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2126 Evidence-Based Choice of Conditioning Regimen for Hematopoietic Stem Cell Transplantation (HSCT) in Acute Leukemia: The Italian Cellular Therapy and Stem Cell Transplant Group (GITMO) Guidelines

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, AML, Acute Myeloid Malignancies, Clinical Practice (Health Services and Quality), Diseases, Lymphoid Malignancies, Myeloid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Alessandra Picardi, MD1*, Monia Marchetti, MD, PhD2*, Luca Castagna3*, Mattia Algeri, MD4*, Stella Santarone, MD 5*, Marco Zecca, MD6*, Michele Malagola, MD7, Nicola Mordini8*, Franca Fagioli, MD, PhD9*, Angelo Michele Carella, MD10*, Raffaella Greco, MD11*, Francesco Onida, MD12, Domenico Pastore, MD13*, Michele Troiano14*, Anna Mussano15*, Federica Tangari16*, Gaspare Guglielmi17*, Adriana Balduzzi, MD18, Stefano Botti19*, Chiara Cannici20*, Martina Pitea21*, Fabio Ciceri, MD22*, Francesca Bonifazi23* and Massimo Martino, MD24*

1Stem Cell Transplant Program AORN Cardarelli, Naples and Biomedicine and Prevencion Department of Tor Vergata University, Rome, Naples / Rome, Italy
2Hematology & Transplant Unit, University Hospital SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy
3Bone Marrow Transplantation Unit AOR Villa Sofia Cervello, Palermo, Italy
4Department of Hematology-Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children's Hospital, Rome, Italy
5Centro Trapianti Midollo Osseo; Azienda Sanitaria Locale di Pescara, Pescara, ITA
6Pediatric Hematology-Oncology,, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
7Clinical and Experimental Sciences, Brescia, BS, Italy
8Hematology, Azienda Ospedaliera S Croce e Carlo; Cuneo, Italy;, Cuneo, ITA
9Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, University of Turin, Turin, Italy
10Hematology and Bone Marrow Transplant Unit, IRCCS Fondazione Casa Sollievo della Sofferenza San Giovanni Rotondo, Foggia, Italy, San Giovanni Rotondo, Italy
11Unit of Hematology and Stem Cell Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy
12Hematology and BMT Unit - ASST Fatebenefratelli-Sacco - University of Milan, Italy;, Milan, Italy
13Hematology and Bone Marrow Transplant Unit, Brindisi, Italy, Brindisi, Italy
14Fondazione Casa Sollievo Della Sofferenza IRCCS, Radioterapia - San Giovanni Rotondo, Foggia, ITALIA;, Foggia, Italy
15Responsabile SS Radioterapia S.Anna - O.I.R.M.- SC Radioterapia U Città della Salute e della Scienza – Torino, Italy, Torino, Italy
16Unit of Clinical Pharmacy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy;, Roma, Italy
17Pharmacy Unit, AORN Cardarelli, Naples, Italy;, Napoli, Italy
18Fondazione IRCCS San Gerardo dei Tintori, Pediatric Hematopoietic Stem Cell Transplant Unit, Monza, Italy
19Haematology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Reggio Emilia, Italy
20Hematology Unit, AO SS Antonio e Biagio e Cesare Arrigo di Alessandria, Alessandria, Italy, Alessandria, Italy
21Trials Office GITMO Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia Cellulare, Bologna, Italy
22Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
23IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
24Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Stem Cell Transplant Program CIC 587, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli”, Presidio Morelli, Viale Europa, 8, Reggio Calabria, Italy

BACKGROUND

Conditioning regimens for acute myeloid (AML) and lymphoid (ALL) leukemia include a wide set of chemo-radiotherapy combinations capable of inducing a decline of bone marrow activity and thus favoring allogeneic stem cell engraftment and preventing leukemia relapse. Hematopoietic stem cell transplantation (HSCT) conditioning schedules include alkylating, non-alkylating drugs and, in some cases, total body irradiation (TBI). Drugs and/or TBI dose identify the intensity of conditioning regimen. Excessive heterogeneity of the clinical practices may limit the auditing and the correct interpretation of the outcomes. Therefore, in June 2023, GITMO started a project aimed at developing evidence-based guidelines selecting the most appropriate conditioning regimen for adult and pediatric patients receiving their first HSCT for AML or ALL in complete remission.

METHODS

The process adhered to the benchmark GRADE methodology for developing evidence-based recommendations. A methodologist and a chair leaded a nationwide panel of 12 adult hematologists, 4 pediatricians, 2 pharmacists, 1 pharmacologist, 2 transplant nurses and 2 radiotherapists. The panel broke down the target “population” into 4 subgroups: adult AML, children AML, adult ALL and children ALL. According to the EBMT Consensus (Spyridonidis 2020), a comparator was chosen for each of 3 “intensity” (TCI) classes and all the other conditioning regimens were tested as “interventions”. Critical outcomes included non-relapse-mortality (NRM), cumulative incidence of relapse (CIR) and engraftment rate. Evidence was retrieved by EMBASE and PubMed queries: relevant articles and extracted data to summary-of-evidence tables were selected. Evidence-to-decision tables were discussed and recommendations approved during 6 virtual meetings. An External Review Panel was conveyed including members of 5 scientific societies (AIRO, AIEOP, GITMO, SIFO, SIF).

RESULTS

In the first phase of the project the Panel faced high-TCI regimens for AML and completed 7 pairwise interventions comparisons versus BuCy, e.g. the standard “comparator”. The Panel agreed on 3 evidence-based statements for high-TCI conditioning in adult AML: BuCy or TreoFluMel were recommended, while TBICy was recommended against, except for specific scenarios such as extramedullary disease, dendritic cell leukemia and young people at very high risk that would be worthy of clinical trials. Overall 4 conditioning regimens were not supported by sufficient evidence in adult AML: BuFluArac and BuFLuMel were therefore judged to be better investigated by further studies, while TBICyVP16 and BuCyVP16, were not judged to be worth further research. The Panel agreed on a single evidence-based statement for high TCI in pediatric AML: patients were recommended to receive BuCyMel rather than BuCy and TBICy was recommended against. No evidence could be retrieved supporting BuFluMel in pediatric AML, but no research was deemed to be devoted to this regimen. In the second phase of the project the Panel faced high-TCI in ALL and completed 7 pairwise interventions comparisons versus TBICy, e.g. the standard “comparator”. The Panel agreed on 3 evidence-based statements for adults: both TBIVP16 and BuCy can be suggested as a valid alternative to TBICy in case of matched HSCT, while TBIFlu is preferred in case of mismatched donor because of PT-CY as GVHD prophylaxis. One evidence-based statement was elaborated for high-TCI in pediatric subset: TBIVP16 association is recommended in case of matched related or unrelated allogeneic HSCT, however TBICy represents a valid alternative option. Haploidentical pediatric HSCT was excluded because in vitro T cell depletion is used in most Italian Transplant Program (TP). Two negative statements were also included for both adult and pediatric ALL: TBI-based conditioning should not incorporate two drugs and there are no sufficient data to recommend clofarabine-treosfulfan as alternative to TBICy regimen. Recommendations for low and intermediate-TCI are in progress.

DISCUSSION

A wide variety of conditioning regimens are currently used based on clinical features, TP habits and expertise. However, GRADE method can be applied in such a complex framework and help the selection of those conditioning regimens supported by sufficient evidence that can be identified as solid backbones for the built of National Practice Guidelines.

Disclosures: Picardi: MSD: Other: Advisory board; AMGEN: Speakers Bureau; NOVARTIS: Other: Advisory board; GILEAD: Speakers Bureau; MEDAC: Speakers Bureau. Marchetti: GILEAD: Consultancy; MSD: Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Algeri: Vertex Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee Membership. Onida: Menarini-stemline: Speakers Bureau; kyowa: Speakers Bureau; MEDAC: Speakers Bureau; takeda: Speakers Bureau. Balduzzi: Neovii: Speakers Bureau; Medac: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Botti: Jazz healthcare Italy: Speakers Bureau; Roche: Speakers Bureau. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees. Bonifazi: SANOFI: Honoraria; MSD: Honoraria, Speakers Bureau; KITE: Honoraria, Speakers Bureau; NEOVII: Honoraria; TAKEDA: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau; AMGEN: Honoraria, Speakers Bureau; PFIZER: Honoraria, Speakers Bureau; JAZZ PHARMACEUTICALS: Honoraria, Speakers Bureau; bms: Honoraria, Speakers Bureau. Martino: abbvie: Honoraria, Speakers Bureau; pfizer: Honoraria, Speakers Bureau; JAZZ PHARMACEUTICALS: Honoraria, Speakers Bureau; astellas pharma: Honoraria, Speakers Bureau; takeda: Honoraria, Speakers Bureau; sanofi: Honoraria, Speakers Bureau; msd: Honoraria, Speakers Bureau; novartis: Honoraria, Speakers Bureau; Roche: Other: attending meetings; medac: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau; gilead: Honoraria, Speakers Bureau.

*signifies non-member of ASH