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

Author(s):  
kaixun hu ◽  
Mei Guo ◽  
Chang-Lin Yu ◽  
Jian-Hui Qiao ◽  
Qi-Yun Sun ◽  
...  

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.

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  

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.


Author(s):  
S. N. Bondarenko ◽  
I. S. Moiseev ◽  
I. A. Samorodova ◽  
T. L. Gindina ◽  
M. A. Kucher ◽  
...  

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.


2019 ◽  
Vol 18 (2) ◽  
pp. 11-21
Author(s):  
L. N. Shelikhova ◽  
M. A. Ilushina ◽  
K. V. Semiglazova ◽  
Zh. B. Shekhovtsova ◽  
D. A. Shasheleva ◽  
...  

Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.


2019 ◽  
Vol 8 (9) ◽  
pp. 1437 ◽  
Author(s):  
Weerapat Owattanapanich ◽  
Patompong Ungprasert ◽  
Verena Wais ◽  
Smith Kungwankiattichai ◽  
Donald Bunjes ◽  
...  

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.


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