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Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Methods Study design and data collection This was a retrospective multicenter analysis using the dataset of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Trans- plantation (EBMT) registry. The EBMT is a voluntary working group of more than 600 transplant centers that are required to report all consecutive stem cell trans- plantations and follow-ups once a year. Audits are rou- tinely performed to determine the accuracy of the data. The eligibility criteria for this analysis included adult patients ≥ 18  years of age with AML who underwent a first allo-HCT using CBT or MMUD with PTCy between 2010 and 2019. The MMUD was defined as an unrelated donor with single HLA-allele mismatch at one of the fol- lowing HLA loci A, B, C, DRB1, or DQB1. CBT using single or double cord blood units without PTCy were included in the analysis. The exclusion criteria were allo- HCT from any other donor source; a previous history of allo-HCT; use of ex  vivo graft manipulation; or lack of information on HLA matching or GVHD prophylaxis. We also excluded six patients with a pre-transplant dis- ease status of third complete remission found only in the MMUD group. Data collected included recipient and donor characteristics [age, gender, and cytomegalovi- rus (CMV) serostatus], baseline Karnofsky performance status (KPS), disease features and status at transplant, year of transplant, type of conditioning regimen, stem cell source, GVHD prophylaxis regimen, and the use of in vivo T cell depletion (TCD). The conditioning regimen
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Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Abstract Background: Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. Methods: We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3 –157) months.
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Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood

Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood

Correspondence: celsoarrais@gmail.com We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignan- cies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor trans- plant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P<0.0001) and chronic graft-versus-host disease (26%
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The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.

The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.

©1999, Ferrata Storti Foundation Key words: bone marrow transplantation, unrelated donor, GVHD A llogeneic bone marrow transplantation (allo- BMT) has become the treatment of choice for a variety of hematologic malignancies, bone marrow failures and congenital disorders of the lym- phohematopoietic system. However, the majority of patients who could benefit from an allo-BMT lack a suitable family donor. Therefore, registries of unrelat- ed volunteer marrow donors have been developed in many countries, offering the possibility of unrelated donor bone marrow transplantation (UDBMT). 1-3
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The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party

The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party

The feasibility of haplo-identical SCT performed with T replete stem cell grafts and in vivo T cell depletion based either on ATG [32] or post-transplant cyclophos- phamide [33] has been demonstrated in the past 10 years. Comparisons of haplo-identical SCT using the Chinese approach combining T replete G-CSF mobilized bone marrow stem cell graft, a myeloablative conditioning regimen with ATG, to matched related and unrelated allo-SCT for acute leukemias have shown equivalent OS with reduced risk of relapse in high-risk leukemias in the haplo-identical groups [34, 35]. Using this approach, the Beijing’s group recently reported similar outcomes in fit patients transplanted above 50 years of age in com- parison to younger patients [36]. In the setting of post- transplant cyclophosphamide, Blaise et al. reported in patients older than 60 years inferior outcomes of RIC allo-SCT performed with HLA 10/10 and 9/10 URD compared to those transplanted with MRD or haplo- identical donors because of higher NRM related to higher incidence of acute and chronic GVHD [37]. Com- parisons of haplo-identical SCT at the era of post- transplant cyclophosphamide to URD have shown simi- lar LFS and OS but reduced NRM and chronic GVHD with T replete haplo-SCT [38–41]. From 2012 onward, there has been increasing numbers of transplants per- formed from related haplo-identical donor, which is likely mainly due to increased use of haplo-identical do- nors with the post-transplant cyclophosphamide strat- egy. In AML patients undergoing allo-SCT without an HLA-matched (related or unrelated) donor, the decision to use one alternative graft source over another is com- plex. Published data support any one of the three alter- native donor allo-SCT options (i.e., mM-URD, CBT, related haplo-identical) currently available for patients without a matched donor. Our current study support this notion as results of mM-URD in AML patients with age above 50 years transplanted in CR1 were inferior to matched URD and therefore other alternative like Haplo-SCT and CBT may be considered.
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Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT

Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT

Com- parison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft- versus-host-disease prophylaxis for matched unrelated donor transplant in acute [r]

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Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Keywords: Acute myeloid leukemia (AML), Allogeneic transplantation, Matched (10/10) and mismatched (9/10) unrelated donor transplantation, Autologous transplantation, Post-remission therapy Abbreviations: ALWP, Acute leukemia working party; AML, Acute myeloid leukemia; ATT, Average treatment effect among the treated; auto-HSCT, Autologous stem cell transplantation; BM, Bone marrow; CBF, Core-binding factor; CEBPA, CCAAT/enhancer-binding protein alpha; CR1, First complete remission; EBMT, European society for blood and marrow transplantation; ELN, European leukemia net; FLT3-ITD, fms-like tyrosine kinase-internal tandem duplication; GIMEMA, Gruppo Italiano Malattie EMatologiche dell ’Adulto; GVHD, Graft-vs-host disease; GVL, Graft-vs-leukemia; LFS, Leukemia-free survival; MAC, Myeloablative; MMUD, Mismatched unrelated donor; MRD, Minimal residual disease; MSD, Matched sibling donor allo-HSCT; MUD, Matched unrelated donor; NCCN, National Comprehensive Cancer Network; NPM1, Nucleophosmin; NRM, Non-relapse mortality; OS, Overall survival; PBSCs, Peripheral blood stem cells; PS, Propensity score; RI, Relapse incidence; RIC, Reduced-intensity; TBI, Total-body irradiation; WBC, White blood cells; wtFLT3, Wild-type FLT3; 10/10 UD-HSCT, Unrelated donor transplantation matched at 10/10 HLA loci; 9/10 UD-HSCT, Unrelated donor transplantation mismatched at a single HLA-locus
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ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT.

ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT.

While MMURD transplantation presents an attractive and readily avail- able option for some patients, widespread use has been limited to some degree by an increased risk for graft failure, 2 –4 higher rates of GVHD, 5,6 and an increased risk of nonrelapse mortality (NRM), 7 all of which may lead to compromised survival. Thus, improving on transplant related out- comes in MMURD is a major priority in the field of alternative donor transplantation. ABO incompatibility involves antibody production against donor red blood cells (major ABO incompatibility) or against the recipi- ent ’s red blood cells (minor ABO incompatibility) and is seen in 25–50% of allogeneic stem cell transplantations. 8,9 Yet, it remains unclear whether
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Unrelated donor haemopoietic stem-cell transplantation: ATG or not?

Unrelated donor haemopoietic stem-cell transplantation: ATG or not?

with ciclosporine and methotrexate with or without additional ATLG (60 mg/kg total dose) in patients given grafts (mainly peripheral blood stem-cells) from unrelated donors. Median follow-up was 8·6 years. The main observations were that, at 8 years, the probability of being alive and free of immunosuppressive therapy was 11% (95% CI 5–18) in the non-ATLG group versus 47% (37–57) in the ATLG group (p=0·0002), while severe GVHD-free and relapse-free survival (which serves as a measure of cure without ongoing morbidity) was 13% (95% CI 7–21) in the non-ATLG group versus 34% (25–43) in the ATLG group (p=0·0003; figure 1). Relapse mortality was not increased by ATLG (adjusted HR 1·03, 95% CI 0·61–1·76; p=0·90), which is reassuring regarding the long-term safety of ATLG. Finally, 8-year overall survival was 37% (27–47) in non-ATLG patients versus 49% (39–59) in ATLG patients (p=0·3).
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Stem cell transplantation in ALL : a donor versus no donor comparison in the EORTC ALL-4 study

Stem cell transplantation in ALL : a donor versus no donor comparison in the EORTC ALL-4 study

Improvement in molecularly matching unrelated donors to patients, and the development of more safely using UCB transplants in adults, may result in more patients with MyMal in need of an alloSCT undergoing this procedure, a devel- opment strongly needed as in 2006, approximately 80% of patients dependent on identifying an unrelated donor source were unable to proceed to an alloSCT in the U.S.

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Adoptive immunotherapy with donor lymphocyte infusions after allogeneic HPC transplantation.

Adoptive immunotherapy with donor lymphocyte infusions after allogeneic HPC transplantation.

several patients developed moderate to severe GVHD. To di- minish the risk of GVHD, researchers at one institution 44,65,67,85,86 transfused specific anti-EBV donor T cells induced ex vivo with EBV-transformed B-lymphoblastoid cell lines. Donor-de- rived EBV-specific CTLs were transfused 45 days after allo- geneic BM transplant in 50 patients at high risk of develop- ing EBV lymphoma after T-cell-depleted transplantation from a matched unrelated donor or a mismatched related donor. None of the patients developed EBV-induced lym- phoproliferative disease, whereas there was a cumulative risk of 11 percent in patients who did not receive this treat- ment. Moreover, two patients who were treated for clinically evident EBV-induced lymphopro-liferative disease achieved a prolonged remission after CTL transfusion. 44
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Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor

Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor

In recent years, other graft sources have been increasingly adopted as valid allo-HCT donor sources in the absence of an HLA-matched donor: Umbilical Cord Blood (UCB); haploidentical family donor (haplo); or HLA-misMatched Unrelated Donor (mMUD). Schlenk et al. showed that allo-HCT from an MRD or MUD significantly reduced the risk of death for patients with high-risk Acute Myeloid Leukemia (AML), defined as adverse cytogenetics and/or no response to induction therapy. Furthermore, in a prospective multicenter trial between 1998 and 2004 they observed that MRD and MUD-HCT outcomes were similar. 5 Other studies found that there was no significant difference between MRD and MUD in terms of Overall Survival (OS), relapse risk and Transplant Related Mortality (TRM). 4,19
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Photoactive Organic/Inorganic Hybrid Materials with Nanosegregated Donor-Acceptor Arrays

Photoactive Organic/Inorganic Hybrid Materials with Nanosegregated Donor-Acceptor Arrays

2 and K Si [I]. In particular, the branched terminal aliphatic chains impose a significant tilt of BTTT units in the hybrid as in the organic precursor. Furthermore, KSi [BTTT-2] and K Si [I] exhibit comparable quasi-hexagonal rectangular arrangements of POM and TBA. The predictability of the individual sub-unit organizations will facilitate the design of future generations of hybrids in view of the formation of regular nano-arrays. Preliminary photophysical studies of this D-A hybrid show that the fluorescence of the BTTT unit is considerably quenched both in solution and in the solid state owing to the formation of intramolecular charge-separated states. We anticipate that the design of such self-organized donor-acceptor POM-based hybrid could lead to a new class of multi-functional POM-based materials, easily processable, and potentially suitable for electronic and optoelectronic applications.
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Aid Effectiveness Revisited, Part 1: Optimal Discipline in Donor-Recipient Relationships

Aid Effectiveness Revisited, Part 1: Optimal Discipline in Donor-Recipient Relationships

The reaction of many donor agencies consisted of reintroducing substantial ex post conditionalities, often via the threat of witholding further tranches of aid money in case of the recipient’s non-compliance with the donor’s conditions. This implied that GBS can be suspended or reduced, such as happened with Nicaragua, for exam- ple, when the European Union and bilateral donors concluded that the government of prime minister Ortega did not want to fulfill his commitment to ensure free and fair elections in the country (Dijkstra, 2013). The World Bank, to give another example, decided to halt its budget support to the government of Honduras and to replace it with project funding after the International Monetary Fund did not renew a standby agreement (2013). More significantly, several aid agencies known for their rigor- ous approach to aid cooperation (such as SIDA in Sweden, or DFID in the United Kingdom) have begun to retreat from GBS programmes altogether, owing to serious misuses of aid resources (see the evaluation reports by SADEV, 2010, and DFID, 2011). Thus, in a review the OCDE notes that “weak systems to align with and a high risk of corruption have influenced Swedish readiness to provide general budget support” (OECD DAC, 2009, p. 47). In this context, it is not surprising that in the corridors of aid agencies a “Paris Agenda fatigue” is increasingly mentioned (Oden and Wohlgemuth, 2011). Also in line with the above diagnosis, the European Union has re-introduced the concept of result-based disbursements into its budget support programmes (part of the aid is variable, being released in successive tranches con- ditioned on the performances of the country), 2 and the World Bank has launched a new results-based lending instrument, the so-called Program-for-Results.
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Solution processable donor–acceptor oligothiophenes for bulk-heterojunction solar cells

Solution processable donor–acceptor oligothiophenes for bulk-heterojunction solar cells

polarity of solvent. There is no observable fluorescence emission upon irradiating at l abs max which is attributed to the strong charge- transfer character of these donor–acceptor oligothiophenes. These oligomers showed pronounced peak broadening and red shifts of 40 nm of absorption cutoff upon formation into thin films which is attributed to the planarization of aryl rings and the presence of interchain interactions in the solid state, resulting in the optical band gap reducing to 1.85 eV.

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The Seemingly Unrelated Dynamic Cointegration Regression Model and Testing for Purching Power Parity

The Seemingly Unrelated Dynamic Cointegration Regression Model and Testing for Purching Power Parity

Mots clés : régressions empilées, estimation efficace, parité des pouvoirs d'achat, coïntégration ABSTRACT This paper studies seemingly unrelated linear models with integrated regressors and stationary errors. By adding leads and lags of the first differences of the regressors and estimating this augmented dynamic regression model by feasible generalized least squares using the long-run covariance matrix, we obtain an efficient estimator of the cointegrating vector that has a limiting mixed normal distribution. Simulation results suggest that this new estimator compares favorably with others already proposed in the literature. We apply these new estimators to the testing of purchasing power parity (PPP) among the G-7 countries. The test based on the efficient estimates rejects the PPP hypothesis for most countries.
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Convergent structure and function of mycelial galleries in two unrelated Neotropical plant-ants

Convergent structure and function of mycelial galleries in two unrelated Neotropical plant-ants

The gallery walls of both ant species are strengthened with fungal mycelia of the order Chae- tothyriales  (Nepel et  al. 2014 ), a group of Ascomycetes which are frequently found in a[r]

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Cross-Reactive Donor-Specific CD8+ Tregs Efficiently Prevent Transplant Rejection

Cross-Reactive Donor-Specific CD8+ Tregs Efficiently Prevent Transplant Rejection

Stimulation with Bu31 Peptide Leads to Efficient CD8 + CD45RC low Treg Activation and Suppressive Function Given the low frequency of Bu31-specific cells within the total CD8 + CD45RC low Treg population, we assessed the capacity of Bu31 peptide to stimulate and increase Treg function after 6 days of incubation with syngeneic pDCs ( Figure 2 E). Bu31-stim- ulated CD8 + Tregs upregulated their secretion of interferon gamma (IFNg), an important cytokine for CD8 + Treg function ( Guillonneau et al., 2007 ), as measured in the culture supernatant ( Figure 2 E) and their expression of CD25 and CD71 as measured by flow cytome- try ( Figures 2 F and S1 A). We also observed a trend for an increase in CD28 and MHC class II expression, but no change in Foxp3 level. After 6 days of Bu31 or control peptide stimulation through the indirect pathway of recognition, CD8 + CD45RC low Tregs were recovered and tested for their suppressive capacity in a secondary coculture of effector CD4 + CD25 T cells stimulated by the direct allorecognition pathway with donor pDCs as previously described ( Picarda et al., 2014 ). In this assay, suppression depends on the efficacy of Treg pre-stimulation with peptide and relies on bystander suppression through secretion of inhibitory factors. Bu31-stimulated Tregs significantly suppressed effector T cells proliferation compared with Tregs cultured with a non-activating peptide ( Figure 2 G). Altogether, we showed Bu31 peptide effi- ciently activated CD8 + CD45RC low Tregs and potentiated their suppressive activity in vitro.
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Positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase.

Positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase.

Most of the crystal structures of GT in apo form or in complex with moenomycin A, show an unstructured or mobile region in the jaw domain between donor and acceptor sites. This region (Ser121-Gly130) located between conserved motifs 1 and 2 was proposed to have an important role in the binding of the acceptor substrate [16] . We propose that the disaccharide analogs (or lipid II) bind preferentially to the acceptor site and stabilize the mobile region which induces local structure rearrangement in the donor site increasing its affinity for moenomycin A (or the second lipid II). This mechanism may be particularly critical during the initiation stage (lipid II in the donor site). The allosteric activation of binding in the donor site could also apply to the elongating glycan chain and would play an important role in the processive elongation mechanism. Consequently, after each catalytic cycle the translo- cation of the product from the acceptor site to the donor site is concomitant with the unfolding or movement of the mobile region,
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Optimal Discipline in Donor-Recipient Relationships -Reframing the Aid Effectiveness Debate

Optimal Discipline in Donor-Recipient Relationships -Reframing the Aid Effectiveness Debate

After a few years of active implementation of the new strategy, however, donor agencies came to realize that excessive hopes had been placed in it, es- pecially when there is a wide divergence between their objectives and those of the recipient countries. In practice, indeed, the donors started budget support even when entry conditions were not met and the recipient governments just committed to or stated their intentions of improving policies, governance or public financial management. In other words, donors used GBS to bring about the desired changes in policies and governance instead of supporting deserv- ing governements (Dijkstra, 2013). A major conflict thus emerged between the objective of reducing transaction costs and engaging recipient governments by providing freely spendable money that can be used in line their own priorities, on the one hand, and the objective of influencing their policies and governance in a way considered appropriate by the donor agencies, on the other hand. The latter typically included such concerns as organizing free and fair elections, es- tablishing the rule of the law and an independent judiciary, fighting against corruption, enacting sound macroeconomic policies, and committing to poverty reduction.
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