La potenziale applicazione del trapianto allogenico secondo una politica allargata della ricerca del donatore: analisi di intenzione al trattamento effettuata presso il Rome Transplant Network

Rome Transplant Network (RTN), fondato nell'aprile 2006, rappresenta un Programma Unico di Trapianto Metropolitano che coinvolge sette centri trapianto. La politica del RTN è quella di individuare, per i pazienti privi di un donatore familiare HLA identico e candidati ad un trapianto allogenico, una fonte alternativa di Cellule Staminali Ematopoietiche (HSC) attraverso la simultanea ricerca che, oltre allo studio di donatori e di unità di sangue di cordone ombelicale, prende in considerazione in caso di mancata disponibilità di donatore MUD/unità SCO o di condizioni di urgenza clinica del paziente, la possibilità di utilizzare il donatore familiare mismatched.(HRD) Lo scopo dello studio è l'identificazione di un donatore idoneo al fine di eseguire il trapianto in tempi adeguati. I dati sono stati ottenuti dal database del RTN. I criteri di selezione per il Donatore Volontario da Registro (MUD) consistono in 8/10 loci HLA compatibili, testati in bassa risoluzione per HLA di classe I ed in alta risoluzione (HR) per la classe II. I criteri di selezione per le singole unità di Sangue di Cordone Ombelicale (SCO) sono basati su dosi cellulari: TNC > 3x107/kg e CD34+ > 1x105/kg e su un grado di compatibilità > 4/6 antigeni HLA. In questo lavoro, riportiamo i risultati dell’analisi “intention to treat” (ITT) sul potenziale impatto terapeutico della nostra politica di trapianto. Dall’aprile 2006 al dicembre 2010, 428 su 462 pazienti candidati sono stati considerati idonei a ricevere un trapianto allogenico. Un donatore familiare HLA identico è stato trovato in 146 su 428 (34%) casi, mentre la ricerca di un donatore alternativo è stata attivata per 282 (66%) pazienti. Tredici pazienti si trovavano ad uno stadio troppo precoce della ricerca per essere valutati; in 25 (9%) dei rimanenti 269 (95%) pazienti non è stato possibile identificare un donatore alternativo poiché il 40%, affetto da emoglobinopatie, richiedeva criteri di corrispondenza HLA più stringenti. Un donatore alternativo è stato identificato per 244 (91%) di questi 269 pazienti. Nonostante l'identificazione di un donatore alternativo, durante il processo di ricerca 51 pazienti (20%) hanno perduto l'idoneità al trapianto per diverse cause. Ad oggi, 193 (80%) dei 244 pazienti sono stati effettivamente trapiantati (50 SCO, 73 MUD; 54 HRD, 16 ancora non trapiantati ma programmati), mentre 146 pazienti sono stati sottoposti a trapianto da donatore familiare HLA identico . In conclusione, un donatore compatibile è stato identificato per 390 (91%) dei 428 pazienti ritenuti idonei al trapianto allogenico e successivamente 339 (80%) di questi sono stati sottoposti a trapianto. Dall’analisi ITT, possiamo concludere che, adottando la politica del RTN nel condurre la ricerca a 360 gradi includendo tutte le tipologie di donatore alternativo, si offre la possibilità a tutti i pazienti considerati candidabili alla procedura di poter effettivamente essere sottoposti al trapianto allogenico.Rome Transplant Network (RTN), founded in April 2006, represents a Metropolitan Transplant Program involving seven transplant centers. The policy of RTN for patients (pts) lacking of a HLA identical sibling and candidate to an allogeneic hematopoietic stem cell transplant (HSCT) is the contemporary search for an alternative HSC source such as Matched Unreleted Donor (MUD), Cord Blood (CB) or Haploidentical Related Donor (HRD). The aim of the study is the identification of a suitable donor in order to perform transplant procedure in adequate timing. Data were obtained from RTN database. The selection criteria for MUD consist of a 8/10 HLA loci matching tested at low resolution for class I HLA and at high resolution (HR) for class II. Selection criteria for single CB unit are based on cell doses TNC > 3x107 / kg and CD34+ > 1x 105 / kg and on a > 4/6 HLA antigen compatibility. From April 2006, the haploidentical option was also simultaneously considered, so all closer family members have been tested for the HLA. Mother was considered as 1st choice. Here, we report the results of the intention to treat (ITT) analysis on the potential therapeutic impact of our transplant policy. From April 2006 to December 2010, 428 out of 462 candidate pts have been considered eligible to receive an allogeneic HSCT for hematological desease. HLA identical sibling donor was available in 146 out of 428 (34%) cases, while a search process for an alternative donor was activated for 282 (66%) pts. 13 pts are too early to be evaluated and we were not able to identify any alternative donor for 25 (9%) of the 269 (95%) remaining pts because of 40%, affected by Haemoglobinopathies, requiring more restricted HLA matching criteria. An alternative donor was identified for 244 (91%) of these 269 pts. Despite the identification of an alternative donor, 51 (20%) pts lost the eligibility during the search process because of several causes. To date, 193 (80%) of 244 pts have been definitively transplanted (50 CB; 73 MUD; 54 HRD) or are willing to proceed towards the transplant (n = 16), while 146 pts have been grafted from a HLA identical siblings. In summary, a suitable donor was identified for 390 (91%) of 428 pts eligible for an allogeneic transplant which could be performed in 339 (80%) of them. From this ITT analysis, we can conclude that, by adopting the RTN policy of widespread donor search and multiple transplant options, the allogeneic transplant can be offered as a potential therapeutic procedure to a large majority of pts

Effects of carbon nanotubes on human monocytes.

Carbon nanotubes are considered to be one of the novel most attractive materials in nanotechnology. Because of their multiple industrial and biomedical applications, thorough studies on their toxicity and biocompatibility become a priority in order to prevent possible health risks. In this study the effects of multiwalled carbon nanotubes (MWCNT) on healthy monocytes from human peripheral blood were investigated. The results indicate that MWCNT exert a cytotoxic effect on monocytes, inducing cell death and increasing the extent of apoptosis induced by a chemotherapic agent. This cytotoxic effect may have important implications, and much attention in terms of evaluation of exposure risks is recommended

Effect of different carbon nanotubes on cell viability and proliferation

Carbon nanotubes ( CNTs) are a focus of intense research for their potential applications in multiple diverse applications, including innovative biomedical applications. Due to their very recent discovery, little information is available about the biocompatibility and toxicity of this new class of nanoparticle, and a systematic study on biological interference is lacking. Thus, we decided to explore the toxicity of three different types of carbon nanotube, differing in preparation ( arc discharge versus catalysed chemical vapour deposition); size ( 10 - 50 versus 100 - 150 nm wide x 1 - 10 mu m long); contaminants ( amorphous C, graphite, fullerenes or iron) and morphological type ( multi- walled, MW, or single- walled, SW) on human leukemic U937 cells. We found that these carbon nanotubes exert a strong effect on the proliferation of the reporter U937 monocytic cell. However, these CNTs did not significantly affect the cell viability. These results show that CNTs, though not directly exerting a direct cytotoxic effect, are nonetheless able to deeply alter cell behaviour, and thus we recommend thorough analyses to limit health risk due to uncontrolled exposure

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Abstract BACKGROUND: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. METHODS: We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. RESULTS: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01). CONCLUSIONS: Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. CLINICAL TRIALS REGISTRATION: NCT02088840