Institutional Research Information System University of Turin

De Gobbi, Marco

American Journal of Hematology, 2025; 100:1902–1905https://doi.org/10.1002/ajh.700301902American Journal of HematologyCORRESPONDENCEOutcome of Patients With Acute Myeloid Leukemias or Myelodysplastic Syndromes After Relapsing From Allogeneic Stem Cell Transplantation: The GITMO AML/MDS- Relapse Registry StudyMalagola Michele1,2  |  Castagna Luca3  |  Matranga Domenica4  |  Radici Vera1,2 |  Farina Mirko1,2 |  Galli Marco1,2 |  Accorsi Buttini Eugenia5 |  Rubini Vicky6 |  Alati Caterina7 |  Bassi Simona8 |  Biffi Alessandra9 |  Borghero Carlo10 |  Busca Alessandro11 |  Nozzoli Chiara12 |  Carella Angelo Michele13 |  Cavattoni Irene14 |  Cerretti Raffaella15 |  Chiusolo Patrizia16  |  Cimminiello Michele17 |  Cuoghi Angela18 |  De Gobbi Marco19,20  |  Vincenzo Federico21 |  Galieni Piero22 |  Iori Anna Paola23 |  Olivieri Attilio24 |  Parma Matteo25 |  Patriarca Francesca26 |  Pavone Vincenzo27 |  Picardi Alessandra28 |  Piras Eugenia29 |  Polverelli Nicola30  |  Prezioso Lucia31 |  Rambaldi Benedetta32 |  Scalisi Elvira33 |  Selleri Carmine34 |  Skert Cristina35 |  Spina Alessandro36 |  Tecchio Cristina37 |  Oldani Elena32 |  Eliana Degrandi38 |  Domenico Russo1,2 |  Martino Massimo7Correspondence: Malagola Michele (michele.malagola@unibs.it)Received: 17 March 2025 | Revised: 27 June 2025 | Accepted: 8 July 2025Keywords: acute myeloid leukemia | allogeneic stem cell tansplantation | disease burden | myelodysplastic syndrome | relapseTo the Editor,Disease relapse represents the main cause of treatment fail-ure  after allogeneic stem cell transplantation (Allo- SCT) in Acute Myeloid Leukemia (AML) and myelodysplastic syndrome (MDS) patients [1]. Thus, minimal residual disease (MRD) mon-itoring following allo- SCT is a mainstay of good clinical prac-tice. The prognosis following relapse is dismal, and recently new treatment options, such as hypomethylating agents (HMAs) alone or in combination with venetoclax (VEN), have been used also in the setting of post- transplant disease relapse, but data from prospective trials are lacking [2].With the aim to describe the real- life management of AML/MDS post- transplant relapses in Italy, we conducted this retro-spective registry study, involving 33/63 (52%) transplant centers in Italy and including 859 cases of disease relapse registered between 2015 and 2021 (GITMO- AML/MDS relapse study; Clini calTr ials. gov: NCT06790680). All patients included in the registry provided informed consent for data registration in the PROMISE database. Clinically available data were extracted from the PROMISE database, and additional queries on the relapse event were submitted to each center to minimize miss-ing data.The probability of Overall Survival (OS) was estimated using the Kaplan–Meier method. Cox proportional hazards model and log- rank test were used to compare OS across groups. Sub- distribution hazard model and Gray's test were used to compare Treatment Related Mortality (TRM) and Relapse Mortality (RM) across groups. For non- proportional OS risks, interaction with time was modeled as an unrestricted smooth cubic spline function. No correction for non- proportional risks was applied in the Fine and Gray model. Statistical analysis was performed in R (https:// cran. r- proje ct. org/ ) [3].Table  1 reports the patients' and transplants' characteristics. The median age of the patients at transplant was 57.4 years (range 18.7–74.8). Ninety percent of the patients (n = 768) were affected by AML, and 507/859 (59%) received the transplant in first complete remission (CR), following one line of therapy in 48% of the cases. The donor was unrelated in 48% of the cases (n = 416), matched sibling in 28% of the cases (n = 242) and hap-loidentical in 23% of the cases (n = 197), and more than two thirds of the patients (75%) received peripheral blood stem cells (PBSC). The conditioning was myeloablative in 71% of the cases (n = 611) and graft versus host disease (GVHD) prophylaxis in-cluded anti- thymocytes globulin (ATG) or anti- T lymphocytes © 2025 Wiley Periodicals LLC.1903globulin (ATLG) in 70% of the cases (n = 600). At the time of dis-ease recurrence, 757/859 patients (88%) had hematological re-lapse (more than 5% of blast cells in the bone marrow), whereas 102/859 patients (12%) showed minimal residual disease pos-itivity or molecular mixed chimerism (either on CD34+ or mononuclear BM cells or on peripheral blood neutrophils and/or lymphocytes) (Figure  S1). Moreover, 647/859 patients (75%) received a treatment for the relapse. In detail, 558/647 patients (86%) were treated with evidence of morphological relapse (more than 5% BM blasts), whereas 89/647 patients (14%) were treated in a pre- emptive setting (MRD positivity and/or mixed chime-rism). HMAs±venetoclax therapy was the most frequently used salvage treatment (308/647 patients, 48%). 144/647 patients (22%) were treated with intensive chemotherapy at relapse, and 76/647 patients (12%) received an anti- FLT3 inhibitor. Twenty- one patients (3%) were addressed to a second allo- SCT, and 243/647 (38%) patients received DLI as part of the salvage ther-apy (Figure S1).The cumulative incidence of post- transplant (pre- relapse) acute GVHD was 24% (n = 210), and this was clinically signif-icant (grade II to IV) in 17% of the cases (n = 141). In parallel, 110 patients (13%) developed chronic GVHD following allo- SCT, before relapse. With a median follow up for survivors of 41.8 months (29.2–65.57), the 1- and 2- year OS of the whole pop-ulation was 55% and 28%, respectively (Figure 1A). The 1- and 2- year RM was 39% and 56%, whereas the 1- and 2- year TRM was 6% and 15%, respectively (Figure 1B). Receiving a treatment for the relapse was associated with a significantly longer OS (at 1 and 2 years: 64% and 34% vs. 25% and 10%; p < 0.001; Figure 1C). By multivariable analysis, the age as a continuous variable (HR 1.01) was independently associated with impaired OS, whereas relapse occurring at least 12 months after transplant (HR 0.00), disease relapsing with MRD positivity and/or molecular mixed chimerism (HR 0.37), being in CR at allo- SCT (HR 0.59), trans-plant performed after 1 line of therapy (HR 0.82), and post- relapse therapy including DLI (HR 0.62) were significantly associated with an advantage in OS (Table S1). Focusing on RM, by multivariable analysis, the age at transplant as a continuous variable was the only factor independently associated with an increased risk (HR 1.01). On the other hand, relapse occurring at least 12 months from transplant (HR 0.38), disease relapsing with MRD positivity and/or molecular mixed chimerism (HR 0.47), disease in CR at allo- SCT (HR 0.59), and post- relapse ther-apy based on HMA±venetoclax (HR 0.56) were independently associated with reduced risk of RM. Post- relapse therapy includ-ing DLI confirmed its independent prognostic impact on TRM by multivariable analysis (HR 1.45) (Table S2).Interestingly, 86% of the patients in the present series were treated at the time of hematological relapse. This point reflects the historical attitude of clinicians to wait for overt relapse after allo- SCT before giving any treatment. Consequently, the re-sults of this study suffer from a bias selection, including mostly very high- risk patients. Nevertheless, we observe a signifi-cantly improved outcome if the relapse is treated (Figure 1C). Interestingly, 48% of the patients who were treated for disease relapse received HMAs±venetoclax, and only 22% of the treated patients received intensive chemotherapy as part of the salvage therapy (Figure  S1). This is a consequence of the well- known toxic profile associated with the low cure rate of conventional TABLE 1    |    Clinical and transplant characteristics of the 859 AML/MDS patients relapsing after allo- SCT included in the study.n = 859Age at diagnosis (years)Mean (SD)/median (Min, Max) 58.5 (12.1)/61.0 [23.0–80.0]Age at SCT (years)Mean (SD)/median [Min, Max] 52.9 (12.2)/54.7 [18.7–74.8]Diagnosis at SCTAML/MDS 768 (90%)/91 (10%)Disease status at SCTNo- CR/CR 352 (41%)/507 (59%)Lines of therapy before SCT> 1/1 419 (49%)/415 (48%)Missing 25 (3%)Donor typeSibling 242 (28%)MUD/MMUD 416 (48%)Haploidentical 197 (23%)Missing 4 (1%)SCs sourceBM 203 (24%)PBSC 646 (75%)UCB 10 (1%)MAC regimenNo/Yes 248 (29%)/611 (71%)GVHD prophylaxisATG/ATLG 600 (70%)PTCy 188 (22%)aGVHDNo/Yes 508 (59%)/210 (24%)Grade II/IV aGVHD 141 (17%)cGVHDNo 680 (79%)Yes 110 (13%)Extensive cGVHD 69 (8%)Time SCT- relapse (months)Mean (SD)/Median [Q1, Q3] 8.85 (10.1)/5.49 [3.0–11.1]Survivors follow- up time (months)Mean (SD)/Median [Q1, Q3] 47.0 (24.5)/41.8 [29.2–65.57]Abbreviations: aGVHD, acute graft versus host disease; AML, acute myeloid leukemia; ATG, anti thymocytes globulin; ATLG, anti T- lymphocytes globulin; BM, bone marrow; cGVHD, chronic graft versus host disease; CR, complete remission; MAC, myeloablative conditioning; MDS, myelodysplastic syndrome; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; PBSC, peripheral blood stem cells; SC, stem cells; SCT, stem cell transplantation; UCB, umbilical cord- blood. 10968652, 2025, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.70030 by ASST DEGLI SPEDALI CIVILI DI BRESCIA, Wiley Online Library on [11/09/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License1904 American Journal of Hematology, 2025chemotherapy in patients relapsing after allo- SCT. The extremely low rate of second allo- SCT (3%) similarly reflects the reluctance of clinicians to perform such a procedure, frequently associated with high transplant- related mortality, particularly in the pres-ence of active disease, and with such a short median time from transplant to relapse (5.49 months). Moreover, the second trans-plant has become more frequently and easily performed fol-lowing the spread in the world of haploidentical allo- SCT with post- transplant cyclophosphamide, and in Italy, between 2015 and 2021, this latter procedure was starting to become widely ad-opted. The results of the multivariable analysis on OS, RM, and TRM are somehow expected, with the conventional factors inde-pendently associated with better or dismal prognosis (Tables S1 and S2). An interval from transplant to relapse ≥ 12 months was independently associated with both improved OS and reduced RM. Moreover, patients with morphological evidence of dis-ease at relapse (more than 5% of BM blast cells) show a dismal OS and an increase in RM. This strongly suggests the benefit of a pre- emptive approach at the time of MRD positivity and/or molecular mixed chimerism. Similar results were observed in our Italian and French retrospective study on 134 patients [4] and by Zuanelli Brambilla and colleagues on a case series of 148 AML/MDS relapses [5]. Moreover, the favorable impact of DLI in association with post- relapse therapy is the indirect proof of the graft versus leukemia effect, and this is confirmed also in the subset of patients treated with HMAs±venetoclax (data not shown). The benefit of DLI in association with salvage therapy is also highlighted in the multivariable analysis on RM (HR 0.56). Notably, the increased risk of TRM when DLI are used (HR 1.45) does not hamper their benefit on OS and RM (Table S2). Several single- center and registry studies highlighted the efficacy of ad-ministration of DLI following disease relapse after allo- SCT, in particular if these were administered in a pre- emptive setting, and other preliminary data suggest some benefit of prophylactic DLI for high- risk AML [6].The major limit of our study is its retrospective design. As a consequence, many data have been collected following specific queries with possible biases and limiting the availability of more detailed analysis. In the meantime, the multicentric nature of this study and the relatively large number of patients included make the findings quite strong and reliable. These results may be the starting point to design prospective studies including early pre- emptive therapy in the presence of MRD positivity and/or molecular chimerism failure, possibly including new agents (e.g., HMAs±venetoclax) in combination with DLI.Affiliations1Chair of Hematology, University of Brescia, Brescia, Italy | 2Adult Bone Marrow Transplant Unit, Program of Cellular Therapy and Research in Hematology, ASST Spedali Civili di Brescia, Brescia, Italy | 3BMT Unit, AOR Villa Sofia Cervello, Palermo, Italy | 4Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Italy | 5Department of Clinical and Experimental Science, University of Brescia, Brescia, Italy | 6University of Milan, Milan, Italy | 7Hematology and Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato- Oncology and Radiotherapy, Grande Ospedale Metropolitano “Bianchi- Melacrino- Morelli”, Reggio Calabria, Italy | 8UO Ematologia e CTMO, Ospedale Guglielmo da Saliceto, Piacenza, Italy | 9Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Padova University Hospital, Padova, Italy | 10Dipartimento di Ematologia, Presidio Ospedaliero S. Bortolo, Vicenza, Italy | 11SS Trapianto Allogenico Cellule Staminali, AOU Citta' della Salute e della Scienza, Torino, Italy | 12Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Florence, Italy | 13Hematology and FIGURE 1    |    Overall survival (OS) of the series (A; 1- year OS = 55%, 2- year OS = 28%); Cumulative Incidence of RM and TRM (B; 1- year RM = 39%, 2- year RM = 56%; 1- year TRM = 6%, 2- year TRM = 15%); OS of treated versus untreated patients (C; treated: 1- year OS = 64%, 2- year OS = 34%; Untreated: 1- year OS = 25%, 2- year OS = 10%). 10968652, 2025, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.70030 by ASST DEGLI SPEDALI CIVILI DI BRESCIA, Wiley Online Library on [11/09/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License1905Transplant Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy | 14Ematologia e Centro Trapianti di Midollo, Comprensorio di Bolzano, Azienda Ospedaliera Alto Adige, Bolzano, Italy | 15Department of Onco Hematology, UOC Stem Cell Transplant, Fondazione Policlinico Tor Vergata, Rome, Italy | 16Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy | 17Unità Operativa di Ematologia con TMO, A.O.R. S. Carlo, Potenza, Italy | 18Struttura Complessa Ematologia, Unità Trapianti di Midollo, AOU Policlinico di Modena, Italy | 19Department of Clinical and Biological Sciences, University of Turin, Turin, Italy | 20Internal Medicine and Haematology Division, San Luigi University Hospital, Turin, Italy | 21UOC Hematology and Transplant, Vito Fazzi, Lecce, Italy | 22UOC di Ematologia e Terapia Cellulare, Ospedale C e G Mazzoni, Ascoli Piceno, Italy | 23UOC Ematologia, AOU Policlinico Umberto I, Sapienza University of Rome, Rome, Italy | 24Azienda Ospedaliero Universitaria delle Marche, Ancona, Italy | 25Haematology Unit, San Gerardo Hospital, Monza, Italy | 26Hematologic Clinic and Transplant Center, University Hospital of Central Friuli, DMED, University of Udine, Udine, Italy | 27Department of Hematology and Bone Marrow Transplantation, “Card. G. Panico” Hospital, Tricase, Italy | 28Stem Cell Transplant Program AORN Cardarelli, Naples, Italy and Biomedicine and Prevention Department of Tor Vergata University, Rome, Italy | 29SC Ematologia e CTMO”, Ospedale Businco, ARNAS Brotzu, Cagliari, Italy | 30Unit of Bone Marrow Transplantation – Division of Hematology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy | 31Hematology and BMT Unit, AOU of Parma, Parma, Italy | 32BMT Unit. ASST Papa Giovanni XXIII, Bergamo, Italy | 33Clinica Ematologica, Universita' di Catania, Catania, Italy | 34Hematology and Transplant Unit, AOU San Giovanni di Dio e Ruggi d'Aragona, Department of Medicine and Surgery, University of Salerno, Fisciano, Italy | 35UOC Ematologia Ospedale dell'Angelo Venezia Mestre, Venezia Mestre, Italy | 36Ematologia con Trapianto, Ospedale A. Perrino, Brindisi, Italy | 37Department of Medicine, Hematology and Bone Marrow Transplant Unit, Verona University, Verona, Italy | 38GITMO Trial Office, Geno, ItalyEthics StatementAll patients included in the registry provided informed consent for data registration in the PROMISE database. The study was conducted in compliance with current national and European legislation on clinical trials and in accordance with the Declaration of Helsinki and the prin-ciples of good clinical practice.Conflicts of InterestThe authors declare no conflicts of interest.Data Availability StatementThe data that support the findings of this study are available from the corresponding author upon reasonable request.References1. F. Kreidieh, I. Abou Dalle, N. Moukalled, et  al., “Relapse After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: An Overview of Prevention and Treatment,” International Journal of Hematology 116, no. 3 (2022): 330–340, https:// doi. org/ 10. 1007/ s1218 5- 022- 03416 - 7.2. M. Gooptu, H. M. Murdock, and R. J. Soiffer, “How I Treat AML Relapse After Allogeneic HCT,” Blood 24 (2024): 2024025705, https:// doi. org/ 10. 1182/ blood. 20240 25705 .3. A. Latouche, R. Porcher, and S. Chevret, “A Note on Including Time- Dependent Covariate in Regression Model for Competing Risks Data,” Biometrical Journal 47 (2005): 807–814.4. E. Accorsi Buttini, C. Doran, M. Malagola, et al., “Donor Lymphocyte Infusion in the Treatment of Post- Transplant Relapse of Acute Myeloid Leukemias and Myelodysplastic Syndromes Significantly Improves Overall Survival: A French- Italian Experience of 134 Patients,” Cancers 16, no. 7 (2024): 1278, https:// doi. org/ 10. 3390/ cance rs160 71278 .5. C. Zuanelli Brambilla, S. M. Lobaugh, J. D. Ruiz, et al., “Relapse After Allogeneic Stem Cell Transplantation of Acute Myelogenous Leukemia and Myelodysplastic Syndrome and the Importance of Second Cellular Therapy,” Transplant Cell Therapy 27, no. 9 (2021): 771.e1–771.e10, https:// doi. org/ 10. 1016/j. jtct. 2021. 05. 011.6. F. Patriarca, A. Sperotto, F. Lorentino, et  al., “Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO),” Frontiers in Oncology 15, no. 10 (2020): 572918, https:// doi. org/ 10. 3389/ fonc. 2020. 572918.Supporting InformationAdditional supporting information can be found online in the Supporting Information section. Table S1: Univariable and Multivariable analysis on Overall Survival. Table  S2: Univariable and Multivariable analy-sis on Relapse Mortality and Treatment- Related Mortality. Figure S1: Flow chart of the post- relapse treatment of our series.  10968652, 2025, 10, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ajh.70030 by ASST DEGLI SPEDALI CIVILI DI BRESCIA, Wiley Online Library on [11/09/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

English

Outcome of Patients With Acute Myeloid Leukemias or Myelodysplastic Syndromes After Relapsing From Allogeneic Stem Cell Transplantation: The GITMO AML/MDS-Relapse Registry Study

Rubiola, Andrea

Camera, Stefano

Fornengo, Nicolao

Wiener filtering and multi-tracer techniques for dark matter
  cross-correlations between gamma-ray emission and galaxy catalogs

Ribaldone, D. G.

IBD impact on quality of life and perception of disease activity in Italian patients and physicians: An IBD-PODCAST study sub analysis

Santus, Daniela

Leggere gli spaziPercezione narrativa di Eretz Israel Matteo Bona e Daniela SantusLeggere gli spaziMatteo Bona e Daniela SantusPrefazione di Leonardo MercatantiCollana coordinata e diretta da Leonardo Mercatanti e Gaetano Sabato“Geografia, culture e società”€ 19,00Saper leggere gli spazi rappresenta una delle pratiche più importanti per la disciplina geografica. Si tratta di una competenza caratterizzante, da intendersi anche come reale opportunità di ricerca. Sia chiaro: la lettura degli spazi non è una scelta di campo politico, come molti sono propensi a pensare quando il tema trattato è Israele, ma è una abilità che rimanda alla sensibilità e alla percezione soggettiva dei geografi, o comunque dei viaggiatori di ogni tempo, che offrono il loro sguardo al territorio cercando elementi che sappiano raccontarlo in modo convincente e utile al progresso degli studi, e contribuiscano soprattutto a definire quel senso del luogo inteso come surplus umano al divenire del paesaggio. La lettura di questo volume, ricco di informazioni e di curiosità, fa emergere la complessità di un territorio davvero unico sotto il profilo culturale e identitario. Per questo si ritiene possa essere di sicuro impatto sui destinatari: dagli studiosi appassionati ai curiosi di conoscere in modo diverso Israele. La sequenza dei capitoli delinea inoltre un percorso didattico perfettamente coerente con gli obiettivi di un corso universitario di scienze umane e culturali [dalla prefazione di Leonardo Mercatanti].Gli Autori:Matteo Bona: studioso di ecocritica, environmental e digital humanities . Ha al suo attivo diverse pubblicazioni e articoli scientifici tra cui I luoghi e le frontiere dell’essere (Il Sileno, 2023), “Comprehending the risk throughout a literary-geocritical approach. Rushdie’s The Satanic Verses as evidence and an opportunity in investigating risk scenarios” (AIMS Geosciences , 2024); “Verbal Semantics and memory in Shaping Narrative Space: Identity and Recollection in My Name is Asher Lev ” (Literature, Geography and the Poetics of Space, Il Sileno, 2024); ”Media narratives and the social perception of violence: a computational approach to trauma dynamics” (Società e Diritti, UniMi, 2025).Daniela Santus: docente di Geografia presso il Dipartimento di Lingue e Letterature Straniere e Culture Moderne dell’Università di Torino si occupa di geografia culturale, geografia della religione e geopolitica. Tra i suoi ultimi lavori Frammenti di paesaggio: geografia, t u rismo e sostenibilità in Germania (con E. Pugliese, Il Sileno, 2024); Il Corano e le donne (con S. Ansaloni, Nuova Trauben, 2022); HaTikva . Spazio e percezione nel Tanakh e in Eretz Israel (con L. Beltramo, Nuova Trauben, 2021).Percezione narrativa di Eretz IsraelLibro Leggere gli spazi def.indd   2-4 27/05/25   17:32

Italian

Leggere gli spazi. Percezione narrativa di Eretz Israel

Leone, Massimo

Les normes assiégées

Calavita, Oscar

Criptofonini e Ordine Europeo di Indagine Penale (OEI): ancora zone d'ombra

Sgroi, Mauro

Hydrogen chemisorption capability of reduced graphene oxide membranes

Crocco, Edoardo

Stakeholders’ Expectations and Actual Disclosure: A Big Data analysis of Sustainability Reporting in Higher Education

Terlizzi, Giulia

LA PLURALITÀ DEL CONSENSO NEGLI ACCORDI DI MATERNITÀ SURROGATA

Costantini, Anna

Commento all'art. 209 c.p.: Persona giudicata per più fatti

University of Turin

Not a member yet