherapy group. The severe infection rate was 36% and 54% in MST and chemotherapy group. No GVHD was observed in MST patients. A larger updated T cell clones was observed in MST patients by T cell receptor repertoire analysis with a Next Generation Sequencing methodology. ConclusionsThese results suggested that MST is a safe and practical treatment regimen conducive to a longer-term survival for AML patients at a highly advanced age.

scholarly journals Comparison of the efficacy of chemotherapy and allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in first remission in adults

2015 ◽  
Vol 22 (3) ◽  
pp. 66-80
Author(s):  
S. N. Bondarenko ◽  
I. S. Moiseev ◽  
I. A. Samorodova ◽  
T. L. Gindina ◽  
M. A. Kucher ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
First Remission ◽  
Acute Myeloid

The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.

scholarly journals FLAMSA-RIC for Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (9) ◽  
pp. 1437 ◽  
Author(s):  
Weerapat Owattanapanich ◽  
Patompong Ungprasert ◽  
Verena Wais ◽  
Smith Kungwankiattichai ◽  
Donald Bunjes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1–76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7–145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9–70.2%) and 40.2% (95% CI, 28.0–53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1–64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3–32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4–53.9%). Approximately 29% of the patients suffered from grades 2–4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1–19.8%) and 21.1% (95% CI, 18.8–23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.

Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

2020 ◽  
Author(s):  
Yu-juan Xue ◽  
Pan Suo ◽  
Yi-fei Cheng ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Groups ◽  
Low Risk ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Pediatric Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

TP53 Mutations In Patients With High-Risk Acute Myeloid Leukemia Treated With Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 711-711
Author(s):  
Jan Moritz Middeke ◽  
Silvia Herold ◽  
Elke Rücker-Braun ◽  
Brigitte Mohr ◽  
Wolfgang E. Berdel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Tp53 Mutation ◽  
Chromosome 17 ◽  
Hematopoietic Stem ◽  
Tp53 Mutations ◽  
Donor Type ◽  
Acute Myeloid

Abstract Purpose The treatment success in patients (pts) with acute myeloid leukemia (AML) is very heterogeneous. Cytogenetic and molecular alterations present at diagnosis are strong prognostic factors, which have been used to individualize treatment. As shown by several groups, the subgroup of pts with deletion of the short arm of chromosome 17 are at high risk for treatment failure (e.g. Seifert, Leukemia 2009), which persists even after allogeneic hematopoietic stem cell transplantation (HSCT) (Middeke, Blood 2012; Mohr, Br J Haematol 2013). Besides allelic loss of TP53 located on the short arm of chromosome 17, other mechanisms of inactivation have been shown for this key tumor suppressor gene, most importantly missense point mutations or small deletions. These alterations have also been linked to poor outcome in AML after chemotherapy (Grossmann, Blood 2012). Here, we studied the impact of TP53 mutations on the outcome of AML pts with adverse cytogenetic risk treated with HSCT. Patients and Methods We selected AML pts with complex karyotype (CK), monosomy 7, monosomy 5/del5q and/or abnl(17p) who had received HSCT within 3 randomized controlled trials (NCT numbers 00180115, 00180102, and 00180167). All pts were treated with intensive induction chemotherapy and HSCT according to a risk adapted strategy. Complete sequencing of the TP53coding region was done using next generation sequencing (NGS) on a 454 GS Junior instrument (Roche) using the IRONII-study amplicon panel. Amplicons were generated from genomic DNA isolated at the time of diagnosis. Data analysis was done using the Sequence Pilot software package (JSI Medical Systems), a 10% cut-off was used for mutation calling. Nonsynonymous mutations were classified into bi-allelic TP53 mutations if detected allelic frequency as determined by NGS was >50% and mono-allelic TP53 mutations for frequencies between 10% and 50%. All samples with synonymous mutations or no detectable mutations according to the predefined cut-off of 10% were classified as TP53wild type (wt). Overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse-mortality (NRM) after HSCT were analyzed according to the mutational status. Results Samples from 97 pts with AML were analysed, the median age was 51 years (range 18 to 67), 83% suffered from de novo AML, while 13% had sAML and 3% therapy-related myeloid neoplasms. CK and monosomal karyotype (MK) were present in 61% and 42% of the pts, respectively. Twenty-nine pts (30%) had abnl(17p) detected by conventional karyotyping or FISH analysis. Twenty-six pts (27%) were treated with standard myeloablative conditioning (MAC) regimens while the remaining pts received reduced intensity conditioning (RIC). Donors were siblings in 36 pts (37%) and matched or mismatched unrelated donors in all other pts. Overall, TP53 mutations were found in 40 pts (41%). Twenty-eight (29%) pts had a bi-allelic TP53 mutation while 12 (12%) pts had a mono-allelic TP53 mutation. We identified 15 pts with TP53 mutations without abnl(17p). Four pts with abnl(17p) had wt TP53. Pts with TP53 mutations were significantly older than pts with wt TP53 AML (median age 55 vs. 43, p=.004). Donor type, type of conditioning and the rate of transplantation in first complete remission were not statistically different among pts with or without TP53mutations. With a median follow up of 67 months the three-year probabilities of OS and EFS for pts with wt TP53 were 33% (95% CI, 21% to 45%) and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (p=.002 and p=.007) for those with mutated TP53, respectively. CIR at three years was 42% for pts with wt TP53 and 60% for those with mutated TP53 (p=.05). NRM was not different in both groups. In multivariate analysis including age, donor type (sibling vs. all other), type of conditioning (RIC vs. MAC) and disease status (CR1 vs. advanced disease) only the TP53-mutation status had a significant influence on EFS (HR=1.72; p=.03). In our analysis, classification according to MK did not significantly influence OS, EFS, CIR or NRM. Conclusion In this cohort of pts with cytogenetic adverse risk abnormalities, who had received HSCT, TP53 mutations were present in 41% of the pts. OS and EFS were significantly worse in pts with mutated TP53. Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in pts with adverse karyotype AML. Disclosures: No relevant conflicts of interest to declare.

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