PMID- 35185899
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20220328
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Case Report: Preemptive Treatment With Low-Dose PD-1 Blockade and Azacitidine for 
      Molecular Relapsed Acute Myeloid Leukemia With RUNX1-RUNX1T1 After Allogeneic 
      Hematopoietic Stem Cell Transplantation.
PG  - 810284
LID - 10.3389/fimmu.2022.810284 [doi]
LID - 810284
AB  - Acute myeloid leukemia (AML) patients who develop hematological relapse (HR) 
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally 
      have dismal clinical outcomes. Measurable residual disease (MRD)-directed 
      preemptive interventions are effective approaches to prevent disease progression 
      and improve prognosis for molecular relapsed patients with warning signs of 
      impending HR. In this situation, boosting the graft-vs-leukemia (GVL) effect with 
      immune checkpoint inhibitors (ICIs) might be a promising prevention strategy, 
      despite the potential for causing severe graft-vs-host disease (GVHD). In the 
      present study, we reported for the first time an AML patient with RUNX1-RUNX1T1 
      who underwent preemptive treatment with the combined application of tislelizumab 
      (an anti-PD-1 antibody) and azacitidine to avoid HR following allo-HSCT. On day 
      +81, molecular relapse with MRD depicted by RUNX1-RUN1T1-positivity as well as 
      mixed donor chimerism occurred in the patient. On day +95, with no signs of GVHD 
      and an excellent eastern cooperative oncology group performance status (ECOG PS), 
      the patient thus was administered with 100 mg of tislelizumab on day 1 and 100 mg 
      of azacitidine on days 1-7. After the combination therapy, complete remission was 
      successfully achieved with significant improvement in hematologic response, and 
      the MRD marker RUNX1-RUNX1T1 turned negative, along with a complete donor 
      chimerism in bone marrow. Meanwhile, the patient experienced moderate GVHD and 
      immune-related adverse events (irAEs), successively involving the lung, liver, 
      lower digestive tract and urinary system, which were well controlled by 
      immunosuppressive therapies. As far as we know, this case is the first one to 
      report the use of tislelizumab in combination with azacitidine to prevent 
      post-transplant relapse in AML. In summary, the application of ICIs in MRD 
      positive patients might be an attractive strategy for immune modulation in the 
      future to reduce the incidence of HR in the post-transplant setting, but safer 
      clinical application schedules need to be explored.
CI  - Copyright (c) 2022 Tang, Zhou, Yan and You.
FAU - Tang, Yutong
AU  - Tang Y
AD  - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhou, Zhenyang
AU  - Zhou Z
AD  - Department of Radiology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
AD  - Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
FAU - Yan, Han
AU  - Yan H
AD  - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - You, Yong
AU  - You Y
AD  - Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Case Reports
PT  - Research Support, Non-U.S. Gov't
DEP - 20220202
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (RUNX1 Translocation Partner 1 Protein)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (RUNX1T1 protein, human)
RN  - 0KVO411B3N (tislelizumab)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Azacitidine/adverse effects
MH  - Core Binding Factor Alpha 2 Subunit/genetics
MH  - Fatal Outcome
MH  - Graft vs Host Disease/*etiology
MH  - Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Humans
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - Leukemia, Myeloid, Acute/genetics/*therapy
MH  - Male
MH  - RUNX1 Translocation Partner 1 Protein/genetics
MH  - Recurrence
MH  - Transplantation, Homologous
PMC - PMC8847388
OTO - NOTNLM
OT  - RUNX1-RUNX1T1
OT  - acute myeloid leukemia
OT  - allogeneic hematopoietic stem cell transplantation
OT  - graft-versus-host disease
OT  - graft-versus-leukemia
OT  - hypomethylating agents
OT  - immune checkpoint inhibitors
OT  - preemptive treatment
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/22 06:00
MHDA- 2022/03/29 06:00
PMCR- 2022/01/01
CRDT- 2022/02/21 06:01
PHST- 2021/11/06 00:00 [received]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/02/21 06:01 [entrez]
PHST- 2022/02/22 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.810284 [doi]
PST - epublish
SO  - Front Immunol. 2022 Feb 2;13:810284. doi: 10.3389/fimmu.2022.810284. eCollection 
      2022.