Non Interventional Prospective Study On The Effect Of 48 Gene Variants On Different Endpoints After Allogeneic Stem Cell Transplantation For Patients With Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3287-3287
Author(s):  
Michael Koldehoff ◽  
Dietrich W. Beelen ◽  
Ahmet H. Elmaagacli
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Prospective Study ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Gene Variants ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Background Single-nucleotide polymorphisms (SNPs) are molecular markers that vary significantly among different populations. Our group has earlier reported about different genetic associations of SNPs with GvHD and/or outcome after allogeneic hematopoietic stem cell transplantation (HSCT) in different retrospective studies. Here we profiled SNPs in a non interventional prospective study (Trial No DRKS00004352) about the influence of different endpoints for patients (pts) with acute myeloid leukemia who underwent allogeneic HSCT between June 2011 and February 2013. Methods We analyzed simultaneously 48 different genes of every patient/donor pairs in whole blood by high-throughput LightCycler® 480 real-time PCR-system using high resolution melting optimization strategies. Results In this cohort 20 pts received grafts from HLA-identical siblings (23%), 42 pts from matched (48%) and 26 pts from mismatched (30%) unrelated donors. Transplant consisted of unmanipulated peripheral blood stem cells (n=79, 90%) or bone marrow (n=9, 10%). Of all pts (n=88, male 48 pts and female 40 pts), 18 (21%) had relapsed and 28 (32%) died of May 2013. In the cohort the occurrence of acute GvHD (aGvHD) grade 2-4 was influenced by gene variants on recipient side of CYP 2C9 (39% vs 72%, p<0.04), IL16 (53% vs 31%, p<0.01) and MTHFR 677, 1298 (31% vs. 52%, p<0.05). Furthermore, the occurrence of severe aGvHD ≥3 was influenced by GSTP1 A/G (3% vs 20%, p<0.04), LAT (6% vs 17%, p<0.02), MBL2 codon 550 (3% vs 22%, p<0.03), and VEGF 405 G/C (15% vs 7%, p<0.02). There was no significant correlation between different gene variants of pts and the estimate for 1-year overall survival (OS). We found that the rate of 1-year none-relapse mortality (NRM) was associated favorably with the detection of variants of NOD2 genes (0% vs 26%, p<0.04) and MBL codon 220 (7% vs 32%, p<0.05) and associated adversely with the detection of variants of LAT (16% vs 34%, p<0.03). The estimate 1-year relapse rate was associated adversely with the detection of variants of IL 10 592 C/A (15% vs 45%, p<0.05) and associated favorable with the detection of variants of TLR9 genes (40% vs. 10%, p<0.02) Conclusions These preliminary results suggest that different gene variants have influence on the transplant settings in pts with acute myeloid leukemia. Disclosures: Off Label Use: HCG will be discussed as new therapy for chronic GVHD.

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 Magnesium levels and outcome after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

2020 ◽  
Author(s):  
Linus Angenendt ◽  
Isabel Hilgefort ◽  
Jan-Henrik Mikesch ◽  
Bernhard Schlüter ◽  
Wolfgang E. Berdel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Myeloid Leukemia ◽  
Epstein Barr Virus Infection ◽  
Hematopoietic Stem ◽  
Acute Myeloid

AbstractLow intake of magnesium has been associated with the occurrence of lymphomas and decreased magnesium levels suppress the cytotoxic function of T cells and natural killer cells in patients with “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia” (XMEN) syndrome. These cell types are also important mediators of immune-mediated effects after allogeneic hematopoietic stem cell transplantation. Here, we show that high posttransplant magnesium levels independently associate with a lower incidence of relapse, a higher risk of acute graft-versus-host disease, and a higher non-relapse mortality in 368 patients with acute myeloid leukemia from our center. Magnesium serum levels might impact on donor-cell-mediated immune responses in acute myeloid leukemia.

scholarly journals CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingya Cui ◽  
Chongsheng Qian ◽  
Nan Xu ◽  
Liqing Kang ◽  
Haiping Dai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cell Therapy ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Car T ◽  
Acute Myeloid

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.

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