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Background: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. Observations: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. Conclusions and relevance: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery. [ABSTRACT FROM AUTHOR]

Background: Polymerase chain reaction (PCR) assays are perceived to facilitate the diagnosis of fungal infections. However, due to lack of standardization, the value of bronchoalveolar lavage (BAL) fluid PCR in diagnosis of invasive pulmonary aspergillosis (IPA) remains unclear. Methods: We conducted a systematic meta-analysis to evaluate the accuracy of BAL fluid PCR in IPA diagnosis among high-risk patients. All studies involving patients at risk for IPA were included. The sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR were summarized for diagnosis of proven/probable IPA, or proven IPA only. Potential heterogeneity was assessed by subgroup analyses and meta-regression. Results: Forty-one studies involving 5668 patients were analyzed. The summary sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR for proven/probable IPA were 0.75 (95% CI = 0.67–0.81), 0.94 (95% CI = 0.90–0.96), 11.8 (95% CI = 7.7–18.1) and 0.27 (95% CI = 0.20–0.36), respectively. Whereas for proven IPA only, sensitivity and specificity were 0.91 (95% CI = 0.68–0.98) and 0.80 (95% CI = 0.74–0.85) in fourteen studies involving 2061 patients. Significant heterogeneity was present due to the underlying disease, antifungal treatment and differences in DNA extraction techniques and choice of PCR assay. Compared to patients with hematological malignancies (HM) and hematopoietic stem cell/solid organ transplantation (HSCT/SOT), sensitivity was higher in the population with disease such as chronic obstructive pulmonary disease, solid tumor, autoimmune disease with prolonged use of corticosteroids, etc. (0.88 vs. 0.68, P < 0.001), which was related to the concurrent use of antifungal prophylaxis among patients with HM and HSCT/SOT. Conclusion: BAL fluid PCR is a useful diagnostic tool for IPA in immunocompromised patients and is also effective for diagnosing IPA in patients without HM and HSCT/SOT. Furthermore, standard protocols for DNA extraction and PCR assays should be focused on to improve the diagnostic accuracy. Trial registration PROSPERO, registration number CRD42021239028. [ABSTRACT FROM AUTHOR]

Background: Therapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients.Methods: This retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January-June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July-December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July-December 2021/total TDM results July-December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal (< 12 h), quasi-optimal (12-24 h), acceptable (24-48 h), suboptimal (> 48 h)].Results: The OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin-tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre-post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal.Conclusions: Multidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates. [ABSTRACT FROM AUTHOR]

Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment. [ABSTRACT FROM AUTHOR]

Background: Sequential monitoring of Wilms' tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children.Methods: Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan-Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM.Results: Of the 151 consecutive patients included, the median age was 10 years (range, 1-17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25-6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies.Conclusions: Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival. [ABSTRACT FROM AUTHOR]

Background: Mock-up based approach allows the preview of the aesthetic rehabilitation, however, it is crucial that the mock-up does not differ from the expected aesthetic outcomes. With CAD-CAM technologies, it is possible to directly create mock-ups from virtual planned smile project, with greater accuracy and efficiency compared to the conventional moulded mock-ups. In this study, we investigated the trueness of mock-ups obtained with milling and 3D printing technology and a full digital work-flow system. Methods: Ten adults subjects were included and digital smile design/digital wax-up were performed to enhance the aesthetic of maxillary anterior region. Ten milled mock-ups and 10 prototyped mock-ups were obtained from the original.stl file and a digital analysis of trueness was carried out by superimposing the scanned-milled mock-ups and the scanned-prototyped mock-ups to the digital wax-up, according to the surface-to-surface matching technique. Specific linear measurements were performed to investigate and compare the dimensional characteristics of the physical manufactures, the 3D project and the scanned mock-ups. All data were statistically analyzed. A clinical test was also performed to assess the fitting of the final manufacture. Results: The prototyped mock-ups showed a significant increment of the transversal measurements (p < 0.001) while the milled mock-ups showed a significant increment of all vertical and transversal measurements (p < 0.001). The prototyped mock-ups showed good fitting after clinical tests while none of the milled mock-ups showed good adaptation (no fitting or significant clinical compensation required). Deviation analysis from the original 3D project reported a greater matching percentage for the scanned-milled mock-ups (80,31% ± 2.50) compared to the scanned-prototyped mock-ups (69,17% ± 2.64) (p < 0.001). This was in contrast with the findings from linear measurements as well as from the clinical test and may have been affected by a reductive algorithmic computation after digitization of physical mock-ups. Conclusion: Both prototype and milled mock-ups showed a slight dimensional increment comparing to the original 3D project, with milled-mock-ups showing less fitting after clinical tests. Caution must be taken when assessing the trueness of scanned manufacture since an intrinsic error in the system can underestimate the dimensions of the real object. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been considered as a valuable approach in treatment of numerous malignant and none malignant hematologic disorders. However, relapse and poor graft function (PGF) after allo-SCT remain to be controversial issues which may affect the transplantation outcome. Relevant articles were searched in MEDLINE database (2000-2016) using keywords and phrases: donor lymphocyte infusions, allogeneic stem cells transplantation, relapsed hematologic malignancies, booster schedules, cell dose, laboratory monitoring protocols and technical aspects of apheresis. Relapse of disease and PGF could be reduced via noting some main points such as choosing the suitable time and patient for donor lymphocyte infusion (DLI) and also determination of patients who ought to candidate for second allogeneic HSCT or for the use of stem cell boost. DLI and stem cell booster are promising treatment strategies noted in this review. Finally, this paper discusses indications and technical aspects of DLI and stem cell booster in hematological malignancies and emphasizes their therapeutic or pre-emptive potentials. [ABSTRACT FROM AUTHOR]

Background: Allogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors. Methods: We performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014. Results: Median age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on antithymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II-IV acute-graft-versus-host-disease (GVHD) was 31%, grade III-IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS. Conclusions: Unmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status. [ABSTRACT FROM AUTHOR]

Background: In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT) from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo) versus matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10) for patients with acute leukemia in remission. Methods: Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. Results: The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS) and overall survival (OS) were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease. Conclusions: Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. Key point 1: Better outcomes using fully (10/10) matched unrelated donor for allo-SCT in acute leukemia in remission. Key point 2: Similar outcomes after allo-SCT from unmanipulated haploidentical graft or mismatched (9/10) unrelated donor in acute leukemia in remission. [ABSTRACT FROM AUTHOR]

Background: Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple consolidation chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction chemotherapy and DLI. Methods: Forty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction chemotherapy and DLI were eligible. The use of consolidation chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive consolidation chemotherapy and DLIs after induction chemotherapy and DLI. Results: One-year cumulative incidence of relapse (CIR; 22% 95% confidence interval (10, 35%) vs. 56% (39, 73%); P < 0.0001), leukemia-free survival (LFS; 71% (57, 84%) vs. 35% (19, 51%); P < 0.0001), and survival (78% (66, 90%) vs. 44% (27, 61%); P < 0.0001) was significantly better in subjects than controls. In multivariate analyses, no chronic GvHD after therapy (hazard ratio (HR) = 3.56 (1.09, 11.58); P = 0.035) and a positive MRD test after therapy (HR = 21.04 (4.44, 94.87); P < 0.0001) were associated with an increased CIR. Conclusion: These data suggest MRD- and GvHD-guided multiple consolidation chemotherapy and DLIs reduce CIR and increase LFS and survival compared with controls in persons relapsing after allotransplant for acute leukemia. [ABSTRACT FROM AUTHOR]

In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we focused on factors associated with transplant outcomes following unmanipulated haplo-SCT with anti-thymocyte globulin (ATG) or after T-cell-replete haplo-SCT with post-transplantation cyclophosphamide (PT/Cy). We summarized the effects of the primary factors, including donor-specific antibodies against human leukocyte antigens (HLA); donor age and gender; killer immunoglobulin-like receptor-ligand mismatches; and non-inherited maternal antigen mismatches. We also offered some expert recommendations and proposed an algorithm for selecting donors for unmanipulated haplo-SCT with ATG and for T-cell-replete haplo-SCT with PT/Cy. [ABSTRACT FROM AUTHOR]

Background: Since the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients. Methods: We analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients' posttransplantation following detection of BCR-ABL transcripts. Results: All of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p < 0.05) and chronic GVHD (48.9 vs. 25.7 %, p < 0.05) compared with HLA-matched HSCT, but there was no difference in the incidence of either grades III-IV acute GVHD or extensive chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly higher in the patients treated with haploidentical HSCT than in those treated with HLA-matched HSCT (38.3 vs. 14.3 %, p < 0.05). Haploidentical HSCT was associated with a significantly lower relapse rate compared with HLA-matched HSCT (44.8 vs. 19.1 %, p < 0.05). There were no differences in non-relapse mortality (NRM), leukemia-free survival (LFS), or overall survival (OS) between the patients who received HLA-matched HSCT and those who underwent haploidentical HSCT. Conclusions: Our data indicate that the incidence of NRM after HSCT is similar between the patients who receive HLA-matched donor cells and those who receive haploidentical donor cells and that haploidentical HSCT reduces the relapse rate. Haploidentical HSCT represents an encouraging treatment option for Ph+ ALL patients who lack a suitable HLA-matched donor. [ABSTRACT FROM AUTHOR]

Background In the past ten years there have been three separate outbreaks of fungal contaminated steroid injections from compounding pharmacies. The 2012 outbreak of central nervous system fungal infections associated with contaminated methylprednisolone produced by a United States compounding pharmacy has led to 750 infections (151 with meningitis and paraspinal infections and 325 cases with paraspinal infections without meningitis) and 64 deaths as of October 23, 2013. Exserohilum rostratum has been the predominant pathogen identified by culture, polymerase chain reaction or antibody tests. According to previous reports, cerebral involvement with phaeohyphomycosis has a high risk of morbidity and mortality. Case presentation We report a 41 year-old Caucasian woman who received a lumbar methylprednisolone injection from a contaminated lot in August 2012. She was diagnosed with fungal meningitis by cerebrospinal fluid pleocytosis and positive (1, 3) beta-D-glucan after cultures and polymerase chain reaction were negative. Two weeks after onset of therapy, she developed a 4.1 mm superior cerebellar artery mycotic aneurysm associated with new stroke symptoms, which resolved with thirty-two weeks of antifungal treatment. Conclusions This is the rare case report of successful medical management of a cerebral mycotic aneurysm with stroke symptoms related to a presumed phaeohyphomycosis in an immunocompetent individual. Further studies are needed to determine the utility of cerebrospinal fluid (1, 3) beta-D-glucan in diagnosing and monitoring patients with meningitis thought to be related to fungal infection. [ABSTRACT FROM AUTHOR]

Background: The population of survivors following allogeneic HSCT continues to increase, and yet their experiences of recovery and long-term survivorship have not been fully characterized. This paper presents a study protocol examining over time the functional status, psychosocial adjustment, health-related quality of life, and symptom experience of survivors who have undergone allogeneic transplantation. The aims of the study are to: 1) explore the patterns of change in these health outcomes during the survivorship phase; 2) characterize subgroups of survivors experiencing adverse outcomes; and 3) examine relationships among outcomes and demographic and clinical factors (such as age, graft-versus-host disease (GVHD), and disease relapse).Methods: In this longitudinal observational study, adults who survive a minimum of 3 years from date of allogeneic transplantation complete a series of questionnaires annually. Demographic and clinical data are collected along with a series of patient-reported outcome measures, specifically: 1) Medical Outcomes Study SF- 36; 2) Functional Assessment of Chronic Illness Therapy (FACIT) - General, 3) FACIT-Fatigue; 4) FACIT- Spiritual; 5) Psychosocial Adjustment to Illness Scale; 6) Rotterdam Symptom Checklist-Revised; and 7) Pittsburgh Sleep Quality Index.Conclusions: This study will provide multidimensional patient-reported outcomes data to expand the understanding of the survivorship experience across the trajectory of allogeneic transplantation recovery. There are a number of inherent challenges in recruiting and retaining a diverse and representative sample of long-term transplant survivors. Study results will contribute to an understanding of outcomes experienced by transplant survivors, including those with chronic GVHD, malignant disease relapse, and other late effects following allogeneic transplantation.Trial Registration: ClinicalTrials.gov: NCT00128960. [ABSTRACT FROM AUTHOR]

Background: As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Methods: Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse. Results: The cumulative incidence of relapse at 3 years was 44% (35–53%) for ALL and 32% (27–36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016). Conclusions: Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%). [ABSTRACT FROM AUTHOR]

Background: Limited data is available to guide the choice of the conditioning regimen for patients with acute myeloid leukemia (AML) undergoing transplant with persistent disease. Methods: We retrospectively compared outcome of fludarabine-treosulfan (FT), thiotepa-busulfan-fludarabine (TBF), and sequential fludarabine, intermediate dose Ara-C, amsacrine, total body irradiation/busulfan, cyclophosphamide (FLAMSA) conditioning in patients with refractory or relapsed AML. Results: Complete remission rates at day 100 were 92%, 80%, and 88% for FT, TBF, and FLAMSA, respectively (p = 0.13). Non-relapse mortality, incidence of relapse, acute (a) and chronic (c) graft-versus-host disease (GVHD) rates did not differ between the three groups. Overall survival at 2 years was 37% for FT, 24% for TBF, and 34% for FLAMSA (p = 0.10). Independent prognostic factors for survival were Karnofsky performance score and patient CMV serology (p = 0.01; p = 0.02), while survival was not affected by age at transplant. The use of anti-thymocyte globulin (ATG) was associated with reduced risk of grade III–IV aGVHD (p = 0.02) and cGVHD (p = 0.006), with no influence on relapse. Conclusions: In conclusion, FT, TBF, and FLAMSA regimens provided similar outcome in patients undergoing transplant with active AML. Survival was determined by patient characteristics as Karnofsky performance score and CMV serology, however was not affected by age at transplant. ATG appears able to reduce the incidence of acute and chronic GVHD without influencing relapse risk. [ABSTRACT FROM AUTHOR]

Background: Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established. Methods: This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics. Results: SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002). Conclusions: Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM. [ABSTRACT FROM AUTHOR]

Background: Multiresistant bacteria (MRB) is an increasing problem. Early identification of patients with MRB is mandatory to avoid transmission and to target the antibiotic treatment. The emergency department (ED) is a key player in the early identification of patients who are colonized with MRB. There is currently sparse knowledge of both prevalence and risk factors for colonization with MRSA, ESBL, VRE, CPE and CD in acutely admitted patients in Western European countries including Denmark. To develop evidence-based screening tools for identifying carriers of resistant bacteria among acutely admitted patients, systematic collection of information on risk factors and exposures is required. Since a geographical variation is suspected, it is desirable to include emergency departments across the country. The aim of this project is to provide a comprehensive overview of prevalence and risk factors for MRSA, ESBL, VRE, CPE and CD colonization in patients admitted to Danish ED's. The objectives are to describe the prevalence and demography of resistance, co-infections, to identify risk factors for carrier state and to develop and validate a screening tool for identification of carriers.Methods: Multicenter descriptive and analytic cross-sectional survey from January-May 2018 of around 10.000 acutely admitted patients > 18 years in 8 EDs for carrier state and risk factors for antibiotic resistant bacteria. Information about the background and possible risk factors for carrier status together with swabs from the nose, throat and rectum is collected and analyzed for MRSA, ESBL, VRE, CPE and CD. The prevalence of the resistant bacteria are calculated at hospital level, regional level and national level and described with relation to residency, sex, age and risk factors. A screening model for identification of carrier stage of resistant bacteria is developed and validated.Discussion: The study will provide the prevalence of colonized patients with resistant bacteria on arrival to the ED and variation in demographic patterns, and will develop a clinical tool to identify certain risk groups. This will enable the clinician to target antibiotic treatments and to reduce the in-hospital spreading of resistant bacteria. This knowledge is important for implementing and evaluating antimicrobial stewardships, screening and infection control strategies.Trial Registration: Clinicaltrials.gov : NCT03352167 (registration date: 20. November 2017). [ABSTRACT FROM AUTHOR]