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    Home > Active Ingredient News > Blood System > Transplant Cell Ther: Post-transplant Cyclophosphamide Therapy and Total Bone Marrow and Lymphatic Irradiation as a Conditioning Protocol Test in Patients with AML in Remission

    Transplant Cell Ther: Post-transplant Cyclophosphamide Therapy and Total Bone Marrow and Lymphatic Irradiation as a Conditioning Protocol Test in Patients with AML in Remission

    • Last Update: 2022-05-21
    • Source: Internet
    • Author: User
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    Graft-versus-host disease (GVHD) remains the leading cause of post-transplantation mortality and morbidity after allogeneic hematopoietic cell transplantation (alloHCT), adding a huge economic burden and affecting quality of life, thus, in patients with no increased risk of relapse.
    It is desirable to reduce the incidence of GVHD in patients with complete remission (CR) under these circumstances

    .

    In this study, researchers tested a new conditioning regimen, total bone marrow and lymphoid irradiation (TMLI) at 2000 cGy and post-transplant cyclophosphamide (PTCy) for the first or second CR.
    Patients with acute myeloid leukemia to reduce risk by using PTCy to treat chronic GVHD, while using escalated targeted radiomodulation prior to allogeneic transplantation to counteract a possible increased risk of relapse

    .

    2000 cGy of total bone marrow and lymphoid irradiation (TMLI) and post-transplant cyclophosphamide (PTCy) are used in acute myeloid leukemia patients with first or second CR to reduce the risk of chronic GVHD by using PTCy while at the same time.
    Use of upgraded targeted radiation modulation prior to allogeneic transplantation to counteract a possible increased risk of recurrence

    .

    The primary objective was to assess the safety/feasibility of combining a TMLI transplant conditioning regimen with a post-transplant high-dose cyclophosphamide (PTCy)-based GVHD prevention strategy by assessing the type, frequency, severity, attribution of adverse events, Time course, duration and complications including acute GVHD, infection and delayed neutrophil/platelet engraftment
    .

    Patient safety lead-in was performed first to ensure no unexpected toxicities, and expanded in the absence of dose-limiting toxicities (DLT)
    .
    The patient safety lead-in portion followed a 3+3 dose expansion/(de-)escalation rule based on observed toxicity at +30 days; TMLI started at 2000 cGy, with escalation to 1800 cGy considered

    .
    Following the safe lead-in portion, an expansion cohort of up to 12 additional patients will be studied

    .
    TMLI was administered on days -4 to 0 at 200 cGy twice daily

    .
    The radiation dose delivered to the liver and brain was maintained at 1200 cGy

    .
    Cyclophosphamide at 50 mg/kg per day for GVHD prophylaxis was administered on days +3 and +4 after alloHCT; tacrolimus was administered until day 90 and then tapered

    .

    Figure 1: Treatment regimen
    .
    *TMLI starting dose (dose grade 1): 2000cGy (200cGy twice daily); dose level-1: 1800cGy

    .
    **For unrelated donor products, stem cell infusion can be performed within two days of the last dose of TMLI (time based on product availability)

    .
    ***Initiate tacrolimus 1mg continuous intravenous (CIV) to +90 days; G-CSF 5mcg/kg daily +5 days to ANC at least 1500/mm
    3 for 3 consecutive days

    Figure 1: Treatment regimen
    .
    *TMLI starting dose (dose grade 1): 2000cGy (200cGy twice daily); dose level-1: 1800cGy

    .
    **For unrelated donor products, stem cell infusion can be performed within two days of the last dose of TMLI (time based on product availability)

    .
    ***Initiate tacrolimus 1 mg continuous intravenous (CIV) to +90 days; G-CSF 5mcg/kg daily +5 days to ANC of at least 1500/mm3 for
    3 consecutive days
    Figure 1: Treatment regimen
    .
    *TMLI starting dose (dose grade 1): 2000cGy (200cGy twice daily); dose level-1: 1800cGy

    .
    **For unrelated donor products, stem cell infusion can be performed within two days of the last dose of TMLI (time based on product availability)

    .
    ***Initiate Tacrolimus 1mg continuous intravenous (CIV) to +90 days; G-CSF 5mcg/kg daily +5 days to ANC at least 1500/mm
    3 for 3 consecutive days
    3

    Figure 2: Acute GVHD, Chronic GVHD and GRFS

    Figure 2: Acute GVHD, Chronic GVHD and GRFS

    Figure 3: Progression-Free Survival, Overall Survival, Relapse-Free Survival, and Relapse-Free Mortality

    Figure 3: Progression-Free Survival, Overall Survival, Relapse-Free Survival, and Relapse-Free Mortality

    The results suggest that among 18 patients with a median age of 40 years (range 19-56 years), the highest-grade toxicities were Grade 2 Bearman's bladder toxicity and stomatitis
    .
    No grade 3-4 Bearman toxicity or toxicity-related deaths were observed

    .
    The cumulative incidence of acute GVHD (aGVHD) grades 2-4 and moderate to severe chronic GVHD was 11.
    1% and 11.
    9%, respectively

    .
    At a median follow-up of 24.
    5 months, the two-year OS and recurrence-free survival rates were estimated to be 86.
    7% and 83.
    3%, respectively

    .
    The 2-year disease recurrence rate was 16.
    7%

    .
    The estimated 2-year NRM is 0%

    .
    The 2-year GVHD/relapse-free survival (GRFS) rate was 59.
    3% (95%CI: 28.
    8-80.
    3)

    .

    Overall, this chemotherapy-free conditioning regimen, along with PTCy and tacrolimus, was safe with no non-relapse mortality (NRM), and preliminary results suggest an improvement in GRFS rates
    .
    On the basis of these encouraging preliminary results, the research team will conduct a larger phase 2 trial to confirm these data: to assess the 1-year primary goal of GRFS; to estimate the cumulative incidence of acute and chronic GVHD, and to estimate the OS, without leukemia Survival (LFS) to recurrence, and NRM as secondary goals

    .

    This chemotherapy-free conditioning regimen, along with PTCy and tacrolimus, is safe with no non-relapse mortality (NRM), and preliminary results suggest improved GRFS rates

     

    Original source:

    Original source:

    Stein AS, Malki MMA, Yang D, Palmer JM, Tsai NC, Aldoss I, Ali H, Aribi A, Artz A, Dandapani S, Farol L, Hui S, Liu A, Nakamura R, Pullarkat V, Radany E, Rosenthal J , Salhotra A, Sanchez JF, Spielberger R, Marcucci G, Forman SJ, Wong J.
    Total Marrow and Lymphoid Irradiation with Post-Transplant Cyclophosphamide for Patients with AML in Remission.
    Transplant Cell Ther.
    2022 Apr 6:S2666-6367(22) 01190-3.
    doi: 10.
    1016/j.
    jtct.
    2022.
    03.
    025.
    Epub ahead of print.
    PMID: 35398328.

    Stein AS, Malki MMA, Yang D, Palmer JM, Tsai NC, Aldoss I, Ali H, Aribi A, Artz A, Dandapani S, Farol L, Hui S, Liu A, Nakamura R, Pullarkat V, Radany E, Rosenthal J , Salhotra A, Sanchez JF, Spielberger R, Marcucci G, Forman SJ, Wong J.
    Total Marrow and Lymphoid Irradiation with Post-Transplant Cyclophosphamide for Patients with AML in Remission.
    Transplant Cell Ther.
    2022 Apr 6:S2666-6367(22) 01190-3.
    doi: 10.
    1016/j.
    jtct.
    2022.
    03.
    025.
    Epub ahead of print.
    PMID: 35398328.
    Stein AS, Malki MMA, Yang D, Palmer JM, Tsai NC, Aldoss I, Ali H, Aribi A, Artz A, Dandapani S, Farol L, Hui S, Liu A, Nakamura R, Pullarkat V, Radany E, Rosenthal J , Salhotra A, Sanchez JF, Spielberger R, Marcucci G, Forman SJ, Wong J.
    Total Marrow and Lymphoid Irradiation with Post-Transplant Cyclophosphamide for Patients with AML in Remission.
    Transplant Cell Ther.
    2022 Apr 6:S2666-6367(22) 01190-3.
    doi: 10.
    1016/j.
    jtct.
    2022.
    03.
    025.
    Epub ahead of print.
    PMID: 35398328.


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