UOSD HAEMATOLOGY AND STEM CELL TRANSPLANTATION
Head: Andrea Mengarelli, MD
STAFF
- Svitlana Gumenyuk
- Francesco Marchesi
- Francesca Palombi
- Francesco Pisani
- Daniela Renzi
- Atelda Romano
- Antonio Spadea
- Caterina Viggiani
- Ambra Albertini
- Anna Attico
- Giuseppina Cafarella
- Roberta Capobianco
- Silvia Di Fraia
- Katia Di Prospero
- Graziella De Luca
- Gianluca Falzone
- Federica Izzo
- Andrea Longo
- Marco Prete
- Anna Petrucci
- Fabrizio Pochettino
- Romina Riccio
- Simona Sgromo
- Raffaele Speranza
- Chiara Falcicchio
The effort of Hematology and Transplant Unit was aimed at carrying out clinical trials of primary relevance in different hematological malignancies working in cooperation with other hematological institutions. In particular, our Unit is a member of the following cooperative group:
- Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA)
- European Organisation for Research and Treatment of Cancer (EORTC)
- Fondazione Italiana Linfomi (FIL)
- International Extranodal Lymphoma Study Group (IELSG)
- Gruppo Romano Mielodisplasie (GROM)
- Gruppo Laziale Sindromi Mieloproliferative Croniche Ph1 neg.
- Sorveglianza Epidemiologica Infezioni Fungine in Emopatie Maligne (SEIFEM)
- Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON)
- Gruppo Italiano Trapianto Midollo Osseo (GITMO).
Circulating and tissue microRNAs in Diffuse Large B-Cell Lymphoma (DLBCL): preliminary data suggest that high expression level of serum miR-22 in DLBCL at diagnosis is independently associated with a worse clinical outcome (Journal of Experimental & Clinical Cancer Research 2018). These data have been recently confirmed in a validation patient cohort. Moreover, miR-22 plays a role as predictor of response to R-CHOP in these patients. To better understand the molecular basis of this clinical observation, we are studying miR22 in DLBCL cell lines. Our data show that a high extracellular/intracellular miR-22 ratio is significantly correlated to R-CHOP resistance in six different DLBCL cell lines (manuscript in preparation). In addition, the transfection of miR-22 mimic into these cell lines significantly affects their proliferation. To ensure a more reliable mirror of the complexity of the disease, we have performed a global expression profiling of circulating miRNAs in serum samples collected at diagnosis from a training cohort of responsive to R-CHOP versus primary refractory DLBCL patients. Our analysis shows 9 serum miRNAs differentially expressed (p<0.05) according to treatment response. Moreover, ROC curve analysis, shows an area under the curve >0.7 (p<0.05) demonstrating a predictive accuracy of the identified miRNA signature. These data suggest the possibility to early identify the chemo-resistant patients using this miRNA signature, with immediate consequence in therapeutic approach and pathogenesis understanding to these high-risk patients.
Transcriptional and epigenetic landscape in Multiple Myeloma (MM): the aim of this project is to identify the transcriptional and epigenetic mechanisms responsible for the resistance of MM patients treated with first-line chemotherapy schemes by characterizing the transcriptome in order to quantify neoplastic cells that have the same gene/epigenetic profile as the treatment-resistant cell population. A prospective multicenter clinical study is underway, recently approved by the Ethics Committee of our Institute, in collaboration with the Hematology Unit of the Tor Vergata University and Campus Bio-Medico University of Rome. The ultimate goal of this project is to be able to understand the epigenetic mechanisms underlying resistance to treatments for multiple myeloma and to be able to personalize the therapy based on the genomic background of the disease.
Biofilm in hematologic malignancies patients with bloodstream infection (BSI): Preliminary data on biofilm-producing K. pneumoniae strains showed a significant correlation between strong biofilm production and mortality rate in oncological patients (Front Cell infect Microbiol 2020). Based on these data, we aimed to analyze host and microbial risk factors and assesses their impact on BSI development and mortality. A total of 96 patients with hematologic malignancies developing a BSI during chemotherapeutic program have been so far analyzed. Our data show that the presence of strong biofilm-producing bacteria (P=0.013) and multidrug-resistant strains (P=0.006) were independent risk factors associated with 30-day mortality (manuscript in preparation). Biofilm production could represent an important factor significantly affecting survival in hematologic maligiancies patients.
Multiomics characterization of acute myeloid leukemia (AML): we are planning a collaborative study on behalf of Onco-Hematology Working Group of Alliance Against Cancer aimed to perform a multiomics analysis of hematologic malignancies. In particular, we aim to study through Whole-Exome Sequencing (WES) bone marrow samples of secondary and therapy-related AML patients treated with CPX-351, in order to better understand the genomic basis of treatment resistance in this high-risk group of patients.
Autologous stem cell transplantation (ASCT): the most widely used high-dose chemotherapy (HDC) before ASCT in lymphoma patients is BEAM regimen (carmustine, etoposide, cytarabine and melphalan), which is considered the gold standard both in United states and Europe. In Italy alternative regimens are FEAM or TEAM in which carmustine is replaced by fotemustine or thiotepa due to difficult suppling. We aimed to investigate in a retrospective fashion the comparison between BEAM, FEAM and TEAM regimen in terms of efficacy and safety in lymphoma patients undergoing ASCT. 414 consecutive lymphoma patients transplanted in three Italian Institutions (Sapienza University-Rome n=218, Regina Elena National Cancer Institute-Rome n=144, Cardarelli Hospital-Naples n=52) were analyzed: the 2 years PFS of BEAM and FEAM groups was significantly better than that of TEAM group, whereas no significant differences in terms of 2 years OS were reported. TEAM regimen seems to be better tolerated because of significantly lower rates of grade 3-4 oral mucositis, whereas infectious complications, other non-hematologic toxicities and TRM were similar among the three groups of patients. These data were presented at the 45th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) and published on Leukemia and Lymphoma in 2020.
Epidemiology of COVID-19 infection in patients with hematological malignancies (HM): currently very few data on COVID-19 infection in the specific subset of HM patients are available. To gain knowledge about this life-threatening disease in HM patients two observational studies have been launched in 2020: the first one coordinated by the Italian Hematology Alliance on behalf of the Società Italiana di Ematologia (SIE), the Gruppo Italiano Trapianto Midollo Osseo (GITMO), the Società Italiana di Ematologia Sperimentale (SIES), the Sorveglianza Epidemiologica Infezioni Fungine in Emopatie Maligne (SEIFEM) and the Fondazione Italiana Linfomi (FIL) and the second one by the European Haematology Association (EHA). Our Unit is involved in both studies that are multicenter retrospective/prospective, cohort, non-interventional observational studies with the primary objective to assess the epidemiology and outcomes of patients with HM infected of COVID-19 disease. Preliminary data have been published on Lancet Haematology in 2020: when comparing mortality in the study cohort with the Italian population with COVID-19, the standardised mortality ratio in the whole study population was 2.04; when comparing mortality in the study cohort with the non-COVID-19 cohort with HM the standardised mortality ratio was 41.3.
In 2015 the Unit created a web-based intra-net system of data collection: Progettoemat.it. This software system features diversified disease-specific data-bases designed to meet the most important control requirements of the clinical endpoints such as survival, relapse, effectiveness of treatment protocols and more. This system provides for the transfer of clinical data of about a thousand of patients from paper to electronic format. In recent months the database has been continuously updated and modified according to the needs which arise during data entry. The work that has preceded the actual data entry aimed at recovering all the records of patients who
died, were lost or left the follow-up. A computer file was then created in which 1500 patients are included. The Unit chose to start with two diseases: Follicular Lymphoma (FL) and Diffuse Large Cell Lymphoma (DLBCL). To date 187 patients were included with FL and 336 patients with DLBCL. In September 2016 data-entry started about patients with multiple myeloma (so far 100 records were filed). The activity of the Secretariat and Data Manager also provides the database update of DMT and satisfaction questionnaires.
The patient’s enrollment in the project “Psychological Functioning and quality of life after autologous stem cell transplantation in patients with onco-hematological disease” continued in 2019. The objective of this prospective longitudinal study is to assess the impact of graft on the quality of life and psychological functioning of adult patients undergoing ASCT, and to identify potential demographic, clinical, and psychological predictors of variables under study. The hypothesis is that patients with high scores of physical well-being, more education, lower levels of anxiety and depression, more resilient, more adaptive coping strategies, higher self-efficacy and increased social support before transplantation are those with better quality of life and psychological functioning immediately after transplantation and in a one year follow-up. In 2019 we completed the enrollment in the study for an overall population of 80 patients; in 2020 we continued follow-up evaluation of all patients enrolled in the study and administered a total of 286 questionnaires for measuring the quality of life, the perceived social support, the psychological distress, the resilience and self-efficacy before and after transplant procedure. Data analysis and manuscript preparation is ongoing.
As for clinical trials, during the 2020, 48 clinical research protocols proposed by Hematology and Transplant Unit and approved by Regina Elena I.F.O. Ethics Committee have been open to recruitment and 468 patients have been enrolled.