235 results on '"Algeri M."'
Search Results
2. EFFECT OF ANTI-PCSK9 ANTIBODIES ON ARTERY STRUCTURE AND FUNCTION: THE NIGUARDA HOSPITAL COHORT
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Maloberti, A, Toscani, G, Busti, A, Tognola, C, Intravaia, R, De Censi, L, Galasso, M, Daus, F, Giani, V, Gualini, E, Garofani, I, Riccio, A, Biolcati, M, Fabbri, S, Algeri, M, Merlini, P, Giannattasio, C, Morelli, M, Maloberti, Alessandro, Toscani, Giorgio, Busti, Andrea, Tognola, Chiara, Intravaia, Rita Cristina Mi, De Censi, Lorenzo, Galasso, Michele, Daus, Franesca, Giani, Valentina, Gualini, Elena, Garofani, Ilaria, Riccio, Alfonso, Biolcati, Marco, Fabbri, Saverio, Algeri, Michela, Merlini, Piera, Giannattasio, Cristina, Morelli, Martina, Maloberti, A, Toscani, G, Busti, A, Tognola, C, Intravaia, R, De Censi, L, Galasso, M, Daus, F, Giani, V, Gualini, E, Garofani, I, Riccio, A, Biolcati, M, Fabbri, S, Algeri, M, Merlini, P, Giannattasio, C, Morelli, M, Maloberti, Alessandro, Toscani, Giorgio, Busti, Andrea, Tognola, Chiara, Intravaia, Rita Cristina Mi, De Censi, Lorenzo, Galasso, Michele, Daus, Franesca, Giani, Valentina, Gualini, Elena, Garofani, Ilaria, Riccio, Alfonso, Biolcati, Marco, Fabbri, Saverio, Algeri, Michela, Merlini, Piera, Giannattasio, Cristina, and Morelli, Martina
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- 2024
3. HYPERTRIGLYCERIDEMIA IN PATIENTS WITH ACUTE AND CHRONIC CORONARY SYNDROME: PREVALENCE AND THEIR ASSOCIATION WITH EXTREME CARDIOVASCULAR RISK AND LEFT VENTRICULAR FUNCTION
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Maloberti, A, Rosa, A, Toscani, G, Caccia, A, Gualini, E, Pezzoli, S, Morelli, M, Busti, A, Colombo, V, Tognola, C, Algeri, M, Intravaia, R, Pirola, R, Giannattasio, C, Garofani, I, Maloberti, Alessandro, Rosa, Antonio La, Toscani, Giorgio, Caccia, Andrea, Gualini, Elena, Pezzoli, Stefano, Morelli, Martina, Busti, Andrea, Colombo, Valentina, Tognola, Chiara, Algeri, Michela, Intravaia, Rita Cristina My, Pirola, Roberto, Giannattasio, Cristina, Garofani, Ilaria, Maloberti, A, Rosa, A, Toscani, G, Caccia, A, Gualini, E, Pezzoli, S, Morelli, M, Busti, A, Colombo, V, Tognola, C, Algeri, M, Intravaia, R, Pirola, R, Giannattasio, C, Garofani, I, Maloberti, Alessandro, Rosa, Antonio La, Toscani, Giorgio, Caccia, Andrea, Gualini, Elena, Pezzoli, Stefano, Morelli, Martina, Busti, Andrea, Colombo, Valentina, Tognola, Chiara, Algeri, Michela, Intravaia, Rita Cristina My, Pirola, Roberto, Giannattasio, Cristina, and Garofani, Ilaria
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- 2024
4. Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation
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Rizzo, M. I., Tomao, L., Tedesco, S., Cajozzo, M., Esposito, M., De Stefanis, C., Ferranti, A. M., Mezzogori, D., Palmieri, A., Pozzato, G., Algeri, M., Locatelli, F., Leone, L., and Zama, M.
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- 2021
- Full Text
- View/download PDF
5. Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol
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Maloberti, A, Intravaia, R, Mancusi, C, Cesaro, A, Golia, E, Ilaria, F, Coletta, S, Merlini, P, De Chiara, B, Bernasconi, D, Algeri, M, Ossola, P, Ciampi, C, Riccio, A, Tognola, C, Ardissino, M, Inglese, E, Scaglione, F, Calabro, P, De Luca, N, Giannattasio, C, Maloberti A., Intravaia R. C. M., Mancusi C., Cesaro A., Golia E., Ilaria F., Coletta S., Merlini P., De Chiara B., Bernasconi D., Algeri M., Ossola P., Ciampi C., Riccio A., Tognola C., Ardissino M., Inglese E., Scaglione F., Calabro P., De Luca N., Giannattasio C., Maloberti, A, Intravaia, R, Mancusi, C, Cesaro, A, Golia, E, Ilaria, F, Coletta, S, Merlini, P, De Chiara, B, Bernasconi, D, Algeri, M, Ossola, P, Ciampi, C, Riccio, A, Tognola, C, Ardissino, M, Inglese, E, Scaglione, F, Calabro, P, De Luca, N, Giannattasio, C, Maloberti A., Intravaia R. C. M., Mancusi C., Cesaro A., Golia E., Ilaria F., Coletta S., Merlini P., De Chiara B., Bernasconi D., Algeri M., Ossola P., Ciampi C., Riccio A., Tognola C., Ardissino M., Inglese E., Scaglione F., Calabro P., De Luca N., and Giannattasio C.
- Abstract
Introduction: Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called “extreme CV risk”). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs. Aim. Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. Aim: Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. Methods: We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients’ clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers. Conclusions: Our study proposal was granted by the European Union PNRR M6/C2 call.
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- 2023
6. The Development of New Agents for Post-Hematopoietic Stem Cell Transplantation Non-Infectious Complications in Children
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Ilan, U, Brivio, E, Algeri, M, Balduzzi, A, Gonzalez-Vincent, M, Locatelli, F, Zwaan, C, Baruchel, A, Lindemans, C, Bautista, F, Ilan U., Brivio E., Algeri M., Balduzzi A., Gonzalez-Vincent M., Locatelli F., Zwaan C. M., Baruchel A., Lindemans C., Bautista F., Ilan, U, Brivio, E, Algeri, M, Balduzzi, A, Gonzalez-Vincent, M, Locatelli, F, Zwaan, C, Baruchel, A, Lindemans, C, Bautista, F, Ilan U., Brivio E., Algeri M., Balduzzi A., Gonzalez-Vincent M., Locatelli F., Zwaan C. M., Baruchel A., Lindemans C., and Bautista F.
- Abstract
Hematopoietic stem cell transplantation (HSCT) is often the only curative treatment option for patients suffering from various types of malignant diseases and some non-cancerous conditions. Nevertheless, it is associated with a high risk of complications leading to transplant-related mortality and long-term morbidity. An increasing number of therapeutic and prevention strategies have been developed over the last few years to tackle the complications arising in patients receiving an HSCT. These strategies have been mainly carried out in adults and some are now being translated into children. In this manuscript, we review the recent advancements in the development and implementation of treatment options for post-HSCT non-infectious complications in pediatric patients with leukemia and other non-malignant conditions, with a special attention on the new agents available within clinical trials. We focused on the following conditions: graft failure, prevention of relapse and early interventions after detection of minimal residual disease positivity following HSCT in acute lymphoblastic and myeloid leukemia, chronic graft versus host disease, non-infectious pulmonary complications, and complications of endothelial origin.
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- 2023
7. Hematopoietic Stem/Progenitor Cells and Engineering: LONG-TERM DATA ON IMMUNE MONITORING OF CHILDREN GIVEN TCRαβ/CD19 CELL DEPLETED HLA-HAPLOIDENTICAL STEM TRANSPLANTATION (HAPLO-HSCT)
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Bertaina, V., primary, Sborgia, R., additional, Marini, O., additional, De Luca, C., additional, Carta, R., additional, Becilli, M., additional, Pagliara, D., additional, Quagliarella, F., additional, Lucarelli, B., additional, Boccieri, E., additional, Velardi, E., additional, Algeri, M., additional, Merli, P., additional, Galaverna, F., additional, and Locatelli, F., additional
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- 2023
- Full Text
- View/download PDF
8. Natural history of Ras‐associated autoimmune leukoproliferative disorder: A 20‐year follow‐up of a NRAS‐mutated patient excluding a malignant progression.
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Rivalta, B., Attardi, E., Cifaldi, C., Rosti, V., Pacillo, L., Hajrullaj, H., Di Cesare, S., Amodio, D., Algeri, M., Luciani, M., Barzaghi, F., Finocchi, A., Di Matteo, G., Aiuti, A., Locatelli, F., Voso, M. T., Palumbo, G., and Cancrini, C.
- Subjects
NATURAL history ,AUTOIMMUNE diseases ,PELVIC inflammatory disease ,MONONUCLEAR leukocytes ,CORD blood transplantation - Abstract
This article explores the natural history of Ras-associated autoimmune leukoproliferative disorder (RALD), a rare condition caused by mutations in the NRAS or KRAS genes. RALD is characterized by lymphadenopathy, splenomegaly, persistent leucocytosis, and autoimmune symptoms. The article discusses the challenges in diagnosing and monitoring RALD patients, as some may develop juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML), while others may experience spontaneous improvement. The article presents a case study of a 22-year-old male with RALD, providing a clinical history and a detailed analysis of his immune profile. The study emphasizes the importance of exploring somatic gene variants in patients with specific immunological profiles and suggests that an integrated approach combining clinical parameters, functional assays, and longitudinal assessment of additional mutations may help predict disease progression. The findings contribute to the understanding of RALD and may enhance monitoring and treatment strategies for patients with this rare condition. [Extracted from the article]
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- 2024
- Full Text
- View/download PDF
9. Acupuncture in Arterial Hypertension: Evaluation of its Efficacy with Both Office and Ambulatory Blood Pressure Measurements
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Migliarese, C, Maloberti, A, Gatto, R, Algeri, M, Scarpellini, S, Giannattasio, C, Migliarese C., Maloberti A., Gatto R., Algeri M., Scarpellini S., Giannattasio C., Migliarese, C, Maloberti, A, Gatto, R, Algeri, M, Scarpellini, S, Giannattasio, C, Migliarese C., Maloberti A., Gatto R., Algeri M., Scarpellini S., and Giannattasio C.
- Abstract
Introduction: A possible alternative to pharmacological antihypertensive therapies in grade 1 low risk hypertensive patients or in those experienced drugs adverse effects could be acupuncture. Aim: we focused on its possible effects on BP both as Office BP (OBP) and as Ambulatory BP Monitoring (ABPM) evaluating it before starting a 6 weeks twice weekly (total 12 session) acupuncture cycle and after 2 months from its completion. Methods: in this prospective study we treated with acupuncture 45 patients: 24 of them presents high-normal BP values and low cardiovascular risk while 21 patients were on anti-hypertensive drug with slightly uncontrolled BP values (from 140 to 145 mmHg for Systolic BP—SBP—and/or from 90 to 95 mmHg for Diastolic BP—DBP). Results: regarding SBP, a significant reduction have been observed for office values (from 134.2 ± 15.7 to 125.1 ± 12.2, p = 0.03), and for ABPM 24 h (from 131.1 ± 10.7 to 126.0 ± 10.1, p = 0.01) and day-time values (from 134.7 ± 10.5 to 127.1 ± 18.4, p = 0.02). For DBP, only ABPM 24 h and day-time values showed significant changes (from 85.3 ± 9.1 to 82.1 ± 7.5, p = 0.03; and from 88.5 ± 9.3 to 85.7 ± 7.8, p = 0.02). Within session SBP decrease was − 5.8 mmHg (-3.75%) during the first session while it falls to – 2.1 mmHg (– 1.25%) and stands firmly under 2 mmHg for all the next session. At the last session SBP reduction was − 1.9 mmHg (– 1.6%). Conclusions: we found a significant reduction in office, 24 h and day-time ABPM SBP determined by a 6-weeks twice weekly acupuncture cycle that lasts at least for the first two months after its completion.
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- 2022
10. Elevated Serum Urea-to-Creatinine Ratio and In-Hospital Death in Patients with Hyponatremia Hospitalized for COVID-19
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Regolisti, G, Rebora, P, Occhino, G, Lieti, G, Molon, G, Maloberti, A, Algeri, M, Giannattasio, C, Valsecchi, M, Genovesi, S, Regolisti, Giuseppe, Rebora, Paola, Occhino, Giuseppe, Lieti, Giulia, Molon, Giulio, Maloberti, Alessandro, Algeri, Michela, Giannattasio, Cristina, Valsecchi, Maria Grazia, Genovesi, Simonetta, Regolisti, G, Rebora, P, Occhino, G, Lieti, G, Molon, G, Maloberti, A, Algeri, M, Giannattasio, C, Valsecchi, M, Genovesi, S, Regolisti, Giuseppe, Rebora, Paola, Occhino, Giuseppe, Lieti, Giulia, Molon, Giulio, Maloberti, Alessandro, Algeri, Michela, Giannattasio, Cristina, Valsecchi, Maria Grazia, and Genovesi, Simonetta
- Abstract
Hyponatremia is associated with adverse outcomes in hospitalized patients. An elevated value of the serum urea-to-creatinine ratio (UCR) has been proposed as a proxy of hypovolemia. The aim of this study was to investigate the relationship between the UCR and in-hospital death in patients hospitalized with COVID-19 and hyponatremia. We studied 258 patients admitted for COVID-19 between January 2020 and May 2021 with serum sodium at < 135 mmol/L. The primary end-point was all-cause mortality. A 5-unit increase in the serum UCR during hospital stays was associated with an 8% increase in the hazard of all-cause death (HR = 1.08, 95% CI: 1.03–1.14, p = 0.001) after adjusting for potential confounders. In patients with a UCR > 40 at baseline, a > 10 mmol/L increase in serum sodium values within the first week of hospitalization was associated with higher odds of in-hospital death (OR = 2.93, 95% CI: 1.03–8.36, p = 0.044) compared to patients who experienced a < 10 mmol/L change. This was not observed in patients with a UCR < 40. Hypovolemia developing during hospital stays in COVID-19 patients with hyponatremia detected at hospital admission bears an adverse prognostic impact. Moreover, in hypovolemic patients, a > 10 mmol/L increase in serum sodium within the first week of hospital stays may further worsen the in-hospital prognosis.
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- 2023
11. Achievement of operational tolerance in a pediatric liver transplant recipient following successful hematopoietic stem cell transplantation from a different donor
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Algeri, M., Velardi, E., Spada, M., Galaverna, F., Carta, R., Vinti, L., Palumbo, G., Gaspari, S., Pietrobattista, A., Boccieri, E., Becilli, M., Francalanci, P., Bertaina, V., Merli, P., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Algeri, M., Velardi, E., Spada, M., Galaverna, F., Carta, R., Vinti, L., Palumbo, G., Gaspari, S., Pietrobattista, A., Boccieri, E., Becilli, M., Francalanci, P., Bertaina, V., Merli, P., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Hematopoietic stem cell transplantation (HSCT)–based approaches are increasingly investigated strategies to induce tolerance in recipients of solid allografts. However, in the majority of cases, these approaches rely on the infusion of hematopoietic stem cells recovered from the same solid organ donor. In this report, we describe the case of a boy who received liver transplantation from a deceased donor, who had successfully underwent allogeneic HSCT from an unrelated donor for hepatitis-associated aplastic anemia. In this patient, it was possible to permanently withdraw post-HSCT immune suppression without causing any sign of liver graft dysfunction. To the best of our knowledge, this is the first case of operational tolerance documented in a patient who received combined liver transplantation and HSCT from different donors.
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- 2023
12. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma
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Del Bufalo, F., De Angelis, B., Caruana, I., Del Baldo, G., De Ioris, M. A., Serra, A., Mastronuzzi, A., Cefalo, M. G., Pagliara, D., Amicucci, M., Li Pira, G., Leone, G., Bertaina, V., Sinibaldi, M., Di Cecca, S., Guercio, M., Abbaszadeh, Z., Iaffaldano, L., Gunetti, M., Iacovelli, S., Bugianesi, R., Macchia, S., Algeri, M., Merli, P., Galaverna, F., Abbas, R., Garganese, M. C., Villani, M. F., Colafati, G. S., Bonetti, F., Rabusin, M., Perruccio, K., Folsi, V., Quintarelli, C., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Del Bufalo, F., De Angelis, B., Caruana, I., Del Baldo, G., De Ioris, M. A., Serra, A., Mastronuzzi, A., Cefalo, M. G., Pagliara, D., Amicucci, M., Li Pira, G., Leone, G., Bertaina, V., Sinibaldi, M., Di Cecca, S., Guercio, M., Abbaszadeh, Z., Iaffaldano, L., Gunetti, M., Iacovelli, S., Bugianesi, R., Macchia, S., Algeri, M., Merli, P., Galaverna, F., Abbas, R., Garganese, M. C., Villani, M. F., Colafati, G. S., Bonetti, F., Rabusin, M., Perruccio, K., Folsi, V., Quintarelli, C., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. Methods: In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01). Results: A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×106 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×106 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively. Conclusions: The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others
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- 2023
13. Human leukocyte antigen evolutionary divergence influences outcomes of paediatric patients and young adults affected by malignant disorders given allogeneic haematopoietic stem cell transplantation from unrelated donors
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Merli, P., Crivello, P., Strocchio, L., Pinto, R. M., Algeri, M., Del Bufalo, F., Pagliara, D., Becilli, M., Carta, R., Gaspari, S., Galaverna, F., Quagliarella, F., Boz, G., Catanoso, M. L., Boccieri, E., Troiano, M., Fleischhauer, K., Andreani, M., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Merli, P., Crivello, P., Strocchio, L., Pinto, R. M., Algeri, M., Del Bufalo, F., Pagliara, D., Becilli, M., Carta, R., Gaspari, S., Galaverna, F., Quagliarella, F., Boz, G., Catanoso, M. L., Boccieri, E., Troiano, M., Fleischhauer, K., Andreani, M., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9–10/10 HLA-matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, using the locus median to stratify patients with ‘high’ or ‘low’ HED. Patients with high HED-B and -DRB1 showed significantly improved disease-free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.
- Published
- 2023
14. The Development of New Agents for Post-Hematopoietic Stem Cell Transplantation Non-Infectious Complications in Children
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Ilan, U., Brivio, E., Algeri, M., Balduzzi, A., Gonzalez-Vincent, M., Locatelli, Franco, Zwaan, C. M., Baruchel, A., Lindemans, C., Bautista, F., Locatelli F. (ORCID:0000-0002-7976-3654), Ilan, U., Brivio, E., Algeri, M., Balduzzi, A., Gonzalez-Vincent, M., Locatelli, Franco, Zwaan, C. M., Baruchel, A., Lindemans, C., Bautista, F., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Hematopoietic stem cell transplantation (HSCT) is often the only curative treatment option for patients suffering from various types of malignant diseases and some non-cancerous conditions. Nevertheless, it is associated with a high risk of complications leading to transplant-related mortality and long-term morbidity. An increasing number of therapeutic and prevention strategies have been developed over the last few years to tackle the complications arising in patients receiving an HSCT. These strategies have been mainly carried out in adults and some are now being translated into children. In this manuscript, we review the recent advancements in the development and implementation of treatment options for post-HSCT non-infectious complications in pediatric patients with leukemia and other non-malignant conditions, with a special attention on the new agents available within clinical trials. We focused on the following conditions: graft failure, prevention of relapse and early interventions after detection of minimal residual disease positivity following HSCT in acute lymphoblastic and myeloid leukemia, chronic graft versus host disease, non-infectious pulmonary complications, and complications of endothelial origin.
- Published
- 2023
15. Lipoprotein(a): Cardiovascular Disease, Aortic Stenosis and New Therapeutic Option
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Maloberti, A, Fabbri, S, Colombo, V, Gualini, E, Monticelli, M, Daus, F, Busti, A, Galasso, M, De Censi, L, Algeri, M, Merlini, P, Giannattasio, C, Maloberti, Alessandro, Fabbri, Saverio, Colombo, Valentina, Gualini, Elena, Monticelli, Massimiliano, Daus, Francesca, Busti, Andrea, Galasso, Michele, De Censi, Lorenzo, Algeri, Michela, Merlini, Piera Angelica, Giannattasio, Cristina, Maloberti, A, Fabbri, S, Colombo, V, Gualini, E, Monticelli, M, Daus, F, Busti, A, Galasso, M, De Censi, L, Algeri, M, Merlini, P, Giannattasio, C, Maloberti, Alessandro, Fabbri, Saverio, Colombo, Valentina, Gualini, Elena, Monticelli, Massimiliano, Daus, Francesca, Busti, Andrea, Galasso, Michele, De Censi, Lorenzo, Algeri, Michela, Merlini, Piera Angelica, and Giannattasio, Cristina
- Abstract
Atherosclerosis is a chronic and progressive inflammatory process beginning early in life with late clinical manifestation. This slow pathological trend underlines the importance to early identify high-risk patients and to treat intensively risk factors to prevent the onset and/or the progression of atherosclerotic lesions. In addition to the common Cardiovascular (CV) risk factors, new markers able to increase the risk of CV disease have been identified. Among them, high levels of Lipoprotein(a)—Lp(a)—lead to very high risk of future CV diseases; this relationship has been well demonstrated in epidemiological, mendelian randomization and genome-wide association studies as well as in meta-analyses. Recently, new aspects have been identified, such as its association with aortic stenosis. Although till recent years it has been considered an unmodifiable risk factor, specific drugs have been developed with a strong efficacy in reducing the circulating levels of Lp(a) and their capacity to reduce subsequent CV events is under testing in ongoing trials. In this paper we will review all these aspects: from the synthesis, clearance and measurement of Lp(a), through the findings that examine its association with CV diseases and aortic stenosis to the new therapeutic options that will be available in the next years.
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- 2023
16. A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome
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Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, Franco, Remuzzi, G., Ruggenenti, P., Locatelli F. (ORCID:0000-0002-7976-3654), Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, Franco, Remuzzi, G., Ruggenenti, P., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
BACKGROUNDSevere forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODSWe performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTSSixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults.In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusionCONCLUSIONTreatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.TRIAL REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.
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- 2023
17. Allogeneic, donor-derived, second-generation, CD19-directed CAR-T cells for the treatment of pediatric relapsed/refractory BCP-ALL
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del Bufalo, F., Becilli, M., Rosignoli, C., De Angelis, B., Algeri, M., Hanssens, L., Gunetti, M., Iacovelli, S., Li Pira, G., Girolami, E., Leone, G., Lazzaro, S., Bertaina, V., Sinibaldi, M., Di Cecca, S., Iaffaldano, L., Kunkele, A., Boccieri, E., Del Baldo, G., Pagliara, D., Merli, P., Carta, R., Quintarelli, C., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), del Bufalo, F., Becilli, M., Rosignoli, C., De Angelis, B., Algeri, M., Hanssens, L., Gunetti, M., Iacovelli, S., Li Pira, G., Girolami, E., Leone, G., Lazzaro, S., Bertaina, V., Sinibaldi, M., Di Cecca, S., Iaffaldano, L., Kunkele, A., Boccieri, E., Del Baldo, G., Pagliara, D., Merli, P., Carta, R., Quintarelli, C., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Autologous CD19-directed chimeric antigen receptor (CAR)-T cells have shown unprecedented efficacy in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, patients either relapsing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or displaying profound lymphopenia and/or rapidly progressing disease often cannot access autologous products. These hurdles may be overcome by allogeneic, donor-derived CAR-T cells. We tested donor-derived T cells transduced with a second-generation (4.1BB) CD19-directed CAR for treatment of patients with BCP-ALL in a hospital-exemption setting. Two constructs were tested: a retroviral construct incorporating the suicide gene inducible caspase-9 (CD19-CAR–Retro_ALLO) first and then a lentiviral construct and an automated, Prodigy-based manufacturing process (CD19-CAR–Lenti_ALLO). Thirteen children/young adults received ALLO–CAR-T cells between March 2021 and October 2022. Doses ranged between 1.0 × 106 and 3.0 × 106 CAR-T cells per kg. The toxicity profile was comparable with that of autologous CAR-T cells, characterized mainly by cytopenia, cytokine release syndrome (maximum grade 1), and grade 2 immune-effector cell–associated neurotoxicity syndrome. One case of acute graft-versus-host disease (GVHD) occurred and was rapidly controlled with steroids and ruxolitinib. None of the other patients, including 3 given ALLO–CAR-T cells from an HLA-haploidentical donor, experienced GVHD. Two patients received ALLO–CAR-T cells before HSCT and showed a significant expansion of CAR-T cells without any sign of GVHD. All patients obtained complete remission (CR) with absence of minimal residual disease in the bone marrow. With a median follow-up of 12 months (range, 5-21), 8 of 13 patients maintained CR. Allogeneic anti-CD19 CAR-T cells can effectively treat highly refractory BCP-ALL relapsing after allo-HSCT without showing increased toxicity as compared with autologous CAR-T cells.
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- 2023
18. Busulfan–fludarabine- or treosulfan–fludarabine-based myeloablative conditioning for children with thalassemia major
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Luftinger, R., Zubarovskaya, N., Galimard, J.E., Cseh, A., Salzer, E., Locatelli, F., Algeri, M., Yesilipek, A., Fuente, J. de la, Isgro, A., Alseraihy, A., Angelucci, E., Smiers, F.J., Nasa, G.L., Zecca, M., Fisgin, T., Unal, E., Kleinschmidt, K., Peters, C., Lankester, A., and Corbacioglu, S.
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Male ,Transplantation Conditioning ,Adolescent ,Treosulfan ,beta-Thalassemia ,Infant ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Hematology ,General Medicine ,Myeloablative Agonists ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Child, Preschool ,Humans ,Female ,Child ,Thalassemia major ,Busulfan ,Immunosuppressive Agents ,Vidarabine ,Retrospective Studies ,Conditioning - Abstract
Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.
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- 2022
19. COVID-19 and cardiovascular system: not only heart but also vascular. The effects of the infection on arterial stiffness
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Maloberti, A, primary, Gualini, E, additional, Scarpellini, S, additional, Algeri, M, additional, Biolcati, M, additional, Grasso, E, additional, Tognola, C, additional, and Moreo, A, additional
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- 2022
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20. Atrial fibrillation incidence in SARS-CoV-2 infected patients: predictors and relationship with in-hospital mortality
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Maloberti, A, primary, Giannattasio, C, additional, Rebora, P, additional, Occhino, G, additional, Ughi, N, additional, Fabbri, S, additional, Cartella, I, additional, Algeri, M, additional, Scarpellini, S, additional, Rossetti, C, additional, Epis, O M, additional, Molon, G, additional, Bonfanti, P, additional, Valsecchi, M G, additional, and Genovesi, S, additional
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- 2022
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21. Atrial fibrillation incidence in SARS-CoV-2 infected patients: Predictors and relationship with in-hospital mortality
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Maloberti, A., primary, Giannattasio, C., additional, Rebora, P., additional, Occhino, G., additional, Ughi, N., additional, Rizzo, J., additional, Fabbri, S., additional, Leidi, F., additional, Cartella, I., additional, Algeri, M., additional, Scarpellini, S., additional, Rossetti, C., additional, Epis, O.M., additional, Molon, G., additional, Bonfanti, P., additional, Valsecchi, M.G., additional, and Genovesi, S., additional
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- 2022
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22. COVID-19 and cardiovascular system: Not only heart but also vascular. The effects of the infection on arterial stiffness
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Maloberti, A., primary, Gualini, E., additional, Scarpellini, S., additional, Algeri, M., additional, Biolcati, M., additional, Grasso, E., additional, Tognola, C., additional, Moreo, A., additional, and Giannattasio, C., additional
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- 2022
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23. Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts
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Quintarelli, C, Guercio, M, Manni, S, Boffa, I, Sinibaldi, M, DI Cecca, S, Caruso, S, Abbaszadeh, Z, Camera, A, Cembrola, B, Ciccone, R, Orfao, A, Martin-Martin, L, Gutierrez-Herrero, S, Herrero-Garcia, M, Cazzaniga, G, Nunes, V, Songia, S, Marcatili, P, Marin, F, Ruella, M, Bertaina, V, Vinti, L, Del Bufalo, F, Algeri, M, Merli, P, De Angelis, B, Locatelli, F, Quintarelli C., Guercio M., Manni S., Boffa I., Sinibaldi M., DI Cecca S., Caruso S., Abbaszadeh Z., Camera A., Cembrola B., Ciccone R., Orfao A., Martin-Martin L., Gutierrez-Herrero S., Herrero-Garcia M., Cazzaniga G., Nunes V., Songia S., Marcatili P., Marin F. I., Ruella M., Bertaina V., Vinti L., Del Bufalo F., Algeri M., Merli P., De Angelis B., Locatelli F., Quintarelli, C, Guercio, M, Manni, S, Boffa, I, Sinibaldi, M, DI Cecca, S, Caruso, S, Abbaszadeh, Z, Camera, A, Cembrola, B, Ciccone, R, Orfao, A, Martin-Martin, L, Gutierrez-Herrero, S, Herrero-Garcia, M, Cazzaniga, G, Nunes, V, Songia, S, Marcatili, P, Marin, F, Ruella, M, Bertaina, V, Vinti, L, Del Bufalo, F, Algeri, M, Merli, P, De Angelis, B, Locatelli, F, Quintarelli C., Guercio M., Manni S., Boffa I., Sinibaldi M., DI Cecca S., Caruso S., Abbaszadeh Z., Camera A., Cembrola B., Ciccone R., Orfao A., Martin-Martin L., Gutierrez-Herrero S., Herrero-Garcia M., Cazzaniga G., Nunes V., Songia S., Marcatili P., Marin F. I., Ruella M., Bertaina V., Vinti L., Del Bufalo F., Algeri M., Merli P., De Angelis B., and Locatelli F.
- Abstract
Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk of CD19-/CAR+ leukemic relapse due to inadvertent transduction of leukemia cells. BackgroundMethods We evaluated the impact of a high percentage of leukemia blast contamination in patient-derived starting material (SM) on CAR T-cell drug product (DP) manufacturing. In vitro as well as in vivo models were employed to identify characteristics of the construct associated with better profile of safety in case of inadvertent B-cell leukemia transduction during CAR T-cell manufacturing. Results The presence of large amounts of CD19+ cells in SM did not affect the transduction level of DPs, as well as the CAR T-cell rate of expansion at the end of standard production of 14 days. DPs were deeply characterized by flow cytometry and molecular biology for Ig-rearrangements, showing that the level of B-cell contamination in DPs did not correlate with the percentage of CD19+ cells in SM, in the studied patient cohort. Moreover, we investigated whether CAR design may affect the control of CAR+ leukemia cells. We provided evidences that CAR.CD19 short linker (SL) prevents complete epitope masking in CD19+CAR+ leukemia cells and we demonstrated in vitro and in vivo that CD19 +CAR(SL)+leukemic cells are killed by CAR.CD19 T-cells. Conclusions Taken together, these data suggest that a VL-VH SL may result in a safe CAR-T product, even when manufacturing starts from biological materials characterized by heavy contamination of leukemia blasts.
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- 2021
24. The role of uric acid in acute and chronic coronary syndromes
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Maloberti, A, Biolcati, M, Ruzzenenti, G, Giani, V, Leidi, F, Monticelli, M, Algeri, M, Scarpellini, S, Nava, S, Soriano, F, Oreglia, J, Sacco, A, Morici, N, Oliva, F, Piani, F, Borghi, C, Giannattasio, C, Maloberti A., Biolcati M., Ruzzenenti G., Giani V., Leidi F., Monticelli M., Algeri M., Scarpellini S., Nava S., Soriano F., Oreglia J., Sacco A., Morici N., Oliva F., Piani F., Borghi C., Giannattasio C., Maloberti, A, Biolcati, M, Ruzzenenti, G, Giani, V, Leidi, F, Monticelli, M, Algeri, M, Scarpellini, S, Nava, S, Soriano, F, Oreglia, J, Sacco, A, Morici, N, Oliva, F, Piani, F, Borghi, C, Giannattasio, C, Maloberti A., Biolcati M., Ruzzenenti G., Giani V., Leidi F., Monticelli M., Algeri M., Scarpellini S., Nava S., Soriano F., Oreglia J., Sacco A., Morici N., Oliva F., Piani F., Borghi C., and Giannattasio C.
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Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.
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- 2021
25. The efficacy and safety of allogeneic stem cell transplantation in Mevalonate Kinase Deficiency
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Jeyaratnam, J., Faraci, M., Gennery, A.R., Drabko, K., Algeri, M., Morimoto, A., Sirait, T., Lankester, A.C., Albert, M., Neven, B., Frenkel, J., and EBMT Inborn Errors Working Party
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Auto-inflammation ,Therapeutic options ,Inborn metabolic disease ,Mevalonic aciduria ,Allogeneic stem cell transplantation - Abstract
Objectives Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients, sometimes with promising results. In view of the scarcity of data, this study aims to analyse the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) to give a more complete overview of this treatment. Methods This multicentre retrospective study on behalf of the European Society for Blood and Marrow Transplantation aimed to include all MKD patients who had undergone allogeneic HSCT. All centres related to EMBT and centres that have reported cases of allogeneic HSCT in the literature were contacted via the EBMT data office. Results We analyzed 9 patients (5 male). Treosulfan based conditioning was the most frequently used conditioning regimen. Engraftment occurred in all but one patient. Source of stem cells was cord blood (n = 2), peripheral blood stem cells (n = 4) and bone marrow (n = 5). Two patients needed a second transplantation due to an incomplete response or primary graft failure. Seven patients went into complete remission after stem cell transplantation. At final follow-up these patients reported no symptoms of MKD. Four patients suffered from grade II-IV acute graft-versus-host disease (GvHD). During follow-up two patients died due to transplantation related complications. Conclusion In conclusion, allogeneic stem cell transplantation represents an effective treatment for the most severely affected MKD patients. However, treatment-related morbidity and mortality are significant. Transplantation may be justified in patients with a severe disease course on conservative therapy.
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- 2022
26. P1361: TREATMENT OF SEVERE STEROID-REFRACTORY ACUTE GVHD WITH MESENCHYMAL STROMAL CELLS: RESULTS OF THE PHASE III RANDOMIZED DOUBLE-BLIND MULTI-CENTER HOVON-113 TRIAL
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Oosten, L., primary, van Pel, M., additional, van der Holt, B., additional, Bach, E., additional, Cross, M., additional, Roelofs, H., additional, Meij, P., additional, Wieles, B., additional, Zwaginga, J. J., additional, Lankester, A., additional, Veelken, H., additional, Platzbecker, U., additional, Sanchez-Guijo, F., additional, Algeri, M., additional, Locatelli, F., additional, Devos, T., additional, Cornelissen, J., additional, Niederwieser, D., additional, and Fibbe, W., additional
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- 2022
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27. P16 ATRIAL FIBRILLATION INCIDENCE IN SARS–COV–2 INFECTED PATIENTS: PREDICTORS AND RELATIONSHIP WITH IN–HOSPITAL MORTALITY
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Maloberti, A, primary, Giannattasio, C, additional, Rebora, P, additional, Occhino, G, additional, Ughi, N, additional, Rizzo, J, additional, Fabbri, S, additional, Leidi, F, additional, Cartella, I, additional, Algeri, M, additional, Scarpellini, S, additional, Rossetti, C, additional, Epis, O, additional, Molon, G, additional, Bonfanti, P, additional, Valsecchi, M, additional, and Genovesi, S, additional
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- 2022
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28. P389 COVID–19 AND CARDIOVASCULAR SYSTEM: NOT ONLY HEART BUT ALSO VASCULAR. THE EFFECTS OF THE INFECTION ON ARTERIAL STIFFNESS
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Maloberti, A, primary, Gualini, E, additional, Scarpellini, S, additional, Algeri, M, additional, Biolcati, M, additional, Grasso, E, additional, Tognola, C, additional, Moreo, A, additional, and Giannattasio, C, additional
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- 2022
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29. Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients
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Maloberti, A, Giannattasio, C, Rebora, P, Occhino, G, Ughi, N, Biolcati, M, Gualini, E, Rizzi, J, Algeri, M, Giani, V, Rossetti, C, Epis, O, Molon, G, Beltrame, A, Bonfanti, P, Valsecchi, M, Genovesi, S, Maloberti, Alessandro, Giannattasio, Cristina, Rebora, Paola, Occhino, Giuseppe, Ughi, Nicola, Biolcati, Marco, Gualini, Elena, Rizzi, Jacopo Giulio, Algeri, Michela, Giani, Valentina, Rossetti, Claudio, Epis, Oscar Massimiliano, Molon, Giulio, Beltrame, Anna, Bonfanti, Paolo, Valsecchi, Maria Grazia, Genovesi, Simonetta, Maloberti, A, Giannattasio, C, Rebora, P, Occhino, G, Ughi, N, Biolcati, M, Gualini, E, Rizzi, J, Algeri, M, Giani, V, Rossetti, C, Epis, O, Molon, G, Beltrame, A, Bonfanti, P, Valsecchi, M, Genovesi, S, Maloberti, Alessandro, Giannattasio, Cristina, Rebora, Paola, Occhino, Giuseppe, Ughi, Nicola, Biolcati, Marco, Gualini, Elena, Rizzi, Jacopo Giulio, Algeri, Michela, Giani, Valentina, Rossetti, Claudio, Epis, Oscar Massimiliano, Molon, Giulio, Beltrame, Anna, Bonfanti, Paolo, Valsecchi, Maria Grazia, and Genovesi, Simonetta
- Abstract
Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in C
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- 2022
30. Impact of Treosulfan Exposure on Early and Long-Term Clinical Outcomes in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Prospective Multicenter Study
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van der Stoep, M. Y. E. C., Bertaina, A., Moes, D. J. A. R., Algeri, M., Bredius, R. G. M., Smiers, F. J. W., Berghuis, D., Buddingh, E. P., Mohseny, A. B., Guchelaar, H. -J., Locatelli, Franco, Zwaveling, J., Lankester, A. C., Locatelli F. (ORCID:0000-0002-7976-3654), van der Stoep, M. Y. E. C., Bertaina, A., Moes, D. J. A. R., Algeri, M., Bredius, R. G. M., Smiers, F. J. W., Berghuis, D., Buddingh, E. P., Mohseny, A. B., Guchelaar, H. -J., Locatelli, Franco, Zwaveling, J., Lankester, A. C., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Treosulfan-based conditioning has gained popularity in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) because of its presumed favorable efficacy and toxicity profile. Treosulfan is used in standardized dosing regimens based on body surface area. The relationships between systemic treosulfan exposure and early and long-term clinical outcomes in pediatric patients undergoing allogeneic HSCT for nonmalignant diseases remain unclear. In this a multicenter, prospective observational study, we assessed the association between treosulfan exposure and early and, in particular, long-term clinical outcomes. Our study cohort comprised 110 pediatric patients with nonmalignant diseases who underwent HSCT between 2011 and 2019 in Leiden, The Netherlands and Rome, Italy. Blood samples were collected, and treosulfan area under the receiver operating characteristic curve (AUC0-∞) was estimated as a measure of exposure. Cox proportional hazard survival analyses were performed to assess the relationships between treosulfan exposure and overall survival (OS) and event-free survival (EFS). The predictive value of systemic treosulfan exposure for the occurrence of toxicity within 28 days was evaluated using a multivariable logistic regression analysis. In the overall cohort, OS and EFS at 2 years were 89.0% and 75.3%, respectively, with an excellent OS of 97% in children age <2 years. The occurrence of grade II-IV acute graft-versus-host disease, the level of 1-year whole blood chimerism, and 2-year OS and EFS were not correlated with treosulfan exposure. The occurrence of skin toxicity (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.26-13.68; P = .02) and all-grade mucositis (OR, 4.43; 95% CI, 1.43-15.50; P = .02), but not grade ≥2 mucositis (OR, 1.51; 95% CI, 0.52 to 4.58; P = .46) was related to high treosulfan exposure (>1750 mg*h/L). Our study demonstrates that standardized treosulfan-based conditioning results in a favorable OS and EFS in infants
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- 2022
31. Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient
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Merli, P., Massa, M., Russo, A., Rea, F., Del Chierico, F., Galaverna, F., Del Bufalo, F., Pane, S., Algeri, M., Romeo, E. F., Masucci, Luca, De Angelis, P., Putignani, L., Locatelli, Franco, Masucci L. (ORCID:0000-0002-8358-6726), Locatelli F. (ORCID:0000-0002-7976-3654), Merli, P., Massa, M., Russo, A., Rea, F., Del Chierico, F., Galaverna, F., Del Bufalo, F., Pane, S., Algeri, M., Romeo, E. F., Masucci, Luca, De Angelis, P., Putignani, L., Locatelli, Franco, Masucci L. (ORCID:0000-0002-8358-6726), and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
NO ABSTRACT AVAILABLE
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- 2022
32. TCRab/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different non malignant disorders
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Merli, P., Pagliara, D., Galaverna, F., Pira, G. L., Andreani, M., Leone, G., Amodio, D., Pinto, R. M., Bertaina, A., Bertaina, V., Mastronuzzi, A., Strocchio, L., Boccieri, E., Pende, D., Falco, M., Nardo, M. D., Del Bufalo, F., Algeri, M., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Merli, P., Pagliara, D., Galaverna, F., Pira, G. L., Andreani, M., Leone, G., Amodio, D., Pinto, R. M., Bertaina, A., Bertaina, V., Mastronuzzi, A., Strocchio, L., Boccieri, E., Pende, D., Falco, M., Nardo, M. D., Del Bufalo, F., Algeri, M., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Several nonmalignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders, or metabolic diseases, lacking a fully matched donor or requiring urgent transplantation underwent TCRab/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study. The median age at transplant was 3.5 years (range 0.3-16.1); the median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (eg, aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/ recent infections at the time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade 1-2 acute GVHD was 14.4% (no patient developed grade 3-4 acute GVHD). Only one patient at risk developed mild chronic GVHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRab/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment of children with NMDs. Prompt donor availability, low incidence of GVHD, and TRM make this strategy an attractive option in NMDs patients. The study is registered at ClinicalTrial.gov as NCT01810120.
- Published
- 2022
33. Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study
- Author
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Ghorashian, S., Jacoby, E., De Moerloose, B., Rives, S., Bonney, D., Shenton, G., Bader, P., Bodmer, N., Quintana, A. M., Herrero, B., Algeri, M., Locatelli, Franco, Vettenranta, K., Gonzalez, B., Attarbaschi, A., Harris, S., Bourquin, J. P., Baruchel, A., Locatelli F. (ORCID:0000-0002-7976-3654), Ghorashian, S., Jacoby, E., De Moerloose, B., Rives, S., Bonney, D., Shenton, G., Bader, P., Bodmer, N., Quintana, A. M., Herrero, B., Algeri, M., Locatelli, Franco, Vettenranta, K., Gonzalez, B., Attarbaschi, A., Harris, S., Bourquin, J. P., Baruchel, A., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: Children aged younger than 3 years were excluded from the ELIANA phase 2 trial of tisagenlecleucel in children with acute lymphoblastic leukaemia. The feasibility, safety, and activity of tisagenlecleucel have not been defined in this group, the majority of whom have high-risk (KMT2A-rearranged) infant acute lymphoblastic leukaemia and historically poor outcomes despite intensification of chemotherapy, and for whom novel therapies are urgently needed. We aimed to provide real-world outcome analysis of the feasibility, activity, and safety of tisagenlecleucel in younger children and infants with acute lymphoblastic leukaemia. Methods: We did an international, multicentre, retrospective cohort study at 15 hospitals across ten countries in Europe. Eligible patients were children aged younger than 3 years at screening between Sept 1, 2018, and Sept 1, 2021, who were screened for tisagenlecleucel therapy for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia according to licensed indications. Patients received a single intravenous infusion of tisagenlecleucel. We tracked chimeric antigen receptor T-cell therapy outcomes using a standardised data reporting form. Overall survival, event-free survival, stringent event-free survival, B-cell aplasia, and toxicity were assessed in all patients who received a tisagenlecleucel infusion. Findings: 38 eligible patients were screened, of whom 35 (92%) received a tisagenlecleucel infusion. 29 (76%) of 38 patients had KMT2A-rearranged acute lymphoblastic leukaemia, and 25 (66%) had relapsed after previous allogeneic haematopoietic stem-cell transplantation (HSCT). Patients had previously received a median of 2 lines (IQR 2–3) of (non-HSCT) therapy. Seven (18%) of 38 patients had received inotuzumab and 14 (37%) had received blinatumomab. After a median of 14 months (IQR 9–21) of follow-up, overall survival at 12 months after tisagenlecleucel infusion was 84% (64–93; five patients had died), event-free s
- Published
- 2022
34. Atrial Fibrillation Incidence in SARS-COV-2 Infected Patients: Predictors and Relationship with in-Hospital Mortality
- Author
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Maloberti, A, Giannattasio, C, Rebora, P, Occhino, G, Ughi, N, Rizzo, J, Fabbri, S, Leidi, F, Cartella, I, Algeri, M, Scarpellini, S, Rossetti, C, Epis, O, Molon, G, Bonfanti, P, Valsecchi, M, Genovesi, S, Maloberti, Alessandro, Giannattasio, Cristina, Rebora, Paola, Occhino, Giuseppe, Ughi, Nicola, Rizzo, Jacopo, Fabbri, Saverio, Leidi, Filippo, Cartella, Iside, Algeri, Michela, Scarpellini, Sara, Rossetti, Claudio, Epis, Oscar, Molon, Giulio, Bonfanti, Paolo, Valsecchi, Maria Grazia, Genovesi, Simonetta, Maloberti, A, Giannattasio, C, Rebora, P, Occhino, G, Ughi, N, Rizzo, J, Fabbri, S, Leidi, F, Cartella, I, Algeri, M, Scarpellini, S, Rossetti, C, Epis, O, Molon, G, Bonfanti, P, Valsecchi, M, Genovesi, S, Maloberti, Alessandro, Giannattasio, Cristina, Rebora, Paola, Occhino, Giuseppe, Ughi, Nicola, Rizzo, Jacopo, Fabbri, Saverio, Leidi, Filippo, Cartella, Iside, Algeri, Michela, Scarpellini, Sara, Rossetti, Claudio, Epis, Oscar, Molon, Giulio, Bonfanti, Paolo, Valsecchi, Maria Grazia, and Genovesi, Simonetta
- Abstract
Among the different CardioVascular (CV) manifestation of the COronaVIrus-related Disease (COVID) particular attention has been paid to arrhythmia and particularly to Atrial fibrillation (AF). The aim of our study was to assess the incidence of AF episodes in patients ospitalisat for COVID and to evaluate its predictors and its relationship with in-hospital all-cause mortality.
- Published
- 2022
35. COVID-19 AND CARDIOVASCULAR SYSTEM: NOT ONLY HEART BUT ALSO VASCULAR. THE EFFECTS OF THE INFECTION ON ARTERIAL STIFFNESS
- Author
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Maloberti, A, Gualini, E, Scarpellini, S, Algeri, M, Biolcati, M, Grasso, E, Tognola, C, Moreo, A, Giannattasio, C, Maloberti, A, Gualini, E, Scarpellini, S, Algeri, M, Biolcati, M, Grasso, E, Tognola, C, Moreo, A, and Giannattasio, C
- Published
- 2022
36. Endothelial Dysfunction in Patients with Advanced Heart Failure Treated with Levosimendan Periodic Infusion Compared with Optimal Medical Therapy: A Pilot Study
- Author
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Maloberti, A, Sun, J, Zannoni, J, Occhi, L, Bassi, I, Fabbri, S, Colombo, V, Gualini, E, Algeri, M, Varrenti, M, Masciocco, G, Perna, E, Oliva, F, Cipriani, M, Frigerio, M, Giannattasio, C, Maloberti, Alessandro, Sun, Jinwei, Zannoni, Jessica, Occhi, Lucia, Bassi, Ilaria, Fabbri, Saverio, Colombo, Valentina, Gualini, Elena, Algeri, Michela, Varrenti, Marisa, Masciocco, Gabriella, Perna, Enrico, Oliva, Fabrizio, Cipriani, Manlio, Frigerio, Maria, Giannattasio, Cristina, Maloberti, A, Sun, J, Zannoni, J, Occhi, L, Bassi, I, Fabbri, S, Colombo, V, Gualini, E, Algeri, M, Varrenti, M, Masciocco, G, Perna, E, Oliva, F, Cipriani, M, Frigerio, M, Giannattasio, C, Maloberti, Alessandro, Sun, Jinwei, Zannoni, Jessica, Occhi, Lucia, Bassi, Ilaria, Fabbri, Saverio, Colombo, Valentina, Gualini, Elena, Algeri, Michela, Varrenti, Marisa, Masciocco, Gabriella, Perna, Enrico, Oliva, Fabrizio, Cipriani, Manlio, Frigerio, Maria, and Giannattasio, Cristina
- Abstract
Endothelial dysfunction (ED) is frequently found in patients with heart failure (HF). Among several pharmacological agents reported to improve endothelial function, levosimendan seems to be a promising one, even though, to date, only two previously published studies have evaluated its effects on ED in these patients. The aim of our pilot study was to further investigate the role of periodic levosimendan infusion on endothelial function in patients affected by advanced HF. In this cross-sectional study, three different groups were enrolled: 20 patients with advanced HF treated with periodic levosimendan (LEVO), 20 patients with HF on optimal medical therapy (OMT), and 20 healthy subjects (control group). ED was evaluated through flow-mediated dilation (FMD) at the level of the brachial artery. The three groups presented similar ages with significant differences in gender distribution, systolic blood pressure, and chronic kidney disease (eGFR < 30 mL/min). In HF patients, ischaemic aetiology was more prevalent in the LEVO group than in the OMT group (60 vs. 40%, p < 0.001). The New York Heart Association (NYHA) functional class was worse in the LEVO group, as well as in NT-proBNP (5636.7 ± 6164.6 ng/dL and 1243.7 ± 1487.2 ng/dL, in the LEVO and OMT groups, respectively, p = 0.005). The FMD was significantly higher in the healthy control group compared to that of the OMT group (15.7 ± 6.4 vs. 9.1 ± 6.0%, p = 0.007) while it showed an intermediate value in LEVO patients (12.4 ± 7.1%) (ANOVA p = 0.010). In conclusion, levosimendan therapy seems to ameliorate endothelial dysfunction related to heart failure. Longitudinal studies in patients on periodic therapy are needed in order to confirm the long-term effects of levosimendan on ED.
- Published
- 2022
37. HLA-haploidentical TCRab1/CD191-depleted stem cell transplantation in children and young adults with Fanconi anemia
- Author
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Strocchio, L., Pagliara, D., Algeri, M., Pira, G. L., Rossi, F., Bertaina, V., Leone, G., Pinto, R. M., Andreani, M., Agolini, E., Girardi, K., Gaspari, S., Grapulin, L., Bufalo, F. D., Novelli, A., Merli, P., and Locatelli, Franco
- Subjects
HLA-haploidentical tranpslant ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA - Published
- 2021
38. The role of allogeneic hematopoietic stem cell transplantation in pediatric leukemia
- Author
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Algeri, M., Merli, P., Locatelli, Franco, Pagliara, D., Locatelli F. (ORCID:0000-0002-7976-3654), Algeri, M., Merli, P., Locatelli, Franco, Pagliara, D., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for many children with high-risk or relapsed acute leukemia (AL), thanks to the combination of intense preparative radio/chemotherapy and the graft-versus-leukemia (GvL) effect. Over the years, progress in high-resolution donor typing, choice of conditioning regimen, graft-versus-host disease (GvHD) prophylaxis and supportive care measures have continuously improved overall transplant outcome, and recent successes using alternative donors have extended the potential application of allotransplantation to most patients. In addition, the importance of minimal residual disease (MRD) before and after transplantation is being increasingly clarified and MRD-directed interventions may be employed to further ameliorate leukemia-free survival after allogeneic HSCT. These advances have occurred in parallel with continuous refinements in chemotherapy protocols and the development of targeted therapies, which may redefine the indications for HSCT in the coming years. This review discusses the role of HSCT in childhood AL by analysing transplant indications in both acute lymphoblastic and acute myeloid leukemia, together with current and most promising strategies to further improve transplant outcome, including optimization of conditioning regimen and MRD-directed interventions.
- Published
- 2021
39. Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts
- Author
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Quintarelli, C., Guercio, M., Manni, S., Boffa, I., Sinibaldi, M., DI Cecca, S., Caruso, S., Abbaszadeh, Z., Camera, A., Cembrola, B., Ciccone, R., Orfao, A., Martin-Martin, L., Gutierrez-Herrero, S., Herrero-Garcia, M., Cazzaniga, G., Nunes, V., Songia, S., Marcatili, P., Marin, F. I., Ruella, M., Bertaina, V., Vinti, L., Del Bufalo, F., Algeri, M., Merli, P., De Angelis, B., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Quintarelli, C., Guercio, M., Manni, S., Boffa, I., Sinibaldi, M., DI Cecca, S., Caruso, S., Abbaszadeh, Z., Camera, A., Cembrola, B., Ciccone, R., Orfao, A., Martin-Martin, L., Gutierrez-Herrero, S., Herrero-Garcia, M., Cazzaniga, G., Nunes, V., Songia, S., Marcatili, P., Marin, F. I., Ruella, M., Bertaina, V., Vinti, L., Del Bufalo, F., Algeri, M., Merli, P., De Angelis, B., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk of CD19-/CAR+ leukemic relapse due to inadvertent transduction of leukemia cells. BackgroundMethods We evaluated the impact of a high percentage of leukemia blast contamination in patient-derived starting material (SM) on CAR T-cell drug product (DP) manufacturing. In vitro as well as in vivo models were employed to identify characteristics of the construct associated with better profile of safety in case of inadvertent B-cell leukemia transduction during CAR T-cell manufacturing. Results The presence of large amounts of CD19+ cells in SM did not affect the transduction level of DPs, as well as the CAR T-cell rate of expansion at the end of standard production of 14 days. DPs were deeply characterized by flow cytometry and molecular biology for Ig-rearrangements, showing that the level of B-cell contamination in DPs did not correlate with the percentage of CD19+ cells in SM, in the studied patient cohort. Moreover, we investigated whether CAR design may affect the control of CAR+ leukemia cells. We provided evidences that CAR.CD19 short linker (SL) prevents complete epitope masking in CD19+CAR+ leukemia cells and we demonstrated in vitro and in vivo that CD19 +CAR(SL)+leukemic cells are killed by CAR.CD19 T-cells. Conclusions Taken together, these data suggest that a VL-VH SL may result in a safe CAR-T product, even when manufacturing starts from biological materials characterized by heavy contamination of leukemia blasts.
- Published
- 2021
40. Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies
- Author
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Guercio, M., Manni, S., Boffa, I., Caruso, S., Di Cecca, S., Sinibaldi, M., Abbaszadeh, Z., Camera, A., Ciccone, R., Polito, V. A., Ferrandino, F., Reddel, S., Catanoso, M. L., Bocceri, E., Del Bufalo, F., Algeri, M., De Angelis, B., Quintarelli, C., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Guercio, M., Manni, S., Boffa, I., Caruso, S., Di Cecca, S., Sinibaldi, M., Abbaszadeh, Z., Camera, A., Ciccone, R., Polito, V. A., Ferrandino, F., Reddel, S., Catanoso, M. L., Bocceri, E., Del Bufalo, F., Algeri, M., De Angelis, B., Quintarelli, C., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
T cells engineered with chimeric antigen receptor (CAR-T cells) are an effective treatment in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia or B-cell non-Hodgkin lymphoma. Despite the reported exciting clinical results, the CAR-T cell approach needs efforts to improve the safety profile, limiting the occurrence of adverse events in patients given this treatment. Besides the most common side effects, such as cytokine release syndrome and CAR-T cell–related encephalopathy syndrome, another potential issue involves the inadvertent transduction of leukemia B cells with the CAR construct during the manufacturing process, thus leading to the possibility of a peculiar mechanism of antigen masking and treatment resistance. In this study, we investigated whether the inclusion of the inducible caspase 9 (iC9) suicide gene in the CAR construct design could be an effective safety switch to control malignant CAR+ B cells, ultimately counteracting this serious adverse event. iC9 is a suicide gene able to be activated through binding with an otherwise inert small biomolecule, known as AP1903. The exposure of iC9.CAR.CD19-DAUDI lymphoma and iC9.CAR.CD19-NALM-6 leukemia cells in vitro to 20 nM of AP1903 resulted into the prompt elimination of CAR+ B-leukemia/lymphoma cell lines. The results obtained in the animal model corroborate in vitro data, since iC9.CAR.CD19+ tumor cells were controlled in vivo by the activation of the suicide gene through administration of AP1903. Altogether, our data indicate that the inclusion of the iC9 suicide gene may result in a safe CAR-T cell product, even when manufacturing starts from biological materials characterized by heavy leukemia blast contamination.
- Published
- 2021
41. Use of ruxolitinib to control graft-versus-host–like disease in Omenn syndrome and successfully bridging to HSCT
- Author
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Grasso, A. G., Del Bufalo, F., Boccieri, E., Russo, A. F., Carta, R., Algeri, M., Lombardo, M., Pagliara, D., Corsetti, T., Locatelli, Franco, Merli, P., Locatelli F. (ORCID:0000-0002-7976-3654), Grasso, A. G., Del Bufalo, F., Boccieri, E., Russo, A. F., Carta, R., Algeri, M., Lombardo, M., Pagliara, D., Corsetti, T., Locatelli, Franco, Merli, P., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
NO ABSTRACT
- Published
- 2021
42. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia
- Author
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Quintarelli, C., Sivori, S., Caruso, S., Carlomagno, S., Falco, M., Boffa, I., Orlando, D., Guercio, M., Abbaszadeh, Z., Sinibaldi, M., Di Cecca, S., Camera, A., Cembrola, B., Pitisci, A., Andreani, M., Vinti, L., Gattari, S., Del Bufalo, F., Algeri, M., Li Pira, G., Moseley, A., De Angelis, B., Moretta, L., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Quintarelli, C., Sivori, S., Caruso, S., Carlomagno, S., Falco, M., Boffa, I., Orlando, D., Guercio, M., Abbaszadeh, Z., Sinibaldi, M., Di Cecca, S., Camera, A., Cembrola, B., Pitisci, A., Andreani, M., Vinti, L., Gattari, S., Del Bufalo, F., Algeri, M., Li Pira, G., Moseley, A., De Angelis, B., Moretta, L., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective “off-the-shelf” immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.
- Published
- 2020
43. Gata2 related conditions and predisposition to pediatric myelodysplastic syndromes
- Author
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Bruzzese, A., Leardini, D., Masetti, R., Strocchio, L., Girardi, K., Algeri, M., Del Baldo, G., Locatelli, Franco, Mastronuzzi, A., Locatelli F. (ORCID:0000-0002-7976-3654), Bruzzese, A., Leardini, D., Masetti, R., Strocchio, L., Girardi, K., Algeri, M., Del Baldo, G., Locatelli, Franco, Mastronuzzi, A., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Myelodysplastic syndromes (MDS) are hematopoietic disorders rare in childhood, often occurring in patients with inherited bone marrow failure syndromes or germinal predisposition syndromes. Among the latter, one of the most frequent involves the gene GATA binding protein 2 (GATA2), coding for a transcriptional regulator of hematopoiesis. The genetic lesion as well as the clinical phenotype are extremely variable; many patients present hematological malignancies, especially MDS with the possibility to evolve into acute myeloid leukemia. Variable immune dysfunction, especially resulting in B-and NK-cell lymphopenia, lead to severe infections, including generalized warts and mycobacterial infection. Defects of alveolar macrophages lead to pulmonary alveolar proteinosis through inadequate clearance of surfactant proteins. Currently, there are no clear guidelines for the monitoring and treatment of patients with GATA2 mutations. In patients with MDS, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT) that restores normal hematopoiesis preventing the progression to acute myeloid leukemia and clears long-standing infections. However, to date, the donor type, conditioning regimen, and the optimal time to proceed to HSCT, as well as the level of chimerism needed to reverse the phenotype, remain unclear highlighting the need for consensus guidelines.
- Published
- 2020
44. Cord blood transplantation for acute leukemia
- Author
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Algeri, M., Gaspari, S., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Algeri, M., Gaspari, S., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Introduction: Umbilical cord blood transplantation (UCBT) is a suitable alternative for patients with acute leukemia (AL) in need of an allograft and who lack an HLA-matched donor. Single-institution and registry studies have shown that, in both children and adults with AL, the outcome of UCBT is comparable to that of matched unrelated donor. At the same time, these studies have highlighted some limitations of UCBT, such as increased early mortality and delayed recovery of both hematopoietic and immune compartment, which hamper a more widespread adoption of this approach. Areas covered: In this review, we will analyze the current results of UCBT in children and adults with AL, including comparisons with other hematopoietic stem cell sources and transplant strategies. We will also discuss important factors to be considered when selecting UCB units, as well as future strategies to further improve the outcome of UCBT recipients. Expert opinion: The utilization of UCBT for the treatment of AL patients has decreased in recent years. However, recent clinical data suggesting that UCBT might offer better results in patients with minimal residual disease, as well as innovative strategies to facilitate engraftment, reduce transplant-related mortality, and optimize anti-leukemic activity, may pave the way toward a second youth for use of UCB cells.
- Published
- 2020
45. Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: Gut microbiota profiling, infectious and clinical outcomes
- Author
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Merli, P., Putignani, L., Ruggeri, A., Del Chierico, F., Gargiullo, L., Galaverna, F., Gaspari, S., Pagliara, D., Russo, A., Pane, S., Strocchio, L., Algeri, M., Rea, F., Romeo, E. F., Bernaschi, P., Muda, A. O., Dallapiccola, B., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Merli, P., Putignani, L., Ruggeri, A., Del Chierico, F., Gargiullo, L., Galaverna, F., Gaspari, S., Pagliara, D., Russo, A., Pane, S., Strocchio, L., Algeri, M., Rea, F., Romeo, E. F., Bernaschi, P., Muda, A. O., Dallapiccola, B., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
NO ABSTRACT
- Published
- 2020
46. Successful muscle regeneration by a homologous microperforated scaffold seeded with autologous mesenchymal stromal cells in a porcine esophageal substitution model
- Author
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Marzaro, M., Algeri, M., Tomao, L., Tedesco, S., Caldaro, Tamara, Balassone, Valerio, Contini, A. C., Guerra, L., Federici D'Abriola, G., Francalanci, P., Caristo, Maria Emiliana, Lupoi, L., Boskoski, Ivo, Bozza, Alessandro, Astori, G., Pozzato, G., Pozzato, A., Costamagna, Guido, Dall'Oglio, Luigi, Caldaro T., Balassone V., Caristo M. E., Boskoski I. (ORCID:0000-0001-8194-2670), Bozza A., Costamagna G. (ORCID:0000-0002-8100-2731), Dall'Oglio L., Marzaro, M., Algeri, M., Tomao, L., Tedesco, S., Caldaro, Tamara, Balassone, Valerio, Contini, A. C., Guerra, L., Federici D'Abriola, G., Francalanci, P., Caristo, Maria Emiliana, Lupoi, L., Boskoski, Ivo, Bozza, Alessandro, Astori, G., Pozzato, G., Pozzato, A., Costamagna, Guido, Dall'Oglio, Luigi, Caldaro T., Balassone V., Caristo M. E., Boskoski I. (ORCID:0000-0001-8194-2670), Bozza A., Costamagna G. (ORCID:0000-0002-8100-2731), and Dall'Oglio L.
- Abstract
Background: Since the esophagus has no redundancy, congenital and acquired esophageal diseases often require esophageal substitution, with complicated surgery and intestinal or gastric transposition. Peri-and-post-operative complications are frequent, with major problems related to the food transit and reflux. During the last years tissue engineering products became an interesting therapeutic alternative for esophageal replacement, since they could mimic the organ structure and potentially help to restore the native functions and physiology. The use of acellular matrices pre-seeded with cells showed promising results for esophageal replacement approaches, but cell homing and adhesion to the scaffold remain an important issue and were investigated. Methods: A porcine esophageal substitute constituted of a decellularized scaffold seeded with autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) was developed. In order to improve cell seeding and distribution throughout the scaffolds, they were micro-perforated by Quantum Molecular Resonance (QMR) technology (Telea Electronic Engineering). Results: The treatment created a microporous network and cells were able to colonize both outer and inner layers of the scaffolds. Non seeded (NSS) and BM-MSCs seeded scaffolds (SS) were implanted on the thoracic esophagus of 4 and 8 pigs respectively, substituting only the muscle layer in a mucosal sparing technique. After 3 months from surgery, we observed an esophageal substenosis in 2/4 NSS pigs and in 6/8 SS pigs and a non-practicable stricture in 1/4 NSS pigs and 2/8 SS pigs. All the animals exhibited a normal weight increase, except one case in the SS group. Actin and desmin staining of the post-implant scaffolds evidenced the regeneration of a muscular layer from one anastomosis to another in the SS group but not in the NSS one. Conclusions: A muscle esophageal substitute starting from a porcine scaffold was developed and it was fully repopulated by BM-MSCs after
- Published
- 2020
47. Female sexuality and vaginal health across the menopausal age
- Author
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Angelo, Cagnacci, Martina, Venier, Anjeza, Xholli, Chiara, Paglietti, Salvatore, Caruso, for the ANGEL Study Group: Algeri, M, Donvito, G, Bastianelli, C, Cagnacci, A, Palma, F, Napolitano, A, Capobianco, G, Dessole, S, Cianci, A, Caruso, S, Cinque, B, Dati, S, Cioffi, Gp, Costantino, D, D’Anna, R, De Leo, V, Di Carlo, C, Di Francesco, A, Di Renzo, G, Baldoni, A, Lorefice, R, Ferrazzi, E, Valente, I, Gambacciani, M, Gambera, A, Greco, P, Bonaccorsi, G, Guaschino, S, Tredici, Z, Labanchi, R, Chiacchio, A, Lanzone, A, Villa, P, Lello, S, Capozzi, A, Leo, L, Salvatores, M, Marchesoni, D, Vogrig, E, Perrone, A, Segatore, M, Pallone, B, Petruzzelli, F, Libergoli, A, Roccamorena, A, Scarciglia, M, Serracchioli, R, Meriggiola, C, Surico, N, Zorzeti Cigna, S, Zullo, F, Delfini, R, and Giovannini, P
- Subjects
Adult ,medicine.medical_specialty ,Cross-sectional study ,General Mathematics ,media_common.quotation_subject ,Vaginal Diseases ,030209 endocrinology & metabolism ,Human sexuality ,Orgasm ,NO ,03 medical and health sciences ,0302 clinical medicine ,Atrophy ,FSFI ,Menopause ,Perimenopause ,Sexuality ,Vaginal atrophy ,Vaginal dryness ,Sexuality, FSFI, Vaginal atrophy, Vaginal dryness, Menopause, Perimenopause ,medicine ,Prevalence ,Humans ,media_common ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Applied Mathematics ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Sexual Dysfunction, Physiological ,Sexual dysfunction ,Cross-Sectional Studies ,Dyspareunia ,Multicenter study ,Italy ,Vagina ,FSFI, Menopause, Perimenopause, Sexuality, Vaginal atrophy, Vaginal dryness ,Observational study ,Female ,medicine.symptom ,business - Abstract
The primary aim was to evaluate changes in female sexuality across the menopausal period, and the secondary objective was to test the associations of female sexuality domains with vaginal atrophy and its symptoms.A cross-sectional multicenter study was performed involving 518 women, 40 to 55 years of age, consulting outpatient gynecological services at 30 centers across Italy. Vaginal atrophy was identified by the contemporaneous presence of a pH5, subjective vaginal dryness, and an objective sign. The relationships between vaginal atrophy and its main symptoms (vaginal dryness and dyspareunia), and Female Sexual Function Index (FSFI) score and its domains (desire, arousal, orgasm, dyspareunia, lubrication, and sexual satisfaction) were analyzed.The prevalence of sexual dysfunction, as defined by a FSFI score26.55, was 70.6%, increasing from 55% in the years 40 to 45, to 82.8% (P 0.01) in the years 52 to 55 of age. Mean FSFI score decreased from 40 to 45, to 46 to 48 years of age (23.13 ± 9.76 vs 19.49 ± 9.88; P 0.05), and from 48 to 51, to 52 to 55 years of age (21.3 ± 8.06 to 17.59 ± 9.11; P 0.01). Independent determinants of FSFI were age, vaginal atrophy, and the presence of vaginal dryness and dyspareunia (R2 0.208; P = 0.011). FSFI score was independently correlated (R2 0.116) with weight (CR -0.067; 95% confidence interval [CI] -0.126, -0.006; P 0.032), menopausal status (CR -2.406; 95% CI -4.180, -0.63; P 0.008), and vaginal dryness (CR -5.647; 95% CI -7.677, -3.618; P 0.0001). Vaginal dryness was the only variable correlated independently with each FSFI domain, including desire (also correlated with menopausal status), arousal (with age and menopausal status), lubrication (with age), orgasm (with age), satisfaction (with vaginal atrophy and being an ex-smoker), and dyspareunia (with age and spontaneously referred dyspareunia).In the perimenopausal years, FSFI score decreases and sexual dysfunction increases by about 30%. Vaginal dryness is the symptom of vaginal atrophy most closely related to all domains of female sexuality.
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- 2019
48. Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia
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Quintarelli, C., primary, Sivori, S., additional, Caruso, S., additional, Carlomagno, S., additional, Falco, M., additional, Boffa, I., additional, Orlando, D., additional, Guercio, M., additional, Abbaszadeh, Z., additional, Sinibaldi, M., additional, Di Cecca, S., additional, Camera, A., additional, Cembrola, B., additional, Pitisci, A., additional, Andreani, M., additional, Vinti, L., additional, Gattari, S., additional, Del Bufalo, F., additional, Algeri, M., additional, Li Pira, G., additional, Moseley, A., additional, De Angelis, B., additional, Moretta, L., additional, and Locatelli, F., additional
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- 2019
- Full Text
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49. T-cell depleted HLA-haploidentical HSCT in a child with neuromyelitis optica
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Ceglie, G., Papetti, L., Figa Talamanca, L., Lucarelli, B., Algeri, M., Gaspari, S., Li Pira, G., Colafati, G. -S., Montanari, M., Valeriani, M., Locatelli, Franco, Merli, P., Locatelli F. (ORCID:0000-0002-7976-3654), Ceglie, G., Papetti, L., Figa Talamanca, L., Lucarelli, B., Algeri, M., Gaspari, S., Li Pira, G., Colafati, G. -S., Montanari, M., Valeriani, M., Locatelli, Franco, Merli, P., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Neuromyelitis optica is an immune-mediated disease characterized by a relapsing course, resulting in progressive disability. In children, given the long life expectancy, a disease-modifying treatment could be particularly desirable. Unfortunately, the currently available treatment strategies with this potential are scarce. Very limited data are available about the use of allogeneic hematopoietic stem cell transplantation (HSCT) for autoimmune neurological diseases. In this report, we present a pediatric case successfully treated with allogeneic HSCT from an HLA-haploidentical donor, after ex vivo TCR/CD19-depletion of the graft. To the best of our knowledge, this is the first case of a pediatric patient to benefit from such a treatment.
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- 2019
50. Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia
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Merli, P., Algeri, M., Del Bufalo, F., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Merli, P., Algeri, M., Del Bufalo, F., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Purpose of Review: The remarkable improvement in the prognosis of children with acute lymphoblastic leukemia (ALL) has been mainly achieved through the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). This paper reviews the current indications to HSCT in ALL children, as well as the type of donor and conditioning regimens commonly used. Finally, it will focus on future challenges in immunotherapy. Recent Findings: As our comprehension of disease-specific risk factors improves, indications to HSCT continue to evolve. Future studies will answer the year-old question on the best conditioning regimen to be used in this setting, while a recent randomized controlled study fixed the optimal anti-thymocyte globulin dose in unrelated donor HSCT. Summary: HSCT, the oldest immunotherapy used in clinical practice, still represents the gold standard consolidation treatment for a number of pediatric patients with high-risk/relapsed ALL. New immunotherapies hold the promise of further improving outcomes in this setting.
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- 2019
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