Prospective Evaluation of Azacitidine Maintenance Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5476-5476 ◽  
Author(s):  
Harinder Gill ◽  
Albert Kwok Wai Lie ◽  
Yok Lam Kwong ◽  
Anskar Y.H. Leung
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Poor Risk ◽  
Acute Myeloid

Abstract Introduction and aim. Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is a major cause of treatment failure and is associated with a poor prognosis. Overall survivals are around 50% at 5 years following allogeneic HSCT in intermediate and high risk AML. Survivals remain less than 20% in poor-risk and very poor-risk patients based on the cytogenetic profile. Thus, prevention of relapse following allogeneic HSCT remains an unmet clinical need. Low-dose azacitidine maintenance post-HSCT has been shown to augment graft-versus-leukemia effect and may prolong survivals. We aim to prospectively evaluate the effect of azacitidine maintenance following allogeneic HSCT in high risk AML and MDS. Method. Consecutive patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in remission following first allogeneic HSCT or second allogeneic HSCT (from the original donor) were recruited. High risk AML in this study comprised patients with poor risk karyotype, secondary AML transformed from underlying MDS, presence of fms-like tyrosine kinase 3-internal tandem duplication (FLT3 -ITD) and non-remission before HSCT. Azacitidine was administered at 100mg daily for 3 days per cycle every 28 days until progression or a maximum of 8 cycles. The clinicopathologic and treatment characteristics were determined. The occurrence of graft-versus-host disease (GVHD) was determined. DNA chimerism was determined in the bone marrow before the initiation of azacitidine, after 4th and 8th cycles of azacitidine and at 1 year. DNA chimerism was determined by quantification of polymorphic short tandem repeat sequences. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier analysis. Results. Thirty-four patients with high-risk AML (N=31) and MDS (N=3) were recruited. The median duration of follow-up was 14 months (range: 2 - 44 months). Twenty-two patients received azacitidine maintenance after first allogeneic HSCT, whereas 12 patients received azacitidine maintenance after a second allogeneic HSCT from the same donor following relapse from a first allogeneic HSCT For patients receiving azacitidine after first HSCT, at a median follow-up of 18.5 months (range: 5- 36 months), the median PFS was not reached, and the median OS was 32 months (95% confidence interval [C.I.]: 24.85-39.15). The 24-month PFS and OS were 66.1% and 73.2% respectively. Acute and chronic GVHD occurred in 7 (31.8%) and 17 patients (77%). For patients receiving azacitidine after second HSCT, at a median follow-up of 14 months (range: 9 - 46 months), the median PFS and OS were 9 months (95% C.I.:6.94-11.04) and 14 months (range: 11.77 - 16.23 months). The 24-month PFS and OS were 25% and 14% respectively. Acute and chronic GVHD occurred in 1 (8.3%) and 5 (41.7%) patients respectively. In both groups, 100% donor chimerism was achieved during azacitidine maintenance. Conclusion. Azacitidine maintenance following first allogeneic HSCT resulted in favorable 2-year survivals in selected patients with high-risk AML and MDS. Nevertheless, survivals were poor despite azacitidine maintenance after second allogeneic HSCT from the same donor. Full donor chimerism was maintained during azacitidine maintenance. Disclosures No relevant conflicts of interest to declare.

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 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.

scholarly journals Prognostic Prediction of Novel Risk Scores (AML-DRG and AML-HCT-CR) in Acute Myeloid Leukemia Patients with Allogeneic Hematopoietic Stem Cell Transplantation

2021 ◽  
Author(s):  
Weijie Cao ◽  
Xiaoning Li ◽  
Ran Zhang ◽  
Zhilei Bian ◽  
Suping Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Predictive Accuracy ◽  
Risk Groups ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Acute Myeloid

Abstract Purpose We aimed to validate and prove the novel risk score models of acute myeloid leukemia (AML)-specific disease risk group (AML-DRG) and AML-Hematopoietic Cell Transplant-composite risk (AML-HCT-CR) in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (AHCT). Methods One hundred twenty-three AML (non-APL) patients underwent AHCT was enrolled in this study. Patients were stratified into 3 AML-DRG and 4 AML-HCT-CR risk groups. Of the 123 patients, 57 (46.3%) were females, and the median age was 31 years (range 12 to 62 years). All patients received myeloablative conditioning. Median follow-up was 46 months (range 1 to 94 months). AML-DRG and AML-HCT-CR score models were applied with the overall survival (OS) and progression-free survival (PFS) analysis after the clinical follow-up. Results For the AML-DRG model, the 3-year OS in the low, intermediate and high-risk groups were 65.4%, 34.9% and 8.3%, respectively (p<0.001). The corresponding 3-year PFS were 64.0%, 34.9% and 8.3% (p<0.001). The OS predictive accuracy measured by C-index was 0.680. In the AML-HCT-CR model, the 3-year OS in the low, intermediate, high and very high-risk groups were 65.4%, 52.0%, 11.1% and 8.3%, respectively (p<0.001). The corresponding 3-year PFS were 64.0%, 52.0%, 11.1% and 8.3% (p<0.001). The OS predictive accuracy measured by C-index was 0.705. The AML-DRG and AML-HCT-CR models significantly predicted cumulative incidence of relapse (p=0.002; p=0.005). But both scores were not associated with NRM (p=0.314; p=0.095). Univariate analysis showed that the AML-DRG model could better stratify AML patients into different risk groups compared to the AML-HCT-CR model. Multivariate analysis confirmed that prognostic impact of AML-DRG and AML-HCT-CR models on post-transplant OS was independent to age, sex, conditioning type, transplant modality, and stem cell source (p<0.001; p<0.001). Conclusions The AML-DRG and AML-HCT-CR models can be used to effectively predict post-transplant survival in patients with AML receiving AHCT in our center. Compared to AML-HCT-CR score, the AML-DRG score allows better stratification and improved survival prediction of AML patients post-transplant.

Feasibility of Allogeneic Hematopoietic Stem Cell Transplant for High Risk FLT3-ITD Mutant Patients with Acute Myeloid Leukemia in CR1- a Real Word Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4694-4694
Author(s):  
Ankit J. Kansagra ◽  
Hassan B Alkhateeb ◽  
Mehrdad Hefazi ◽  
Fevzi Yalniz ◽  
William J Hogan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Median Time ◽  
Real World ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hct ◽  
Acute Myeloid

Background: Hematopoietic stem cell transplantation (HCT) remains the most effective postremission therapy for high-risk acute myeloid leukemia (AML). FMS-like tyrosine kinase3 (FLT3) mutations occur in about 30% of patients with cytogenetically normal AML. FLT3-ITD (internal tandem duplications) mutations are associated with short-lived remissions and poor outcomes. These adverse effects can be offset by allogeneic HCT in first complete remission (CR1). We carried out this study to get a real world perspective on feasibility of allogeneic HCT in CR1 for FLT3-ITD mutant AML patients. Methods: The Mayo Clinic AML database was queried for all patients that had tested positive for the FLT3 ITD, from January 2003 to December 2014. 75 patients were identified, of which 28 (37%) underwent allogeneic HCT in CR1. 12 were excluded as they were transplant ineligible from an age standpoint, 6 patients actually had MDS and 2 were excluded for primary induction failure. Clinical and outcomes data were abstracted retrospectively. Results: 29 patients were included in the final analysis, with a median age of 57 years (range 21-68), 38% males. Median time from diagnosis to last follow up was 339 days. 24(83%) had normal cytogenetics. 26(90%) received treatment with anthracycline + cytarabine based therapy, 3(10%) were enrolled on a clinical trial. 25(87%) patients went on to receive consolidation therapy. 22 (75%) of the patients relapsed after achieving a CR1, with a median time to relapse of 134 days (range 27-1710 days). Only 8 (26%) of the 22 patients were able to achieve a CR2 with salvage chemotherapy, of which 6 (75 %) successfully underwent allogeneic HCT.2 (25%) out of 8 patients received FLT3 inhibitor in 1st relapse. We then assessed the reasons why relapsed patients did not undergo HCT in CR1. The most common being; relapse during evaluation/work up for HCT in 8(27%) patients, 5 (17%) had comorbidities that precluded HCT, 3 (10%) were never referred for HCT due to personal preferences. At last follow up 19(65%) patients were dead. Conclusion: While allogeneic HCT is an effective consolidative strategy for FLT3 ITD mutant AML patients, in the real world, a large number are not transplanted in CR1 due to delays in donor search and transplant scheduling strategies resulting in disease relapse. Effective strategies to avoid delays in scheduling, rapid donor searches and the use of alternative donor sources are much needed for these patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Intravenous Busulfan-Based Myeloablative Conditioning Is Comparable to TBI-Based Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Recipients with Acute Myeloid Leukemia: A Nationwide Retrospective Study From the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1922-1922
Author(s):  
Takuya Yamashita ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
Kazuteru Ohashi ◽  
Saiko Kurosawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Conditioning Regimens ◽  
Acute Myeloid

Abstract Abstract 1922 In allogeneic hematopoietic stem cell transplantation (HSCT) for recipients with acute myeloid leukemia (AML), cyclophosphamide (Cy) combined with total body irradiation (TBI) (Cy+TBI) is the most common myeloablative conditioning (MAC) regimen, but busulfan (Bu) in combination with Cy (Bu+Cy) has been an alternative to Cy+TBI since early 1980s. But as oral Bu has a problem of interpatient variation in intestinal absorption, intravenous Bu (ivBu) has been developed and substituted for Bu in conditioning regimens for HSCT. For the last decade, fludarabine (Flu)-based regimens with the addition of cytotoxic agents such as Bu or melphalan (L-PAM) have been developed as reduced-intensity conditioning (RIC) regimens. After the introduction of ivBu, Flu+ivBu has become one of the common RIC regimens. In Japan, ivBu was introduced in 2006 and have been widely used as a part of conditioning regimens. In this nationwide retrospective study, we evaluated the clinical outcomes of allogeneic HSCT for AML, especially focusing on ivBu-based conditioning regimens. The study population included HSCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of adult patients with AML who received first allogeneic HSCT between 1975 and 2010. There were 9,396 recipients selected according to this criterion. Then, we excluded 345 (3.7%) cases from the study because of missing key variables. A total of 9,051 recipients were evaluated in this study. Median age at transplant was 43 years (range, 16–82), and 41.8% (n=3,785) were female. Types of transplant included bone marrow transplantation from sibling donor (RBMT) (n=1,978, 21.9%), peripheral blood stem cell transplantation from sibling donor (RPBSCT) (n=1,411, 15.6%), bone marrow transplantation from unrelated donor (UBMT) (n=3,321, 36.7%) and cord blood transplantation from unrelated donor (CBT) (n=1,728, 19.1%). MAC regimens were applied to 80.2% (n=7,259) of recipients and RIC regimens to 19.8% (n=1,792), according to the definitions proposed by the NMDP and the CIBMTR in 2007. These MAC regimens included Bu+Cy-based (12.4% of all MAC regimens), Cy+TBI-based (50.0%) and ivBu+Cy-based (5.6%) regimens. RIC regimens consisted mainly of Flu+Bu-based (27.6% of all RIC regimens), Flu+L-PAM-based (24.1%) and Flu+ivBu-based (19.5%) regimens. Median follow-up of survivors was 1,437 days (range, 26–8,344). In MAC setting, overall survival (OS) of HSCT recipients with ivBu+Cy-based regimens did not show the significant difference between that with Bu+Cy or Cy+TBI-based ones in RBMT (p=0.168), RPBSCT (p=0.236) and UBMT (p=0.604). But in CBT, Cy+TBI was significantly superior to Bu+Cy (p=0.004). Though the cumulative incidences of relapse (RI) were similar among recipients with these three regimens, the cumulative incidence of non-relapse mortality (NRM) with Bu+Cy was significantly higher than with Cy+TBI in CBT (p=0.049). In RIC setting, OS of recipients with Flu+ivBu-based regimens was comparable to that with Flu+Bu or Flu+L-PAM-based ones regardless of the type of transplant. RIs with these three regimens were almost equivalent, but NRM with Flu+ivBu-based was significantly lower than that with Flu+L-PAM-based in UBMT (p=0.023). In the multivariate analysis for OS, ivBu+Cy-based regimens did not have significant impacts regardless of the type of transplant, but Flu+ivBu-based regimen had a significantly favorable impact in RBMT (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.23–0.99). In the multivariate analysis for NRM, Flu+ivBu-based regimen had a significantly reduced risk compared with Flu+L-PAM in RBMT (HR 0.32, 95%CI 0.11–0.95) and UBMT (HR 0.46, 95%CI 0.25–0.83). These data indicates that ivBu+Cy-based and Cy+TBI-based MAC regimens have almost equivalent efficacy profiles for OS, RI and NRM, and Flu+ivBu-based RIC regimens can reduce the risk of NRM compared with Flu+Bu and Flu+L-PAM-based ones in allogeneic HSCT for recipients with AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Suk-young Lee ◽  
Naoki Kurita ◽  
Koichiro Maie ◽  
Masanori Seki ◽  
Yasuhisa Yokoyama ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

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.

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