PMID- 35646299 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2040-6207 (Print) IS - 2040-6215 (Electronic) IS - 2040-6207 (Linking) VI - 13 DP - 2022 TI - Relapsed acute lymphoblastic leukaemia after allogeneic stem cell transplantation: a therapeutic dilemma challenging the armamentarium of immunotherapies currently available (case reports). PG - 20406207221099468 LID - 10.1177/20406207221099468 [doi] LID - 20406207221099468 AB - While survival rates in paediatric acute lymphoblastic leukaemia (ALL) nowadays exceed 90%, systemic ALL relapse, especially after haemopoietic stem cell transplantation (HSCT), is associated with a poor outcome. As there is currently no standardized treatment for this situation, individualized treatment is often pursued. Exemplified by two clinical scenarios, the aim of this article is to highlight the challenge for treating physicians to find a customized treatment strategy integrating the role of conventional chemotherapy, immunotherapeutic approaches and second allogeneic HSCT. Case 1 describes a 2-year-old girl with an early isolated bone marrow relapse of an infant KMT2A-rearranged B-cell precursor ALL after allogeneic HSCT. After bridging chemotherapy and lymphodepleting chemotherapy, chimeric antigen receptor (CAR) T-cells (tisagenlecleucel) were administered for remission induction, followed by a second HSCT from the 9/10 human leukocyte antigen (HLA)-matched mother. Case 2 describes a 16-year-old girl with a late, isolated bone marrow relapse of B-cell precursor ALL after allogeneic HSCT who experienced severe treatment toxicities including stage IV renal insufficiency. After dose-reduced bridging chemotherapy, CAR T-cells (tisagenlecleucel) were administered for remission induction despite a CD19(-) clone without prior lymphodepletion due to enhanced persisting toxicity. This was followed by a second allogeneic HSCT from the haploidentical mother. While patient 2 relapsed around Day + 180 after the second HSCT, patient 1 is still in complete remission >360 days after the second HSCT. Both cases demonstrate the challenges associated with systemic ALL relapse after first allogeneic HSCT, including chemotherapy-resistant disease and persisting organ damage inflicted by previous therapy. Immunotherapeutic approaches, such as CAR T-cells, can induce remission and enable a second allogeneic HSCT. However, optimal therapy for systemic ALL relapse after first HSCT remains to be defined. CI - (c) The Author(s), 2022. FAU - Poyer, Fiona AU - Poyer F AUID- ORCID: 0000-0002-3393-9706 AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Fureder, Anna AU - Fureder A AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Holter, Wolfgang AU - Holter W AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Peters, Christina AU - Peters C AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Boztug, Heidrun AU - Boztug H AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Dworzak, Michael AU - Dworzak M AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Engstler, Gernot AU - Engstler G AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Friesenbichler, Waltraud AU - Friesenbichler W AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Kohrer, Stefan AU - Kohrer S AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Luftinger, Roswitha AU - Luftinger R AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Ronceray, Leila AU - Ronceray L AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Witt, Volker AU - Witt V AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Pichler, Herbert AU - Pichler H AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria. FAU - Attarbaschi, Andishe AU - Attarbaschi A AD - Department of Pediatric Haematology and Oncology, St. Anna Children's Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria. LA - eng PT - Case Reports DEP - 20220523 PL - England TA - Ther Adv Hematol JT - Therapeutic advances in hematology JID - 101549589 PMC - PMC9134426 OTO - NOTNLM OT - acute lymphoblastic leukaemia OT - allogeneic haematopoietic stem cell transplantion OT - immunotherapy OT - relapse COIS- Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: AA has received honoraria for lectures, consultancy, or advisory board participation from the following companies: Jazz Pharmaceuticals, Amgen, Novartis, MSD, Servier, and Gilead. He has received compensation for travel expenses from Jazz Pharmaceuticals. MD has received honoraria for lectures, consultancy, or advisory board participation from the following for-profit companies: Beckman-Coulter, Daiichi Sankyo, and Servier. The following for-profit companies have supported research conducted by MD with benefits or honoraria made to his institution: Beckman-Coulter, Becton-Dickinson, Exbio, and Jannsen. BH has received compensation of travel expenses from AOP Orphan Pharmaceuticals, AMGEN, and Amomed Pharma. The remaining authors declare no conflict of interest. EDAT- 2022/06/02 06:00 MHDA- 2022/06/02 06:01 PMCR- 2022/05/23 CRDT- 2022/06/01 11:34 PHST- 2022/01/16 00:00 [received] PHST- 2022/04/19 00:00 [accepted] PHST- 2022/06/01 11:34 [entrez] PHST- 2022/06/02 06:00 [pubmed] PHST- 2022/06/02 06:01 [medline] PHST- 2022/05/23 00:00 [pmc-release] AID - 10.1177_20406207221099468 [pii] AID - 10.1177/20406207221099468 [doi] PST - epublish SO - Ther Adv Hematol. 2022 May 23;13:20406207221099468. doi: 10.1177/20406207221099468. eCollection 2022.