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  • 1
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1786-1786
    Abstract: The upper age-limit for patients with hematological malignancies eligible for allo-SCT progressed to 70-75 years. As a consequence, an increase of older patients submitted to allo-SCT has been observed worldwide and in Italy as well. This registry-based retrospective study on behalf of GITMO (GITMO AlloEld) describes the transplant activity among elderly patients in Italy, between 2000 and 2017. Thiry GITMO Centers participated to the Study. 2061 allo-SCTS in patients older than 60 years were exported from PROMISE database and 1996 first transplants were analysed. The median age of the patients at transplant was 63,5 years (59,5-77,8). The most commonly transplanted diseases were acute leukemias and myelodisplastic syndromes (67,5%). 28% and 27% of the patients showed a HCT-CI of 1-2 or grater than 3, respectively. The KPS was 100% in 27,2% and 90% in 42,9% of the cases. 32% of the patients received a myeloablative conditioning regimen and 55% of the patients received an in vivo T-cell depletion (either post transplant cyclophosphamide or ATG). With a median follow up of 10,4 years, the OS at 5 years significantly improved during time, moving from 28% between 2000-2005 to 37% between 2012-2017 (p=0,012). This was related to a significant reduction in RI (45% vs 30%, p & lt;0,0001), whereas NRM remained stable over time (33% vs 35%, p=0,5). The following significant differences were observed across the years of the present study: 1) a longer 5 years OS in patients younger than 65 years (34%) vs those older than 70 years (19%) between 2000 and 2011 only (p=0,003) (Figure 1A and 1B); 2) a longer 5 years OS (p & lt;0.001) and a reduced NRM (p=0.02) for HCT-CI 0 vs 1-2 vs & gt;3 between 2000-2011 only (Figure 2A and 2B); 3) a different 5 years OS according to donor type between 2000 and 2011 only (19% for haplo vs 31% for sibling vs 33% for mismatch UD and 38% for MUD; p & lt;0,0001) (Figure 3A and 3B); 4) a reduction in the incidence of extensive cGVHD at 1 year (15,6% between 2000 and 2005 vs 10,3% between 2012 and 2017, p=0,004) (Figure 4). Comparing 2000-2005 vs 2012-2017, the major significant differences of the patients regard: the baseline disease (more AL/MDS: 40% vs 77%; p & lt;0,001); the disease status at SCT (more CR: 29% vs 54%, p & lt;0,0001), the intensity of conditioning (MAC in 14% vs 42%, p & lt;0,001), the use of alkylator-base conditioning regimen (49% vs 91%; p & lt;0,001) and the use of in vivo T-cell depletion (17% vs 43%, p & lt;0,0001). Moreover, the percentage of patients with HCT-CI & gt; 3 moved from 10% to 30% (p & lt;0,001), in parallel with an increase in patients with KPS 100 (10% vs 30%; p & lt;0,001) By multivariate analysis MUD donor or UCB, no response at the time of SCT and male recipient significantly impaired OS, whereas HCT-CI & lt;1, KPS 90-100 and transplant between 2011-2017 significantly improved OS. These retrospective data showed that the transplant procedure for elderly patients became safer and more effective over time, for a reduction of the RI related to a better selection of patients (more acute leukemias in CR) and a better selection of conditionings (more MAC and more alkylators). Nowdays, the HCT-CI score is probably not sufficient for estimate elderly patients probability of OS and NRM. Figure 1 Figure 1. Disclosures Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 2
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4558-4558
    Abstract: The chimerism analysis after allogeneic haematopoietic stem cell transplantation (HSCT) is a useful tool to monitor the engraftment of donor cells and to early predict graft failure or disease relapse. Among several available methods to perform chimerism study, multiplex fluorescent short tandem repeat (STR) analysis represent a sensitive, accurate and reproducible technique. It provide a high rate of discrimination between donor and recipient cells since that fluorescent signal is proportional to the cells number, obtaining a quantitative assessment of chimerism. Aims Evaluation of a possible correlation between basal donor/recipient allelic discrepancies and post-transplant outcome in terms of graft versus host disease (GvHD) development, neutrophil engraftment, relapse, DFS and OS. Methods We enrolled 111 patients (pts) affected by onco-haematological diseases, consecutively submitted to HSCT at our division between February 2005 and December 2012. Pts were 67 males and 44 females with a median age of 51 years (range 14-70). Underlying diseases were: 58 AML, 10 MDS, 16 ALL, 8 CLL, 6 MM, 2 HL, 9 NHL, 1 IMF, 1 MPD. Myeloablative conditioning regimen was used in 26 pts while a reduced conditioning regimen was used for the other 85 pts. Graft was obtained from sibling donor and unrelated donor in 65 and 46 pts, respectively. GvHD prophylaxis was performed with cyclosporine (CSA) and methotrexate in 61 pts, CSA and mycophenolate mofetil in 43 pts and CSA in 7 pts. Donor and recipient allelic status was performed using a multiplex PCR amplification of ten STR loci: Amelogenin alleles X/Y, D3S1358, FGA, D8S1179, D18S51, D13S317, vWA, D21S11, D5S818, D7S820. We evaluated the donor/recipient (D/R) match or mismatch for each locus and the following variables: GvHD development and onset time, time to neutrophil engraftment, relapse, DFS and OS. Statistical analysis was performed by Kaplan Meier analysis using IBM SPSS Statistics 20 Core System. Results Pts with D/R mismatch for D8S1179 locus achieved neutrophil engraftment (ANC 〉 1* 109/L) at a median time of 18 days (CI 95% 17.202-18.798) compared with 21 days (CI 95% 17.328-24.672) of pts with D/R match for the same locus (p=0.007) (Figure 1A). Pts with D/R mismatch for D3S1358 locus developed acute GvHD at a median time of 20 days (CI 95% 15.781-24.219) compared with 29 days (CI 95% 15.421-42.579) of pts with D/R match for the same locus (p=0.031) (Figure 1B). Pts with D/R mismatch for D3S1358 locus showed an OS of 16 months (CI 95% 11.016-20.984) compared with 41 months (CI 95% 25.420-56.580) of pts with D/R match for the same locus (p=0.025) (Figure 1C). Pts with D/R mismatch for D8S1179 locus showed an OS of 16 months (CI 95% 8.528-23.472) compared with 56 months (CI 95% 11.254-78.057) of pts with D/R match for the same locus (p=0.012) (Figure 1D). No relationships were found with relapse, DFS neither for the other loci. Summary Our results highlight that pts who presented a D/R mismatch for D8S1179 locus showed an earlier neutrophil engraftment but a worse OS compared with the others. Moreover, for D3S1358 locus, D/R mismatch was associated with an earlier onset of acute GvHD after HSCT and with a shorter OS than the D/R match ones. Conclusion STRs are highly polymorphic di-, tri- and tetra-nucleotide repeat non-coding sequences, which are interspersed throughout the genome. Whether or not discrepancies between donor and recipient basal allelic status could be considered useful in predicting post-transplant outcome will require validation in a large sample of pts. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 3
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 1253-1253
    Abstract: Abstract 1253 Introduction: Graft-versus-host disease is one of the main complications after allogeneic stem cell transplantation. Recently, some authors focused their attention on the evaluation of proteomic pattern of biologic samples, as saliva and urine, in patients affected by GHVD. The aim of these studies was to identify a highly sensitive and specific marker of GVHD activity, with a predictive and prognostic value. Several authors have investigated the role of fecal calprotectin in patients affected by inflammatory bowel disease. So, level of fecal calprotectin seems to have a proportional correlation to the degree of immune inflammation of the intestinal mucosa. In this respect, we have analyzed the level of fecal calprotectin in patients submitted to allogeneic stem cell transplantation, to find a non invasive and rapid marker of GVHD. Materials and Methods: We enrolled 32 patients affected by onco-hematological disease and submitted consecutively to allogeneic stem cell transplantation between February 2009 and April 2010 in our centre. Patients’ characteristics were: M/F 18/14 with a median age of 49 years (range 17–65); diagnosis were MDS in 6 patients, plasmacellular leukemia in 1 patient, ALL in 2 patients, CLL in 1 patient, AML in 15 patients, NHL in 6 patients, myelofibrosis in 1 patient; 11 patients were in CR, 3 patients in relapse, 3 patients in PD, 3 patients in PR, 6 patients in stable disease and 6 patients have a refractory/resistant disease; a myeloablative conditioning regimen was used in 9 patient while the other 23 patients received a reduced intensity conditioning regimen; 16 patients received a graft from a match-unrelated donor and 16 from a sibling donor; stem cell source were BM in 1 patient, CB in 1 patient and PBSC in 30 pts; 3 pts received GVHD prophylaxis with CSA, 16 with CSA+MMF and 13 with CSA+MTX; 5 patient received also ATG and 2 Campath-H1. We evaluated the level of fecal calprotectin at day +30, +60 and +90 after transplant and at the onset of GVHD. Results: Median time to neutrophil engraftment (PMN 〉 0.5×109/L) was 16 days after stem cell transplantation (range 10–29), while a spontaneous platelet recovery (PLTS 〉 20×109/L) was achieved after a median time of 11 days (range 2–46). One pt did not achieve PLT engraftment for progressive disease. TRM at 100 days 25%: 2 pts died for aGVHD, 2 pts for sepsis, 1 pt for pulmonary aspergillosis and 3 for progression of disease. Fourteen pts developed aGVHD (4 pts grade I-II and 10 pts grade III-IV) and 12 pts developed cGVHD (3 pts limited and 9 pts extensive). Fecal calprotectin median level in the first 100 days after transplantation was significantly higher in the group with aGVHD (median value 226.5mg/kg vs 62mg/kg, Fisher exact's test p=0.0063, RR 2.786, CI 1.199–6.473) and in the group of patients with cGVHD (median value 208mg/kg vs 62mg/kg, Fisher exact's test p= 0.0154, RR 2.708, CI 1.153–6.362). Considering the threshold of 100mg/kg we divided patients in 2 groups ( 〈 and 〉 100mg/kg) and we found a strong correlation between fecal calprotectin level and aGVHD onset (p=0.0076)(see figure 1). Conclusion: Despite the small number of patients in our casistic we propose the determination of fecal calprotectin level as a marker of GVHD activity and as a possible predictive factor of cGVHD onset. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 4
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4601-4601
    Abstract: Background : Allogeneic hemopoietic stem cell transplantation (HSCT) has been widely used in hematologic malignancies for over 4 decades. One important question is the longterm outcome of these patients, in terms of leukemia control and quality of life. Aim of the study. Assess the outcome of patients surviving at least 3000 days post allogeneic HSCT, and identify risk factors for failure. Methods. We used our transplant relational database, in which patients' clinical and laboratory data are prospectively recorded during each outpatient visit or during admission. We identified 673 patients who were seen between 8 and 30 years post-transplant. The median follow up was 17.5 years (range 8.2-36.6), median age was 34 years (range1-65). The diagnosis was AML (n=205), ALL (n=97) CML (n=208), MDS (n=51), Lymphoma (n=45), Myelofibrosis (n=19), other (n=48). The stem cell source was bone marrow (BM)(n= 488), peripheral blood (PB) (n=154), cord blood (CB) (n=31). The disease was in remission (n=553) or in relapse (n=120). Result . The overall actuarial survival at 20 years was 86% (95%CI 83%-89%). The CI of TRM at 20 years was 9.4% and the CI of relapse related death (RRD) was 4.6% . Leading causes of death were second tumours (3.2%), chronic GvHD (2.8%) relapse (2.8%). In univariate analysis negative predictors of survival were the following : severe cGvHD (RR 5.0, p=0.002) compared to n0 cGvHD, the use of PB compared to BM as a stem cells source (RR 2.6, p 〈 0.00001), patients age over 40 (RR 3.1, p 〈 0.0001), donors age over 40 (RR 2.4, p=0.0001), advanced disease (RR 2.0, p=0.005), conditioning without TBI (RR 2.1, p=0.0007). The actuarial survival at 20 years of patients grafted from BM or PB was 89% vs 75% (p 〈 0.0001), with a CI of TRM at 20 years of 7% vs 17% respectively (p=0.001) and a CI of RRD of 3% vs 7% (p=0.008). The actuarial 20 year survival for patients 〈 / 〉 40 years was 91% vs 80% (p 〈 0.0001). Survival according to the severity of cGvHD is shown in Figure 1. Multivariate analysis. In a multivariate Cox analysis, negative predictors of survival, were severe cGvHD (RR 5.0, p=0.0003), patients age over 40 (RR 2.4, p=0.001) , PB grafts versus BM (RR 1.8, p=0.002). Conclusions. Patients surviving 8 years post HSCT have a 9% risk of transplant related death and a 4% risk of relapse related death. Chronic GvHD remains the strongest negative predictor of survival , together with patients age , and PB as a stem cell source. The impact of cGvHD 10-20 years post transplant strongly calls for preventing meaures to be adopted early in the transplant course, and or with a preferential use of BM as a stem cell source. Disclosures Angelucci: Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Participation in DMC; BlueBirdBio: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorp., and CRISPR Therapeutics: Other: Participation in DMC.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 5
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 16 ( 2016-09), p. S79-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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    detail.hit.zdb_id: 2193618-3
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  • 6
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-16)
    Abstract: Acute promyelocytic leukemia is a variant of acute myeloid leukemia characterized by t(15;17) and PML/RAR alfa fusion gene. The discovery of the molecular pathogenesis has led to entitle all-trans retinoic acid (ATRA) as the first targeted therapy for acute leukemia. It is usually associated to anthracycline-based chemotherapy with high response rates, but potential long-term sequelae including therapy-related malignancies have been observed. Arsenic trioxide (ATO) was added to obviate these complications and investigational trials aimed to a new strategy with the incorporation of arsenic trioxide (ATO) into initial therapy instead of chemotherapy in selected patients. ATRA plus ATO without chemotherapy was the first attempt to treat low and intermediate-risk patients with APL. Our study aims to describe a monocentric cohort of patients with newly diagnosed APL effectively treated with ATO plus ATRA underlying its efficacy together with the high grade of tolerability of this association. From January 2009 to December 2019 23 APL patients were diagnosed and treated with ATO plus ATRA regimen: 14 males and 9 females patients with a median age of 45 years (range 18-72), for the majority intermediate risk (15 patients, 65%). The treatment was well tolerated and all patients achieved molecular remission after a median time of 3 months (range 1-6 months). All patients proceeded to consolidation phase as outpatients, they maintained complete molecular response at a median time of 44 months (range 15-127) except for 1 patient. All but one patient are alive and in response at a median follow-up of 48 months (range 9-141) without late effects. ATO plus ATRA regimen shows advantages in comparison to chemotherapy; in fact it allowed to treat patients in which chemotherapy could even not be applicable and it did not show secondary hematological diseases. The association of ATO to ATRA as chemo-free regimen enabled to treat APL even without chemotherapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 7
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-8-31)
    Abstract: The aim of this study was to evaluate the role of WT1 expression after allogeneic stem cell transplantation (alloHSCT) in patients with acute myeloid leukemia (AML). We studied WT1 expression in bone marrow cells from 50 patients in complete remission on day +60 after transplant. WT1 was assessed on unfractionated bone marrow mononuclear cells (MNC) and on CD34+ selected cells (CD34+). A ROC curve analysis identified 800 WT1 copies on CD34+ selected cells, as the best cut-off predicting relapse (AUC 0.842, p=0.0006, 85.7% sensitivity and 81.6% specificity) and 100 copies in MNC (AUC 0.819, p=0.007, 83.3% sensitivity and 88.2% specificity). Using the 800 WT1 copy cut off in CD34+ cells, the 2 year cumulative incidence of relapse was 12% vs 38% (p=0.005), and 2 year survival 88% vs 55% (p=0.02). Using the 100 WT1 copy cut off in unfractionated MNC, the 2 year cumulative incidence of relapse 13% vs 44% (p=0.01) and the 2 year survival 88% vs 55% (p=0.08). In a multivariate Cox analysis WT1 expression in CD34 cells proved to highly predictive of relapse (p=0.004); also WT1 expression on unfractionated cells predicted relapse (p=0.03). In conclusion, day-60 WT1 expression after allogeneic HSCT is a significant predictor of relapse, particularly when tested on CD34+ selected bone marrow cells.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 8
    In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 12 ( 2021-12), p. 3585-3588
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2008023-2
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  • 9
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4881-4881
    Abstract: We report a retrospective analysis of 198 consecutive allogeneic stem cell transplant (HSCT) recipients, who received post transplant cyclophosphamide (PTCY), cyclosporine and mycophenolate mofetile as g raft-versus-host-disease (GVHD) prophylaxis. The donor was either HLA matched (n=78) (siblings -32- or unrelated -46) , or a haploidentical relative (HAPLO) (n=120). End points of the study were acute and chronic GVHD, transplant related mortality (TRM), relapse, disease free survival (DFS) and graft versus host and relapse free survival (GRFS). The two groups were comparable except for an older age (49 vs 56 years) in the haplo-HLA group. The diagnosis was mainly acute leukemia (57%), myelofibrosis (21%) or lymphoma (12%). Conditioning was myeloablative in 77% and 73% respectively (p=0.57). Acute GVHD grade II-IV developed in 10% of the HLA matched transplants vs 27% in the HAPLO group (p=0.005). The latter also had more moderate-to-severe cGVHD (4% vs 23%, p & lt;0.001). The cumulative incidence of transplant related mortality (TRM) at 1 year for the HLA matched vs HAPLO patients, was 10% vs 21% (p=0.04) (Fig.1) , with age over 60 years being the major negative predictor in multivariate analysis. Relapse at 1 year was 24% for HLA matched vs 10% for HAPLO transplants (p=0.051) (Fig.1). Disease free survival (DFS) at 1 year was 65% and 68% in matched and HAPLO patients, respectively (p=0.85) (Fig.1) and GRFS 55% vs 49% (p=0.18). In multivariate analysis, age over 60 years was the strongest predictor of DFS and GRFS (HR 1.73, p=0.03 and HR 1,65, p= 0.02). In conclusion: when using the same triple PTCY based GVHD prophylaxis, HLA matched grafts are associated with significantly less acute and chronic GvHD, if compared with HAPLO grafts. There is a trend for reduced TRM at 1 year, especially in chronic myelo-lymphoproliferative disorders, and a trend for increased relapse, resulting in identical disease free survival. Figure 1 Figure 1. Disclosures Laurenti: Gilead: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 10
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4648-4648
    Abstract: Background. The outcome of allogeneic hemopoietic stem cell transplantation (HSCT) is measured in terms of graft versus host disease (GvHD), non-relapse mortality (NRM) and survival. Days of Hospital stay and number of re-admissions, are important surrogates of outcome, quality of life, and also of costs, but are usually not reported. Aim of the study . Assess the number of days alive and outside the Hospital (DAOH) , together with the frequency of a new re-admission, in the first 100 days after transplant. Patients. We analyzed 212 patients who received an allogeneic HSCT from matched sibling (SIB) (n=64), unrelated donors (UD) (n=74) and family haploidentical donors (HAPLO) (n=74). Median age was 49 years (19-71), disease phase was in remission in 53%; diagnoses was acute leukemia (66%) , MDS (14%) chronic disorders 20%. DAOH. The median DAOH for SIB, HAPLO and UD grafts was 78, 72 and 66 days (p=0.0001). The median DAOH for SIB patients was significantly longer than for UD patients (p=0.00002) and for HAPLO grafts (p=0.0008); the median DAOH for UD and HAPLO patients were comparable (p=0.4). Donor type was the strongest predictor of DAOH , followed by a Sorror score 〉 2 (p=0.04). Re-admission. Fifty four patients, of 185 discharged, required a re-admission for complications. the first cause for readmission was fever of unknown origin (54%), followed by GvHD (18,5% ) ,cystitis (8%) , relapse (7%) and respiratory problems (7%). The only factor predicting re-admission was advanced disease (p=0.01). Patients who were re-admitted to hospital within 100 days had a significantly higher risk of non relapse mortality (NRM) (25%) as compared to patient non re-admitted (5%) irrespective of the cause for re-admission (p=0.0001). In a multivariate analysis re-admission was the strongest predictor of NRM, with a risk ratio of 10.9 (p=0.0002). Days of admission and cost. The average number of days in hospital within 100 days from transplant, was 37,6 for UD, 35,0 for HAPLO and 25,0 for SIBS (p=0.0002). The average cost of admission within 100 days from HSCT, was €69522 for UD, €64715 for HAPLO and €46225 euros for SIBS. Conclusion. HAPLO transplants with PT-CY and UD transplants , have lower numbers of DAOH, as compared to SIB grafts, which implies longer stay in hospital and greater cost. Re-admission to Hospital within 100 days is predicted by disease phase and has a very strong impact on non relapse mortality. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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