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Lydia QN Liew,1 Lawrence SC Law,1 Edwin Seet,2 Fabio Di Piazza,3 Katherine E Liu,4 Ming Ann Sim,1 Vanessa TY Chua,1 Toby N Weingarten,5 Ashish K Khanna,6 Lian Kah Ti1,2 On behalf of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Investigators1National University Hospital, Singapore, Singapore; 2National University of Singapore, Yong Loo Lin School of Medicine, Singapore; 3Medtronic Core Clinical Solutions, Study and Scientific Solutions, Rome, Italy; 4Patient Monitoring Clinical Research, Medtronic, Minneapolis, MN, USA; 5Departments of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; 6Wake Forest School of Medicine, Winston-Salem, North Carolina, US & Outcomes Research Consortium, Cleveland, OH, USACorrespondence: Lian Kah Ti, Yong Loo Lin School of Medicine, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore, Tel +65 6779 5555, Email lian_kah_ti@nuhs.edu.sgPurpose: Postoperative monitoring of respiratory status on general care wards typically consists of intermittent checks of oxyhemoglobin saturation and respiratory rate, allowing substantial unmonitored time for severe opioid induced respiratory depression (RD) to develop unnoticed. Oxygen desaturation index (ODI) can be computed solely by continuous pulse oximetry monitoring. In this post-hoc analysis, we evaluate whether nocturnal ODI correlates with RD.Patients and Methods: The PRODIGY trial (NCT02811302) was a multinational study conducted where adult patients receiving parenteral opioids on the general care floor were continuously monitored by blinded pulse oximetry and capnography monitoring to detect episodes of RD. An RD episode was defined as: respiratory rate ≤ 5 breaths/min (bpm) for ≥ 3 minutes, oxygen saturation (SpO2) ≤ 85% for ≥ 3 minutes, end-tidal carbon dioxide (EtCO2) ≤ 15 or ≥ 60 mm Hg for ≥ 3 minutes, apnea episode lasting > 30 seconds, or any respiratory opioid-related adverse event. Data were used to calculate nocturnal (00:00 &boxh; 06:00) ODI4% based on desaturation episodes (4% decrease from mean oxyhemoglobin saturation in the past 120 seconds, lasting ≥ 10 seconds). Continuous monitoring began after a patient received parenteral opioids, allowing identification of potential RD and ODI4% episodes during opioid therapy. The average number of ODI4% episodes (≥ 1, ≥ 5, ≥ 10, ≥ 15 episodes/hour) were analyzed. Logistic regression and area under the receiver operating characteristic curve (AUC) were computed.Results: A final cohort of 1072 (out of 1335) patients had sufficient data, with 76% (N=817/1072) having ≥ 1 episode of ODI4%. Multivariable logistic regression showed that ODI4% was strongly associated with RD, with greater risk for higher ODI4% scores: ≥ 5 episodes/hour odds ratio 2.59 (95% CI 1.72– 3.89, p< 0.0001); ≥ 10 episodes/hour 3.39 (95% CI 1.80– 6.39, p=0.0002); ≥ 15 episodes/hour 4.71 (95% CI 1.93– 11.47, p=0.0006).There was no significant association between ODI4% and respiratory adverse events.Conclusion: Nocturnal ODI4% was highly correlated with RD among hospitalized patients receiving parenteral opioids. Patients with a high ODI4%, especially with ≥ 15 episodes/hour, are more likely to experience RD and should be evaluated for the need of closer monitoring after opioid administration.Keywords: opioids, oxygen desaturation index, respiratory depression, sleep apnea

BACKGROUND: Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. METHODS: Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. RESULTS: Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P

Introduction Despite the high incidence of respiratory depression on the general care floor and evidence that continuous monitoring improves patient outcomes, the cost–benefit of continuous pulse oximetry and capnography monitoring of general care floor patients remains unknown. This study modeled the cost and length of stay savings, investment break-even point, and likelihood of cost savings for continuous pulse oximetry and capnography monitoring of general care floor patients at risk for respiratory depression. Methods A decision tree model was created to compare intermittent pulse oximetry versus continuous pulse oximetry and capnography monitoring. The model utilized costs and outcomes from the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial, and was applied to a modeled cohort of 2447 patients receiving opioids per median-sized United States general care floor annually. Results Continuous pulse oximetry and capnography monitoring of high-risk patients is projected to reduce annual hospital cost by $535,531 and cumulative patient length of stay by 103 days. A 1.5% reduction in respiratory depression would achieve a break-even investment point and justify the investment cost. The probability of cost saving is ≥ 80% if respiratory depression is decreased by ≥ 17%. Expansion of continuous monitoring to high- and intermediate-risk patients, or to all patients, is projected to reach a break-even point when respiratory depression is reduced by 2.5% and 3.5%, respectively, with a ≥ 80% probability of cost savings when respiratory depression decreases by ≥ 27% and ≥ 31%, respectively. Conclusion Compared to intermittent pulse oximetry, continuous pulse oximetry and capnography monitoring of general care floor patients receiving opioids has a high chance of being cost-effective. Trial Registration www.clinicaltrials.gov, Registration ID: NCT02811302. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01779-7.

BACKGROUND The frequency and temporal distribution of postoperative respiratory depression (RD) events are not completely understood. This study determined the temporal distribution and frequency of RD episodes in postsurgical patients continuously monitored by bedside capnography and pulse oximetry. METHODS This was a post hoc study of a subset of postsurgical patients enrolled in The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial from 2 sites in the United States. These patients had undergone continuous bedside monitoring on general care wards. These data were adjudicated for potential RD episodes. The number of RD episodes per patient and the time of each RD episode were determined. The first RD episode experienced by a patient was classified as an "initial" episode, and the initial and all subsequent RD episodes experienced by a patient were classified as "all" episodes. A PRODIGY risk score was calculated. RESULTS Data analyzed from 250 patients contained 2539 RD episodes in 155 (62.0%, 95% confidence interval, 55.7-68.0) patients with median 2 [0-8], range of 0-545 RD episodes per patient, with a PRODIGY risk score distribution of 100 (40.0%) low, 79 (31.6%) intermediate, 70 (28.0%) high (missing data from 1 patient). Median time to the initial RD episode was 8.8 [5.1-18.0] hours postoperatively. There was a peak occurrence of initial RD events between 14:00 and 20:00 on the day of surgery, and these were associated with a large number of subsequent events in the same timeframe. The peak time of all RD episodes occurred from 02:00 to 06:00. Patients with high PRODIGY risk scores had higher incidence and greater number of RD episodes per patient (P < .001, overall comparisons between groups for both incidence [χ2] and number of episodes [Kruskal-Wallis test]). CONCLUSIONS Continuous monitoring of surgical patients demonstrates that RD episodes are common, and risk increases with higher PRODIGY scores. In this patient cohort, the rate of initial RD episodes peaked in the afternoon to early evening, while peak rate of all RD episodes occurred in early morning. Further, among patients with RD episodes, the number of episodes increased with higher PRODIGY scores.

In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p

Study objective: Opioid administration for pain in general care floor patients remains common, and can lead to adverse outcomes, including respiratory compromise. The PRODIGY trial found that among ward patients receiving parenteral opioids, 46% experienced >= 1 respiratory depression episode. The objective of this analysis was to evaluate the geographic differences of opioid administration and examine the association between opioid administration characteristics and the occurrence of respiratory depression.Design: Prospective observational trial.Setting: 16 general care medical and surgical wards in Asia, Europe, and the United States.Patients: 1335 patients receiving parenteral opioids.Interventions: Blinded, alarm-silenced continuous capnography and pulse oximetry monitoring.Measurements: Opioid-induced respiratory depression, defined as respiratory rate = 60 mmHg for >= 3 min; apnea episode lasting >30 s; or any respiratory opioid-related adverse event.Results: Across all patients, 58% received only long-acting opioids, 16% received only short-acting (= 3 h) opioids. The type and median total morphine milligram equivalent (MME) of opioid administered varied significantly by region, with 31.5 (12.5-76.7) MME, 31.0 (6.2-99.0) MME, and 7.2 (1.7-18.7) MME in the United States, Europe, and Asia, respectively (p < 0.001). Considering only postoperative opioids, 54% (N = 119/220) and 45% (N = 347/779) of patients receiving only short-acting opioids or only long-acting opioids experienced >= 1 episode of opioid-induced respiratory depression, respectively. Multivariable analysis identified post-procedure tramadol (OR 0.62, 95% CI 0.424-0.905, p = 0.0133) and post-procedure epidural opioids (OR 0.485, 95% CI 0.322-0.731, p = 0.0005) being associated with a significant reduction in opioid-induced respiratory depression.Conclusions: Despite varying opioid administration characteristics between Asia, Europe, and the United States, opioid-induced respiratory depression remains a common global problem on general care medical and surgical wards. While the use of post-procedure tramadol or post-procedure epidural opioids may reduce the incidence of respiratory depression, continuous monitoring is also necessary to ensure patient safety when receiving post-operative opioids.

BACKGROUND From 2011 to 2014, a total of 71% of the 3834 patients with hematologic malignancies successfully identified a matched unrelated donor (MUD) through the Italian Bone Marrow Donor Registry (IBMDR), corresponding to a transplant efficiency of 62%. STUDY DESIGN AND METHODS From 2006, the Rome Transplant Network (RTN) followed a hierarchical selection strategy for the alternative donor search: first MUD, second cord blood, and third haploidentical donor. Using a low-resolution HLA, a preliminary query (PQ) was performed in all cases with assignment of good or poor score if more or less than 10 MUDs were identified in Bone Marrow Donors Worldwide. Herein we assessed the utility of PQ and of high-resolution (HR) HLA from the start of the search. Moreover, we compared the donor identification and the transplant efficiency between IBMDR and RTN. RESULTS At RTN 79% of 417 patients met a good PQ with a 50% MUD identification versus 12.5% with poor PQ. Our policy led to 78 and 74% of alternative donor identification and transplant efficiency, respectively, higher than IBMDR data equal to 71% (p = 0.007) and 62% (p

The use of granulocyte colony-stimulating factor (G-CSF) primed bone marrow (G-BM) has been recently considered as an alternative to mobilized hematopoietic stem cells from peripheral blood (G-PB), especially in the haploidentical transplant setting. The purpose of this study was to compare the effect of in vivo G-CSF priming on BM and PB hematopoietic, mesenchymal (MSC), and immune cells. Forty healthy donors undergoing BM harvest for haploidentical transplant were given subcutaneous recombinant human G-CSF for 7 days. BM and PB samples were harvested on days -7 and 0. The hematopoietic stem/progenitor cells increased significantly after G-CSF priming in both BM and PB with a selective rise of BM CD34(+)CD38(-) cell subset. A striking enhancement of the mesenchymal progenitors was detected in G-BM. CD3(+), CD4(+), CD8(+), and CD19(+) cell fractions; the naive CD4(+) and CD8(+) subpopulations; and natural killer and regulatory T cells increased in G-BM, whereas only slight changes were detected in PB. Myeloid dendritic cells (DC1) were significantly up-regulated in both G-BM and G-PB, whereas DC2 increased only in G-BM. In conclusion, our results show substantial differences in the biologic effects exerted by G-CSF at BM and PB levels on hematopoietic cells and immune cell fractions. Furthermore, the impressive rise of MSC progenitors in G-BM might also be relevant to provide MSCs for several clinical use.

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.

Conventional cytology (CC) of cerebrospinal fluid (CSF) fails to demonstrate malignant cells in up to 45 % of patients with acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LL) in whom occult leptomeningeal disease is present. Flow cytometry (FCM) is considered more sensitive than CC, but clinical implications of CC negativity/CC positivity are not yet established. CSF samples from 38 adult patients with newly diagnosed ALL/LL were examined. Five (13 %) and nine (24 %) specimens were CC positive-FC positive (FCM(pos)/CC(pos)) and CC negative-FC positive (CC(neg)/FCM(pos)), respectively. The remaining 24 (63 %) samples were double negative (CC(neg)/FCM(neg)) (p = 0.001). CC(neg)/FCM(pos) patients showed a significantly shorter overall survival (OS) compared to CC(neg)/FCM(neg) ones. In multivariate analysis, the status of single FCM positivity was demonstrated to affect independently duration of OS (p = 0.005). In conclusion, FCM significantly improves detection of leptomeningeal occult localization in ALL/LL and appears to anticipate an adverse outcome. Further prospective studies on larger series are needed to confirm this preliminary observation.

Introduction: Outcome in allogeneic HSCT varies widely depending on disease type, stage, stem cell source, HLA-matched status and conditioning regimen. IFI is a possible complication of HSCT and a prior IFI increases the patient's risk for transplant related mortality due to the possibility of reactivation of the fungal infection. This study aimed to evaluate the impact of a previous IFI history on transplant outcome Methods: We retrospectively collected the clinical data of patients considered eligible for allogeneic HSCT during 2014 at the Rome Transplant Network (RTN), a JACIE accredited metropolitan transplant program established in Rome since 2006. The observation of patients was continued until 31 December 2015. The diagnosis of IFI were defined as possible, probable and proven as established by European Organization for Research and treatment of Cancer. Results: Twenty-one (37%) out of 57 eligible patients had an IFI episode before transplant: 6 of the episodes were proven, 4 probable and 11 possible. Overall, 10 (47%) pneumonia, 4 (19%) gastroenteritis, 3 sinusitis, 2 candida sepsis, 1 meningitis and 1 cutaneous abscess were registered. Five out of 21 patients (23%) died before HSCT versus 2 of 36 patients (5%) without previous documented IFI, [OR 5.31 95% CI 0.93- 30.40 , p value 0.06 Fisher Test], . A larger percentage of patients with past IFI waited HSCT over 6 months from the date of eligibility in comparison with those without previous IFI [43% vs 30% ; OR 1.87 95% CI 0.54-6.40 , p value 0.5 Yates test]; Sixteen (57%) out of 28 dead patients in the pre-transplant period have had a previous IFI episode vs 5(17%) out of patients alive [OR 6.4, 95% CI 1.89-21.68, p value: 0.004 Yates Test]. In the post-transplant period, only 6% of patients with a past IFI, experienced an engraftment in a time of < 15 days, vs 30% of patients without past IFI [OR 4.86 CI 95% 0,5-43,2, p value 0,2 Yates test]. In the post-transplant period, a IFI was diagnosed in 13 (26%) patients; ten (76%) out of 13 patients had a past IFI versus 9 (24%) of the patients without IFI.. [OR 7.87, CI 95% 1,8-34,2, p value 0,005 Yates test].Among the dead HSCT patients, those who had a previous IFI had a lower median survival [160 days (range 22- 480)] compared to patients without a previous IFI who died [196.5 days period (range 20-820)]. Conclusions: A previous IFI episode in the pre transplant period slow the accessibility to the transplant, adversely affects the engraftment, and is significantly associated with increased post-transplant mortality Disclosures No relevant conflicts of interest to declare.

Introduction Central venous catheters (CVC) related thrombosis (CRT) represents a well known complication in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy but the efficacy of antithrombotic prophylaxis still remains controversial. Patients and Methods We analyzed 71 consecutive AML patients whose CVC was inserted before each chemotherapy cycle for an overall number of 106 CVC placements. In 47/106 insertions, a prophylaxis with 100 IU/kg/day low molecular weight heparin (LMWH) was administered for 7 days after CVC insertion and additional 7 after CVC removal. This unconventional dose of LMWH, although higher than usual, appeared adequate for a short-course approach. LMWH was delivered regardless of the platelet (PLT) count once provided that it should have been maintained above 20x109/L by transfusions. Results Of 106 insertions, we observed 19 (18%) episodes of CRT, 58 (54%) of sepsis and 50 (47%) infections of CVC-exit site with no difference between LMWH and no-LMWH group. Occurrence of CRT was significantly associated with CVC-exit site infections (14/19, p = 0.01) and sepsis (16/19, p = 0.005) with no difference between LMWH and no-LMWH group. In multivariate analysis, both CVC-exit site infections and sepsis were confirmed to be independent risk factors for CRT development. Conclusion Our retrospective study, although based on a small sample size, suggests that the occurrence of CVC-exit site infections and neutropenic sepsis following chemotherapy significantly increases the risk of CRT in AML, independently from the use of LMWH prophylaxis.

Background. During the last years, hematopoietic stem cell transplant from haploidentical donor is increasing by using the unmanipulated graft. We report the results of allogeneic bone marrow transplantation (BMT) from haploidentical donor primed with G-CSF in patients (pts) with high-risk acute myeloid leukemia (AML), who received an uniform TBF (Thiotepa, Busulfan, Fludarabine) conditioning regimen including antitymocyte globulin and an identical GVHD prophylaxis combining MTX+CSA, MMF and an anti-CD25 monoclonal antibody (Basiliximab). Patients and Methods. Since August 2005 to December 2014, 165 pts with high-risk hematological malignancy underwent unmanipulated BMT from fully haploidentical donor primed with 4µg/kg/day of G-CSF over 7 days. Of these 165 pts, 71 (median age 49 yrs, (range5-66) were affected by high-risk AML and were in early (CR1 and CR2: n=58) or advanced (>CR2 or active disease: n=13) phase at time of transplant. All pts received the same myeloablative (MAC: n=47) or reduced intensity (RIC: n=24) TBF conditioning regimen including antithymocyte globuline for 4 days (days-4 through -1) and an identical graft-versus-host disease (GVHD) prophylaxis consisting of the classical association of MTX+CSA combined with MMF from day +7 to day +100 and the administration of 20 mg of Basiliximab at days 0 and +4. The donor were represented by: son (n=25); brother (n=18), mother (n=11), daughter (n=8), sister (n=6) and father (n=3). Anti-infective management, supportive care and transfusion policy were identical for all pts. The experience was conducted at 2 Institutions: Stem Cell Transplant Unit at University Tor Vergata of Rome (n=45) and at Civil Hospital of Pescara (n=26), Italy. Results. All pts engraftedwith full donor chimerism: median time 20 days (range, 11-35) and CI 94±3%. With a median follow-up (FU) of 3.9 yrs (range, 0.7-7.4), the 7-yrs probability of overall survival (OS) and disease free survival (DFS) for all pts was 45±6% and 43±6%, respectively. OS calculated by disease status at transplant was 53±7% at 7 yrs for 58 pts transplanted in early phase and 0.0% at 4 yrs for 13 transplanted in advanced phase (p=0.0027), DFS was 49±7% and 15±10% at 7 and 2 yrs (p=0.007), respectively. TBF-MAC Regimen: 47 pts (median age 43 yrs, range 5-63), in early (n=38) or advanced (n=9) phase at transplant received a TBF-MAC regimen. For all these pts the CI of engraftment was 94±4% at a median of 20 days (range, 12-35). The 100 day CI of acute GVHD (AGVHD) grade II-IV and III-IV was 32±7% and 6±4%, respectively. The CI of extensive chronic-GVHD (CGVHD) was 19±7%. In the patients transplanted in early phase the CI of transplant related mortality (TRM) at 6 months and 7 yrs was 21±7 and 27±7%, respectively. The CI of relapse at 1 and 7 yrs was 16±6% and 24±7%, respectively. With a median FU of 3.9 yrs (range, 1.3-7.4), the 7-yr probability of OS and DFS was respectively 60±8% and 52±8% with a plateau of the curve from 2 yrs after transplant. None of the 15 variables considered in multivariate analysis (Cox and Fine and Gray models) influenced significantly the outcomes. TBF-RIC Regimen: 24 pts (median age 61.5 yrs, range 41-66) were conditioned with TBF-RIC. All pts engrafted with full donor chimerism (CI 96±6%). The 100 day CI of AGVHD grade II-IV and III-IV was 33±10% and 13±7%, respectively. The CI of extensive CGVHD was 8±8%.Four pts were in advanced and 20 in early phase at transplant. For these last pts, the CI of TRM at 6 months and 6 yrs was 15±8% and 25±10%, respectively. The CI of relapse at 1 and 6 yrs was 15±8% and 27±11%, respectively. With a median FU of 4.1 yrs (range, 0.8-6), the 6-yr probability of OS and DFS was respectively 42±12% and 41±12% with a plateau of the curve from 2 yrs after transplant. In multivariate analysis, no significant factor was identified. Conclusions. Although the number of pts does not allow an extensive analysis of the results, the homogeneity of our series in terms of diagnosis, patient selection, conditioning regimen and GVHD prophylaxis supports the conclusion that haploidentical, G-CSF primed, unmanipulated BMT is a valid alternative for high-risk AML pts lacking an HLA identical sibling. The regimen of GVHD prophylaxis is highly effective and can be proposed in alternative to the use of post-transplant cyclophosphamide, proposed by the Baltimore group. Finally, TBF-RIC regimen can be confidently offered to unfit or older AML pts candidate to an haploidentical transplant. Disclosures No relevant conflicts of interest to declare.

Patients and Methods. At the Rome Transplant Network, a JACIE accredited metropolitan transplant program, a matched-pair analysis has been conducted on 116 of 255 patients transplanted between January 2008 and December 2012. The patients transplanted from Id Sib (n=58) or Haplo related donors (n=58) were completely matched for the following features: patient age, gender, diagnosis (7 subgroups), disease phase (early: CR1+CR2; advanced: >CR2+active disease), myeloablative or reduced intensity conditioning regimen consisting of Thiotepa, i.v. Busulphan and Fludarabine (TBF) association, donor age and donor/recipient sex, AB0 and CMV combinations. As GVHD prophylaxis, all patients received the standard CSA and MTX combination with the addition of ATG, MMF and Basiliximab in Haplo bone marrow recipients. The transfusion policy, supportive care and antinfectious prophylaxis were identical for all patients. Results. By comparingId Sib to Haplo recipients, the cumulative incidence (CI) of grade II-IV and III-IV acute-GVHD was 18±5% vs 42±7% (p=0.002) and 7±3% vs 14±5% (p=ns), respectively. The CI of extensive chronic GVHD was 23±6% for both patient series. The 5-year CI of TRM was 30±6% vs 36±6% (p=ns), respectively. The main causes of TRM were infections and the 6-month CI of Infection Related Mortality (IRM) was 26±6% in Haplo transplant and 10±4% in Id Sib (p=0.04). Although not statistically significant, the 5-year CI of relapse was higher in Id Sib (40±7%) than in Haplo recipients (28±6%). With a median follow-up of 3.5 years (range, 1 - 6), the 1- and 5-year disease free survival (DFS) was respectively 50±7% and 37±6% for Id Sibs and 45±7% and 36±6% for Haplo (Figure 1). Since 2 years after transplant, DFS curves of Id Sib and Haplo patients remained at plateau and were overlapping. Conclusions. This analysis considered a high number of factors for matching patients, who were grafted according to an identical transplant program. We can conclude that as consequence of a more intensive GVHD prophylaxis and therapy ensuing from higher incidence of >II grade acute GVHD, Haplo recipients are mainly exposed to a risk of early infection mortality. On the other hand, Id Sib patients seem to express less graft-versus-tumor activity with increasing risk of relapse after transplant. The identical long-term DFS justifies to consider the unmanipulated bone marrow transplant from haploidentical donor a valid alternative for patients lacking an HLA identical sib. Finally, it can appear at present provocative, but certainly realistic in perspective, the hypothesis that the donor choice in a familiar setting will mainly take into account other favourable donor/recipient combined characteristics rather than HLA compatibility. Figure 1 - Disease Free Survival Figure 1. - Disease Free Survival Disclosures No relevant conflicts of interest to declare.

Background. Similar probabilities of survival have been reported for patients transplanted from Matched Unrelated Donor (MUD), Umbilical Cord Blood (UCB) or Haploidentical (Haplo) donors as alternative hematopoietic stem cell sources. However, few studies have compared these results with those obtained in patients transplanted from HLA Id-siblings (Id-sib). Moreover, all reported studies are retrospective and the criteria of donor selection were not predefined. We report the intention to treat (ITT) analysis results on 238 patients with high-risk acute myeloid leukemia (AML) prospectively transplanted according to the policy of the Rome Transplant Network (RTN), a metropolitan transplant program established in Rome in 2006. Patients and Methods. For AML patients eligible to an allogeneic transplant, the RTN policy consists of an algorithm of donor choice based on a hierarchy according to the following criteria: 1) HLA identical sibling; 2) MUD ≥8/10 HLA 3) UCB as single unit selected on the base of cell dose and number of HLA disparities (0-1/6 HLA: TNC ≥2.5x107/kg and CD34 ≥1x105/kg; 2/6 HLA: TNC ≥3.5x107/kg and CD34 ≥2x105/kg); 4) G-CSF primed, unmanipulated bone marrow Haplo donor. Myeloablative (MAC) or reduced intensity (RIC) TBF (Tiothepa, Busulfan, Fludarabine) conditioning regimen was identical for all patients, GVHD prophylaxis was uniform for each categories. of transplant Results. From January 2006 to December 2014, 238(89%) out of 303 adult patients candidates to an allogeneic transplant for high-risk AML were considered eligible. Overall, a donor was available for 205 (86%) of 238 eligible patients. At time of the analysis, 17 of these 205 patients (8%) had lost the transplant eligibility and 4 (2%) were still scheduled for transplant, therefore 184/205 (90%) patients with an available donor were finally transplanted from Id-sib (n=76), MUD (n=38), UCB (n=17) or Haplo (n=53) donors. The 8-yrs overall survival (OS) of the 238 eligible patients from time of HLA typing and of the 184 transplanted patients from time of the graft was 40±4%and 43±4%, respectively. By excluding the low number of UCB recipients (n=17), the OS was particularly dismal for the 34 patients transplanted in advanced disease phase (7±4% at 4 yrs), whereas for the 132 patients transplanted in early (CR1+ CR2) phase the 8-yr OS was 56±5%: 58±7% for 61 HLA Id-sib, 50±8% for 40 Haplo and 63±10% for 27 MUD recipients (P=NS). The OS of patients transplanted in early phase was 63±5% for 97 patients receiving MAC and 33±9% for RIC recipients. For these 97 patients, the survival by type of donor was 62±10% either for 47 Id-sib or 28 Haplo and 70±10% for 22 MUD recipients (P=NS). The results were analyzed by various donor/recipient (D/R) combinations such as age, sex and CMV status. The median donor age was 39 years (range, 18-70) and the median patient age was 43 years (range, 16-59): the 8-yr OS of patients (n=30) with younger D/R combination (D Conclusions. RTN policy allowed donor identification in 86% of all eligible AML patients and allowed an allogeneic transplant to be carried out in 90% of them with no substantial differences in terms of long-term survival between initially eligible (ITT analysis) and definitively transplanted patients. Only the definition of a specific transplant policy and the ITT analysis allow to evaluate the real impact of a transplant program. As the probability of survival is not substantially different comparing different donor stem cell sources, the final conclusion which can be drawn from our study is that for patients with AML undergoing an allogeneic transplant, the HLA matching is unlikely to remain the first criterion for donor identification. Other factors such as D/R age, sex and CMV status should drive the search for the best donor. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.