Outcomes with preemptive donor lymphocyte infusions after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes: A systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19014-e19014
Author(s):  
Syed Ather Hussain ◽  
Atif N khan ◽  
VENKATA S THAMMINENI ◽  
Muhammad Nauman Riaz ◽  
Moazzam Shahzad ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Acute Myeloid

e19014 Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) but relapse and graft versus host disease (GVHD) remain the most common challenges. Donor lymphocyte infusion (DLI) is the infusion in which lymphocytes from the original stem cell donor are infused, after the transplant, to augment an anti-tumor response or to ensure that the donor stem cells remain engrafted. In this systematic review and meta-analysis, we focused at outcomes of preemptive DLI in AML and MDS. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) PubMed, CINAHL, Cochrane, and Clinical trials.gov were searched. We included 8 out of 214 articles, excluding duplicates and non-relevant articles. The quality of the included studies was evaluated using NIH quality assessment tool. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2) to report the efficacy of preemptive DLI. We pooled the experimental arms results of the included trials using the inverse variance method and logit transformation. Between studies, the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 222 patients who received preemptive DLI. Median age, time since transplant and DLI dose were 48 (32-58) years, 82 (7-160) days and 1.4 million cells/kg respectively. CR and PR were 43% (95%CI 0.14-0.78, I293%, n= 127) and 61% (95%CI 0.40-0.78, I262%, n= 81) respectively. After median follow up of 46 months, non-relapsed mortality (NRM) was 52% (95%CI 0.38-0.65, I249%, n = 121). OS was reported 72% (95%CI 0.62-0.80, I20%, n= 100). Acute and chronic GVHD incidence after DLI was 20% (95% CI 0.13-0.29, I24%, n= 105) and 25% (95% CI 0.08-0.56, I2=79%, n=101) respectively (Table). Conclusions: Preemptive DLI significantly improves OS with a low incidence of acute and chronic GVHD. However, NRM was seen in more than half of all the patients and prospective studies are needed to evaluate safety of preemptive DLI. Outcomes with preemptive DLI (n= 222).[Table: see text]

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 Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis

2021 ◽  
Author(s):  
Andrés R. Rettig ◽  
Gabriele Ihorst ◽  
Hartmut Bertz ◽  
Michael Lübbert ◽  
Reinhard Marks ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Risk Marker ◽  
Single Center ◽  
Hematopoietic Stem ◽  
Acute Myeloid ◽  
Donor Lymphocyte Infusions

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML.

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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