scholarly journals An Anti-CD300f Antibody Drug Conjugate Depletes Hematopoietic Stem Cells and Primary Acute Myeloid Leukemia (AML): Facilitating a Targeted Conditioning Regimen for Allogeneic Stem Cell Transplantation in AML

2020 ◽  
Vol 26 (3) ◽  
pp. S33
Author(s):  
Edward Abadir ◽  
Pablo Silveira ◽  
Robin Gasiorowski ◽  
Murari Ramesh ◽  
Adelina Romano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Antibody Drug Conjugate ◽  
Hematopoietic Stem ◽  
Acute Myeloid ◽  
Antibody Drug

scholarly journals Immunomodulation with Azacytidine and Donor Lymphocyte Infusion Following Sequential Conditioning Allogenic Stem Cell Transplantation Improves Outcome of Unfavorable AML

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4600-4600
Author(s):  
Magalie Joris ◽  
Delphine Lebon ◽  
Amandine Charbonnier ◽  
Pierre Morel ◽  
Berengere Gruson ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Acute Myeloid

Background : Patients with acute myeloid leukemia in relapse or refractory to induction therapy have dismal prognosis. Response rates to common salvage regimens are low and allogenic hematopoietic stem cell transplantation is the only curative option. Several studies have demonstrated that salvage chemotherapy with sequential conditioning could reduce leukemia relapse risk with an acceptable toxicity profile for unfavorable acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). [1] Therefore, we decided to assess this procedure in our center at Amiens University Hospital. Methods We conducted a monocentric retrospective study, including 53 patients aged over 18 years undergoing a hematopoietic stem cell transplant (HSCT) with sequential conditioning between January 2012 and December 2018, for relapse/refractory AML or high risk MDS. 44 (83%) patients received sequential conditioning containing clofarabine (SET-RIC) or Amsacrine (FLAMSA) and 9 (17%) thiotepa based (TEC-RIC) with post-transplant cyclophosphamide for mismatched donors. Patients who were GVHD free after immunosuppressors withdrawal received immunomodulation as relapse prevention with azacytidine 37.5mg/m²/day 5 days every 4 weeks for 12 cycles with 3 donor lymphocyte infusions (DLI) alterned between azacytidine cycles. Results The median age was 52 years (range 18-70). Before conditioning, 48 patients had unfavorable AML with ELN intermediate score refractory to at least one course of induction therapy or in relapse, or unfavorable ELN score; 5 patients had high risk MDS with complex karyotype. 32 patients (60,5%) had active disease and 21 (39,5%) were in complete remission (CR) including 12 with positive MRD. 13 (24,5%) patients had HLA-identical sibling donors, 27 (51%) match unrelated donors (MUD), 4 (7,5%) mismatch unrelated donors (MMD) and 9 (17%) haploidentical donors. Majority of patients (90,5%) received peripheral blood stem cell (PBSC) PBSC with median CD34+ count of 7,94.106/kg (1,84-8,44). Acute GvHD prophylaxis with Ciclosporin A, in combination with Mycophenolate mofetil for MUD/MMR/Haplo, was withdrawal with a median time of 90 days. With a median follow-up of 40 months, overall survival (OS) at 1 and 2 years was 68% and 52%. Median OS was 18,7 months (0-72,4 months) and median disease free survival (DFS) was 14,9 months (0-72,4 months). 17 patients (32%) experienced relapse after HSCT with a median time from HSCT to relapse of 6 months (1-35 months). 22 (41,5%) of patients presented with grade I-II acute graft versus host disease (GVHD) and 6 (11,3%) with grade III IV aGVHD . GVHD free relapse free survival (GRFS) at 1 and 2 years was 53% and 34,2%. One-year cumulative incidence of disease related death and non-relapse mortality was 12,6% and 17% respectively. 19 patients received immunomodulation with 5 Azacitidine and DLI if no GVHD occurred within day 120. OS was 79 % in the 19 patients receiving DLI. In univariate analysis immunomodulation post HSCT (Figure 1) was significantly associated with overall survival and leukemia free survival (p=0,0164 and p=0,0359 respectively) but not the disease status before HSCT (p=0,7). Immunomodulation administration with azacytidine and DLI was not significantly associated with cGVHD occurrence (p=0.31). Benefit of immunomodulation OS persisted in multivariate analysis (p=0.0284). Conclusion: Sequential conditioning regimen on refractory AML with secondary immunomodulation with azacytidine and DLI shows very good results with an acceptable toxicity profile in unfavorable AML. We achieve very good OS and DFS whatever disease status before HSCT. GRFS is also encouraging comparing to previously report datas [1]. Reference: [1] Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire. Decroocq et al. Am J Hematol 2018 ;93 :416-423. Figure 1 Disclosures No relevant conflicts of interest to declare.

Duration to Engraftment Requires Significantly Much More Time in Myelodysplastic Syndrome (MDS) Patients as Compared to Acute Myeloid Leukemia (AML) Patients Following Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5326-5326
Author(s):  
Menachem Bitan ◽  
Michael Y. Shapira ◽  
Igor B. Resnick ◽  
Benjamin Gesundheit ◽  
Irena Zilberman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Normal hematopoiesis is characterized by the balanced interplay between hematopoietic stem cells and the cells and molecules that forms part of the microenvironment in which blood cell production takes place. Myelodysplastic syndrome (MDS) marrow stroma cells are known to fail in supporting the growing of normal stem cells. We therefore retrospectively analyzed the duration to engraftment of absolute neutrophil count (ANC) ≥0.5 x 109/L and ≥1.0 x 109/L and the time interval to platelet recovery of ≥20 and ≥50 x 109/L in 42 MDS patients as compared to 42 patients suffering from primary acute myeloid leukemia (AML), following allogeneic stem cell transplantation (SCT). Significant shorter time to engraftment was documented in AML as compared to MDS patients in all 4 parameters. These results hold true even if we sub-grouped the patients according to gender, age, with the age of 50 years old being the cutoff between young and elderly patients, or when the donor was related to the patient. Moreover, sub-grouping the patients from each diagnosis according to the conditioning regimens that were given prior to transplantation revealed the same significant better results for the AML patients when received a non-myeloablative regimen. To the best of our knowledge, this is the first time that such a comparison is being made. We suggest that duration to engraftment in MDS patients takes significantly longer time and this may influence and worsen their course of transplantation in terms of morbidity as well as mortality.

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.

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