Aids given to beginning teachers in Rhode Island: their source and their usefulness.

Thesis (Ed.M.)--Boston Universit

Measurement of ϒ production in pp collisions at √s = 2.76 TeV

The production of ϒ(1S), ϒ(2S) and ϒ(3S) mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 pb−1 collected in proton–proton collisions at a centre-of-mass energy of √s = 2.76 TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the ϒ transverse momentum and rapidity, over the ranges pT < 15 GeV/c and 2.0 < y < 4.5. The total cross-sections in this kinematic region, assuming unpolarised production, are measured to be σ (pp → ϒ(1S)X) × B ϒ(1S)→μ+μ− = 1.111 ± 0.043 ± 0.044 nb, σ (pp → ϒ(2S)X) × B ϒ(2S)→μ+μ− = 0.264 ± 0.023 ± 0.011 nb, σ (pp → ϒ(3S)X) × B ϒ(3S)→μ+μ− = 0.159 ± 0.020 ± 0.007 nb, where the first uncertainty is statistical and the second systematic

Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy–based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor–based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P 5 .15), leukemia-free survival (P 5 .50), nonrelapse mortality (P 5 .16), relapse (P 5 .90), or grade II-IV acute GVHD (P 5 .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P, .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease–donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy–based Haplo-HCT vs MSD using calcineurin inhibitor–based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients. © 2019 American Society of Hematology. All rights reserved

Allogeneic Transplantation to Treat Therapy Related MDS and AML in Adults.

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. Therefore, the Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions and more effective anti-neoplastic approaches before and after allo-HCT. BACKGROUND Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. OBJECTIVES The primary objectives are OS and DFS. The secondary objectives are non-relapse mortality (NRM), relapse, GVHD rates and identifying prognostic factors for outcomes after allo-HCT. STUDY DESIGN The Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Cumulative incidence function was used to estimate relapse, NRM, acute and chronic GVHD. Kaplan-Meier estimate was used to calculate probabilities of OS and DFS. Cox proportional hazards regression model was used to estimate hazard ratio (HR) of patient / disease / transplant related factors for outcomes of interest. RESULTS The median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). CONCLUSIONS Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions. Through better patient optimization, more effective conditioning and studies of post-HCT interventions, outcomes for patients with t-MDS and t-AML may improve

Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation:a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia. To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative acute lymphoblastic leukemia in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. Patients with abnormal cytogenetics had 40% leukemia-free survival and 42% overall survival at 5-years post-transplant, which was similar to those with normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (p=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse (hazard ratio=2.11; 95% confidence interval, 1.04-4.27) and treatment failure (hazard ratio=1.97; 1.20-3.24). Complex karyotype was prognostic for relapse (hazard ratio=1.69; 1.06-2.69), whereas t(8;14) predicted treatment failure (hazard ratio=2.85; 1.35-6.02) and overall mortality (hazard ratio=3.03; 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse (monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy), intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (p=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities of acute lymphoblastic leukemia can be overcome by transplant, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes

Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR

Survival following allogeneic transplant in patients with myelofibrosis.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up