Francesca Pavesi

@asst-valleolona.it

Hematology and Stem Cell Transplantation Division - Oncology Department
ASST Valle Olona - Ospedale di Busto Arsizio

Francesca Pavesi


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RESEARCH, TEACHING, or OTHER INTERESTS

Hematology, Biochemistry, Genetics and Molecular Biology
11

Scopus Publications

Scopus Publications

  • Venetoclax plus hypomethylating agents as effective bridge therapy to allogeneic stem cell transplant in relapsed/refractory acute myeloid leukaemia: A subanalysis of the AVALON study
    Elisabetta Petracci, Francesca Pavesi, Luca Castagna, Patrizia Zappasodi, Cristina Papayannidis, Calogero Vetro, Vincenzo Federico, Alessandro Cignetti, Erika Borlenghi, Nicola Fracchiolla, Luca Facchini, Luca Maurillo, Ernesta Audisio, Massimo Bernardi, Felicetto Ferrara, Francesco Lanza, Carmine Selleri, Ilenia Manfra, Claudio Cerchione, Jacopo Nanni, Andrea Davide Romagnoli, Giovanni Marconi, Chiara Zingaretti, Ivana Lotesoriere, Federica Gigli, Giovanni Martinelli, Elisabetta Todisco
    British Journal of Haematology, 2026
    Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for patients with relapsed or refractory (REF/REL) acute myeloid leukaemia (AML). However, many patients—particularly older or unfit individuals—are unable to reach transplant due to poor responses to salvage chemotherapy or toxicities. In recent years, the combination of hypomethylating agents (HMAs) with venetoclax (VEN) has demonstrated robust activity and manageable toxicity in both newly diagnosed (ND) and REF/REL AML.1, 2 In this context, we conducted a subanalysis of the AVALON, a retrospective Italian cohort evaluating real-world outcomes of HMA-VEN in AML, to investigate the feasibility and outcomes of HMA-VEN as a bridging therapy to allo-HSCT in the REF/REL setting. AVALON included 147 patients with REF/REL AML treated with HMA-VEN between 1 January 2015 and 1 April 2020, across 32 haematology centres.3 Twenty patients who received allo-HSCT prior to initiating HMA-VEN were excluded. Of the 127 remaining patients, 36 (28.3%) underwent allo-HSCT following HMA-VEN therapy. Transplanted patients were younger, fitter, more likely to have de novo or refractory AML, and to combine with decitabine compared to non-transplanted patients. Among the transplant cohort, 72.2% achieved a composite complete remission (cCR), including complete remission (CR), CR with incomplete haematological recovery (CRi) or morphologic leukaemia-free state (MLFS), prior to transplant (Table 1; Table S1). The median time from HMA-VEN initiation to allo-HSCT was 3.8 months [IQ–IIIQ: 2.5–5.3]. Sixteen patients (44.4%) received haploidentical transplants, and 28 (77.8%) underwent myeloablative conditioning (MAC). In the entire REF/REL cohort (n = 127), consolidation with allo-HSCT following HMA-VEN was associated with significantly longer overall survival (OS) and event-free survival (EFS). The hazard ratio (HR) for OS was 0.53 (95% confidence interval [CI]: 0.28–0.98; p = 0.045). When limiting the analysis to those who achieved cCR (n = 49), outcomes were even more favourable (HR for OS: 0.30, 95% CI: 0.11–0.84; p = 0.021). Overlapping results were obtained for EFS. Analyses used a Cox model with allo-HSCT as a time-dependent covariate, adjusting for age, fitness and European LeukemiaNet risk. In the allo-HSCT group (n = 36), median OS and EFS were 12.9 months (95% CI: 5.46–32.63) and 11.8 months (95% CI: 5.10–32.63), respectively, with a median follow-up of 20.3 months (Figure 1). In univariate analysis using the Cox model, the main factors associated with OS and EFS were disease status at treatment initiation and type of the conditioning regimen (Figure S1). Borderline associations were also observed with pretransplant response status and AML type (for OS only) (Figure S2). The 1-year cumulative incidence of relapse (CIR) post-transplant was 18.4% (95% CI: 7.2%–33.6%) in the overall transplanted population, while 22.1% (95% CI: 7.5%–41.5%) among patients transplanted in remission. One-year non-relapse mortality (NRM) was 34.2% (95% CI: 19.0%–50.1%), decreasing to 24.2% (95% CI: 9.5%–42.6%) in those transplanted in cCR. The 6-month cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) was 16.7% (95% CI: 6.6%–30.6%), with grade III–IV aGVHD in 13.9% of patients. The incidence of chronic GVHD was 8.3% (95% CI: 1.4%–24.0%) at 1 year and increased to 14.0% (95% CI: 3.2%–33.0%) at 2 years, with moderate-to-severe forms remaining uncommon (4.5% and 11.0% respectively). One-year GVHD-free, relapse-free survival (GRFS) was 44.4%, with a median GRFS of 10.0 months (Figure S3). Among transplanted patients, 14 of 36 (38.9%) were alive and disease-free at last follow-up. The most common causes of death were relapse (n = 9), GVHD (n = 5) and infections (n = 4). Our study provides further evidence supporting the feasibility and effectiveness of HMA-VEN as a bridge to allo-HSCT in patients with REF/REL AML. In this real-world Italian cohort, about a quarter of the REF/REL AML patients treated with HMA-VEN were able to proceed to allo-HSCT, with promising post-transplant outcomes in terms of remission, survival and manageable toxicity. Our results show that 72.2% of patients undergoing allo-HSCT after HMA-VEN achieved CR or CRi prior to transplant, consistent with previous studies reporting high CR/CRi rates in the REF/REL setting with VEN-based regimens.1, 2 The median time from HMA-VEN initiation to transplant was 3.8 months, underscoring the regimen's ability to achieve timely disease control, a critical factor for successful transplantation. This short time interval may also reflect that 44% of patients received a transplant from a haplo-identical donor, which may be arranged more rapidly than matched unrelated donors' allo-HSCT. Several studies have reported outcomes of VEN-HMA used as a bridge to allo-HSCT, but few have focused on REF/REL AML patients,4-6 often grouping them with ND patients. This makes it challenging to assess post-HSCT outcomes for the REF/REL subgroup. Sandhu et al. analysed 19 ND and 13 REF/REL AML patients (median age 62 years) and found CR/CRi rates after Venetoclax plus azacitidine (VEN-AZA) of 68.8% for ND-AML and 31.3% for REF/REL AML. Post allo-HSCT, their cohort showed a 1-year OS of 62.5%, relapse-free survival (RFS) of 43.8%, CIR of 37.5% and NRM of 18.8%.4 Kennedy et al. studied 46 ND and 42 REF/REL AML patients (including 5 s transplants), with a median age of 67 years. They reported 1-year OS, CIR and NRM rates of 78%, 36% and 17% respectively.5 Bang et al. evaluated post-allo-HSCT outcomes in 10 ND and 40 REF/REL AML patients treated with VEN-HMA therapy, with a median age of 53 years at transplant. The proportions achieving CR/CRi or MLFS were 90% for ND and 92.5% for REF/REL AML. After a median follow-up of 13.7 months, 1-year OS, RFS, CIR and NRM probabilities were 63.7%, 59.3%, 28.5% and 12.2% respectively. In our study, the median age at transplant was 56 years, and 72.2% of patients achieved a response to VEN-HMA prior to allo-HSCT. Post-transplant, 1-year OS, EFS, CIR and NRM were 53.4%, 47.4%, 18% and 34.2% respectively. Our findings indicate that consolidation with allo-HSCT following HMA-VEN therapy significantly prolonged OS in both the overall REF/REL cohort and particularly in patients achieving CR/CRi. EFS was consistent with OS data, as expected in this population and reported in other studies.4-6 In univariate analysis, we observed a significant benefit for patients receiving MAC conditioning compared to those who received Reduced intensity conditioning (RIC). Another factor associated with OS and EFS was disease status at treatment initiation. Compared to other studies,4, 5 our transplant cohort had a younger median age, and 90% of the population was fit, which may explain why 78% had an MAC and nearly half of the population had a transplant from a haploidentical donor. The finding that the majority of patients in this cohort were treated with haploidentical allo-HSCT and received high-intensity conditioning regimens further supports the idea that HMA-VEN can enable the successful use of allo-HSCT in patients who might otherwise not be candidates for transplantation due to insufficient remission or high disease burden (especially refractory diseases). Compared to other studies,4-6 our NRM rate is somewhat higher, likely reflecting differences in patients' characteristics and the small sample size of our REF/REL cohort. However, in patients transplanted in CR/CRi, the NRM decreased to 24.2%, suggesting that disease control before transplant is a critical factor in minimizing transplant-related toxicity. The majority of NRM events were due to infections and GVHD, which remain leading challenges post-allo-HSCT. Interestingly, the cumulative incidence of grade II–IV aGVHD was relatively low (16.7% at 6 months), and chronic GVHD occurred in only 8.3% at 1 year, suggesting that pretreatment with HMA-VEN may not exacerbate GVHD risk and could offer an immunologically favourable profile, possibly due to limited toxicity and myelosuppression-focused action. Our study also revealed a low relapse incidence (18.4% at 1 year), particularly in those transplanted in remission (22.1%), highlighting that HMA-VEN may not compromise post-transplant disease control. This compares favourably with prior reports where relapse rates often exceed 30% after allo-HSCT in REF/REL AML.4-6 Moreover, the GRFS of 44.4% at 1 year provides a meaningful measure of quality-adjusted survival in this patient population. A strength of our analysis lies in its real-world setting, capturing outcomes across multiple centres and reflecting different transplant practices. However, there are several limitations. First, the retrospective design and inherent selection bias may limit the generalizability of our findings. Patients selected for transplant were younger and fitter, with a predominance of de novo AML and refractory rather than relapsed disease. Second, time to response and disease status assessments were not standardized, relying on investigator judgement Third, the cohort size, while one of the largest real-life European series to date, remains modest, and longer follow-up is needed to better define the durability of responses and late toxicity. In conclusion, despite the high NRM, our data confirm the utility of HMA-VEN as an effective bridge to allo-HSCT in REF/REL AML, because it brings an advantage in terms of relapse, especially considering that approximately 30% of patients in our cohort were not in CR/CRi at the time of allo-HSCT. Furthermore, 38.9% of patients alive and disease-free at last follow-up have an expected good quality of life, as demonstrated by the GRFS of 44%. These findings support the broader implementation of HMA-VEN in this setting, especially for patients traditionally considered ineligible for intensive salvage therapy. Future trials comparing HMA-VEN to intensive chemotherapy as a pretransplant regimen, and studies incorporating matched related donor monitoring and maintenance strategies post-transplant are warranted to further optimize outcomes in this high-risk group. E.T., E.P., L.C., F.P. and G.Mart. conceived the analysis and contributed to the definition of methods and end-points. E.P. performed statistical analysis. C.Z. and I.L. were involved in study database creation and revision. P.Z., C.P., C.V., V.F., A.C., E.B., N.F., L.F., L.M., E.A., M.B., F.F., F.L., C.S., I.M., C.C., J.N., A.D.R., G.Marc., F.G., G.Mart. and E.T. enrolled patients in the study. All the authors contributed in writing and reviewing the manuscript. This work was supported thanks to the contribution of Ricerca Corrente by the Italian Ministry of Health. The authors declare no conflicts of interest. The AVALON study (CT.gov: NCT04070807) was approved by the Romagna Ethics Committee on 10 April 2019 (Prot. 3371/2019) and subsequently by the ethics committee of each participating institution. It was also conducted in accordance with the ethical standards in the 1964 Declaration of Helsinki. All patients provided informed consent. In this work, generative artificial intelligence (AI) has not been used. Questions regarding data sharing should be addressed to the corresponding author; data will be shared upon request. Figure S1. Kaplan–Meier curves for overall survival (top panels) and event-free survival (bottom panels), by disease status (left) and conditioning regimen (right). Figure S2. Kaplan–Meier curves for overall survival (top panels) and event-free survival (bottom panels), by response status (left) and type of acute myeloid leukaemia (right). Figure S3. Kaplan–Meier curve for graft-versus-host disease (GVHD)-free, relapse-free survival (events: acute GVHD grade III–IV, systemic therapy-requiring chronic GVHD, relapse or death from any cause in the first post-HCT year). Table S1. Patient characteristics of relapsed or refractory acute myeloid leukaemia patients treated with hypomethylating agent-venetoclax receiving allo-haematopoietic stem cell transplantation, overall and by disease status before transplant. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
  • Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia
    Matteo Maria Naldini, Gabriele Casirati, Matteo Barcella, Paola Maria Vittoria Rancoita, Andrea Cosentino, Carolina Caserta, Francesca Pavesi, Erika Zonari, Giacomo Desantis, Diego Gilioli, Matteo Giovanni Carrabba, Luca Vago, Massimo Bernardi, Raffaella Di Micco, Clelia Di Serio, Ivan Merelli, Monica Volpin, Eugenio Montini, Fabio Ciceri, Bernhard Gentner
    Nature Communications, 2023
    Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts.
  • miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease
    Carolina Caserta, Silvia Nucera, Matteo Barcella, Grazia Fazio, Matteo Maria Naldini, Riccardo Pagani, Francesca Pavesi, Giacomo Desantis, Erika Zonari, Mariella D’Angiò, Paola Capasso, Angelo Lombardo, Ivan Merelli, Orietta Spinelli, Alessandro Rambaldi, Fabio Ciceri, Daniela Silvestri, Maria Grazia Valsecchi, Andrea Biondi, Giovanni Cazzaniga, Bernhard Gentner
    Leukemia, 2023
  • Second Solid Cancers After Hematopoietic Stem Cell Transplantation: Active Surveillance During Long-term Follow-up
    Maria Teresa Lupo-Stanghellini, Simona Piemontese, Andrea Assanelli, Fabio Serpenti, Sara Mastaglio, Daniela Clerici, Fabio Giglio, Raffaella Greco, Francesca Lorentino, Francesca Pavesi, Francesca Farina, Sarah Marktel, Consuelo Corti, Jacopo Peccatori, Fabio Ciceri
    Hemasphere, 2021
    Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as a curative option in the treatment of malignant and nonmalignant diseases. Eighty percent of those who survive the first 2 years are expected to become long-term survivors. However, the prevalence of chronic-health conditions approaches 75% among HSCT survivors. Second solid cancers (SSCs) are the most clinically relevant late effects: cumulative incidence increases steadily between 2% and 6% at 20 years and is substantially higher when compared to general population.1–3 Among risk factors radiation, graft versus host disease (GvHD), immunosuppression related to GvHD and association with viral infection (such as hepatitis C virus and human papillomavirus) increased risk for SSCs after HSCT.4 Recently, an EBMT cohort study evaluated the outcome of patients with a SSC after HSCT. Among 1443 patients with 18 different SSCs, 5-year overall survival (OS) was only 47%.5 Our study seeks to evaluate the utility of an intensive screening and counseling planned follow-up for SSCs after HSCT to pursue early detection and intervention. An all-comprehensive standardized life-time follow-up of HSCT survivors is applied at our Center, according to Jacie Standards and international guidelines.6,7 Health promotion, SSCs counseling and screening are part of this follow-up. In addition to blood tests, SSCs screening included yearly abdominal ultrasound, ophthalmologist, ENT, dermatological, and dental consultation, in addition to gynecological consultation, mammography and PAP test for female patients (Supplemental Digital Table 1; https://links.lww.com/HS/A203). This is a prospective cohort analysis of data collected at our long-term follow-up clinic between 2011 and 2019 including 442 adult patients—with at least 24 months follow-up—transplanted between 1996 and 2017. A written consent was given by patients allowing the use of medical records for research in accordance with the Declaration of Helsinki. Primary endpoints were incidence of SSC, incidence of death from SSC, and OS following a diagnosis of SSC. Cumulative incidence functions were used to estimate the incidence of both SSCs and death from SSCs. Death without SSCs and any death not due to SSCs, such as death from primary disease and transplant-related death, were competing events for incidence of SSCs and death from SSCs, respectively.8 OS from transplant was calculated from the day of HSCT until death or the last follow-up. Survival following SSC diagnosis was calculated from the time of SSC diagnosis to death from any causes. The probability of OS and of survival after SSC was estimated using the Kaplan–Meier method. All tests were two-sided. Statistical analyses were performed with SPSS 20 (SPSS Inc./IBM, Armonk, NY). Patients features including patients underlying disease and donor type are reported in Table 1. Median follow-up was 78 months (range 24–326 mo). At last evaluation, 360 patients were alive and the 5-year OS was 85% ± 2% (Fig. 1A) in the entire population. Table 1 - Characteristics of Patients All Patients SSCs Patients N 442 81 Sex (M/F) 276/166 32/16 Age (at HSCT/at SCCs/at last FU) 49/n.a./56 58/61/64 Primary disease Acute leukemia 246 45 Hodgkin disease 34 2 Non-Hodgkin disease 51 13 Myeloma 25 4 Myelodysplasia 55 11 Others 31 6 Donor type MRD 129 22 MUD 141 28 CB 8 1 MMRD 164 30 Acute GvHD history 171 29 Chronic GvHD history 214 36 SSCs diagnosis Favorablea Thyroid 1 Cervix 10 Prostate 4 Breast 3 Melanoma 2 NMSC 43 Intermediatea Kidney 3 Oropharyngeal 1 Bladder 2 Ovarian 0 Sarcomas 0 Colorectal 1 Endometrial 1 Poora Gastric 1 Brain 0 Esophageal 0 Hepatobiliary 0 Lung 9 Pancreas 2 Donor leukemia 2 aClassification adapted from Tichelli et al.5CB = cord blood; FU = follow-up; GvHD = graft versus host disease; HSCT = hematopoietic stem cell transplantation; MMRD = mismatch-related donor; MRD = match-related donor; MUD = match-unrelated donor; NMSC = nonmelanoma skin cancer; SSCs = second solid cancers. Figure 1.: Overall survival analysis. (A) Overall survival for entire cohort of patients; (B) cumulative incidence of second solid cancer; (C) overall survival from diagnosis of second solid cancer.Eighty-five SSCs occurred in 81 patients during time of observation (Table 1). Five- and 10-year SSCs cumulative incidence was 15% ± 2% and 27% ± 3% (Fig. 1B), median time to diagnosis was 39 months (range 2–243 mo). When considering outcomes after cancer events, median follow-up after diagnosis of SSCs was 56 months (range 1–190 mo). Five- and 10-year OS following occurrence of SSCs was 78% ± 5% and 54% ± 1% (Fig. 1C). In multivariate analysis, the only risk factor for a higher incidence of SSCs was age at transplant >60 years (Table 2). The other covariates used in the cox model were as follows: patient sex, TBI, presence of metabolic syndrome, type of donor, and previous occurrence of chronic GvHD moderate/severe as a T-dependent covariate. SSCs were referred to the appropriate oncology specialists and treated according to standard practice. The cumulative incidence of mortality for SSCs was 1% at 5 years and 4% ± 2% at 10 years. Table 2 - Multivariate Analysis of the Association Between Patients/Transplant Characteristics and SCC Second Solid Cancer HR (95% CI) P Patient age >60 vs <60 y 3.1 (1.467–6.884) 0.003 TBI 1.6 (0.731–3.510) 0.239 Moderate/severe chGvHD 1 (1–1) 0.236 CI = confidence interval; HR = hazard ratio GvHD = graft versus host disease; SSCs = second solid cancers. HSCT survivors are at a defined risk of developing SSCs. The pathogenesis of SSCs is multifactorial: interaction between cytotoxic treatment, genetic predisposition, environmental factors, viral infections, GVHD, and its immunosuppression may play a role.7 Compared with general population, HSCT recipients are 3.6 times more likely to die of SSCs.2,3 Our 5-year cumulative incidence of SSCs was 15%: this is higher than the previously reported registry studies.1–6 Possible explanations for this difference are the changes occurred in the field of HSCT such as the use of more oncogenic drugs (ie, voriconazole as antifungal prophylaxis), the older patient population, or the higher sensitivity offered by a dedicated intensive follow-up program including proactive oncologic screening. In this regard, a recent CIBMTR/EBMT working group’s guidelines for SSCs outlined how incidence of SSCs based on registry data may underestimate the true incidence.7 Notably, the observed cancer cases in our cohort outnumber the expected in the general population matched for age and sex (Supplemental Digital Figure 1 and Supplemental Digital Table 2; https://links.lww.com/HS/A203)9—confirming the results summarized from existing literatures by Inamoto et al.7 Our prospective experience of intensive oncology screening suggests that the real-life incidence of SSCs is high, especially in patients transplanted after their 60s. Earlier detection of SSCs may result in better survival (Fig. 1C), unveiling the importance of dedicated surveillance program to enhance diagnosis, treatment, and overall outcome. Disclosures 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.
  • Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience
    Elisabetta Xue, Francesca Lorentino, Francesca Pavesi, Andrea Assanelli, Jacopo Peccatori, Massimo Bernardi, Consuelo Corti, Fabio Ciceri, Maria Teresa Lupo Stanghellini
    Leukemia Research, 2021
  • Posttransplantation Cyclophosphamide- and Sirolimus-Based Graft-Versus-Host-Disease Prophylaxis in Allogeneic Stem Cell Transplant
    Raffaella Greco, Francesca Lorentino, Serena Albanese, Maria Teresa Lupo Stanghellini, Fabio Giglio, Simona Piemontese, Daniela Clerici, Lorenzo Lazzari, Magda Marcatti, Sara Mastaglio, Elisabetta Xue, Francesca Farina, Francesca Pavesi, Andrea Assanelli, Matteo G. Carrabba, Sarah Marktel, Luca Vago, Chiara Bonini, Consuelo Corti, Massimo Bernardi, Fabio Ciceri, Jacopo Peccatori
    Transplantation and Cellular Therapy, 2021
    Post-transplantation cyclophosphamide (PTCy) has emerged as a promising graft-versus-host-disease (GVHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical donors and more recently in matched donor transplants. Herein, we describe our real-life experience on 249 adult patients undergoing allogeneic HSCT, from HLA-matched related (MRD), HLA-matched unrelated (MUD), or mismatched related donors (MMRD). Patients received unmanipulated peripheral blood stem cells (PBSCs), using a GVHD prophylaxis with PTCy and sirolimus. Mycophenolate mofetil was added in MUD or MMRD. In the HLA-matched donor group (MRD, n = 48, MUD, n = 50), the cumulative incidence of grades II-IV and III-IV acute GvHD was 23% and 9% at 100 days, respectively. The cumulative incidence of chronic GvHD was 25% at 2 years, severe only for 5% of the patients. The cumulative incidences of relapse and transplant-related mortality (TRM) were 31% and 9% at 2 years, respectively. The 2-year overall survival (OS) was 72% and progression-free survival (PFS) 60%; the composite endpoint of GvHD/relapse-free survival (GRFS) was 52% at 2 years. In the haploidentical donor group (n = 151), we documented a cumulative incidence of grades II-IV and III-IV acute GVHD of 35% and 20% at 100 days, respectively, and a cumulative incidence of chronic GvHD of 39% at 2 years. We observed severe chronic GVHD in 15% of the patients. The cumulative incidence of relapse and TRM was 32% and 25% at 2 years, respectively. The 2-year OS was 48%, whereas PFS was 43%; GRFS was 28% at 2 years. However, more patients in the haploidentical group presented high/very high disease risk index (DRI) and higher HCT-comorbidity index. In patients classified in the low-intermediate DRI, 2-year GRFS was 53% in MRD, 65% in MUD, and 46% in haploidentical HSCT (P = .33). Sirolimus-PTCy platform deserves further investigation as an alternative to calcineurin-inhibitor-based GVHD prophylaxis for all donor sources. In patients presenting a low-intermediate DRI, this strategy translates in relevant survival independently from the transplant source.
  • The place of ceftazidime/avibactam and ceftolozane/tazobactam for therapy of haematological patients with febrile neutropenia
    Daniela Clerici, Chiara Oltolini, Raffaella Greco, Marco Ripa, Fabio Giglio, Sara Mastaglio, Francesca Lorentino, Francesca Pavesi, Francesca Farina, Carmine Liberatore, Barbara Castiglion, Chiara Tassan Din, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Paolo Scarpellini, Fabio Ciceri, Antonella Castagna
    International Journal of Antimicrobial Agents, 2021
  • CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program
    Fabio Guolo, Luana Fianchi, Paola Minetto, Marino Clavio, Michele Gottardi, Sara Galimberti, Giuliana Rizzuto, Michela Rondoni, Giambattista Bertani, Michela Dargenio, Atto Bilio, Barbara Scappini, Patrizia Zappasodi, Anna Maria Scattolin, Francesco Grimaldi, Giuseppe Pietrantuono, Pellegrino Musto, Marco Cerrano, Stefano D’Ardia, Ernesta Audisio, Alessandro Cignetti, Crescenza Pasciolla, Francesca Pavesi, Anna Candoni, Carmela Gurreri, Monica Morselli, Caterina Alati, Nicola Fracchiolla, Giovanni Rossi, Manuela Caizzi, Fabrizio Carnevale-Schianca, Agostino Tafuri, Giuseppe Rossi, Felicetto Ferrara, Livio Pagano, Roberto Massimo Lemoli
    Blood Cancer Journal, 2020
    Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.
  • SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub
    Rocco Piazza, Vera Magistroni, Sara Redaelli, Mario Mauri, Luca Massimino, Alessandro Sessa, Marco Peronaci, Maciej Lalowski, Rabah Soliymani, Caterina Mezzatesta, Alessandra Pirola, Federica Banfi, Alicia Rubio, Delphine Rea, Fabio Stagno, Emilio Usala, Bruno Martino, Leonardo Campiotti, Michele Merli, Francesco Passamonti, Francesco Onida, Alessandro Morotti, Francesca Pavesi, Marco Bregni, Vania Broccoli, Marc Baumann, Carlo Gambacorti-Passerini
    Nature Communications, 2018
    SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel–Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations. Gene ontology analysis of deregulated SETBP1 target genes indicates that they are also key controllers of visceral organ development and brain morphogenesis. In line with these findings, in utero brain electroporation of mutated SETBP1 causes impairment of mouse neurogenesis with a profound delay in neuronal migration. In summary, this work unveils a SETBP1 function that directly affects gene transcription and clarifies the mechanism operating in myeloid malignancies and in the Schinzel–Giedion syndrome caused by SETBP1 mutations.
  • Emerging resistant bacteria strains in bloodstream infections of acute leukaemia patients: results of a prospective study by the Rete Ematologica Lombarda (Rel)
    Chiara Cattaneo, P. Zappasodi, V. Mancini, C. Annaloro, F. Pavesi, C. Skert, A. Ferrario, E. Todisco, V. Saccà, L. Verga, A. Passi, M. Da Vià, S. Ferrari, G. Mometto, M. Petullà, A. Nosari, G. Rossi
    Annals of Hematology, 2016
  • Elderly patients > 65 years of age with acute myeloid leukemia and normal karyotype benefit from intensive therapeutic programs
    Massimo Bernardi, Matteo Carrabba, Carlo Messina, Raffaella Milani, Elisa Sala, Francesca Pavesi, Bernhard Gentner, Jacopo Peccatori, Andrea Assanelli, Sarah Marktel, Consuelo Corti, Alessandra Forcina, Luca Vago, Fabio Ciceri
    American Journal of Hematology, 2016