A tool for clarifying expectations in undergraduate research experiences.

Articulating clear and achievable expectations is fundamental to both education and organizational management. In this article, we provide a simple intervention for clarifying expectations-and establishing that these expectations have been understood-which proved beneficial both to community college interns and to their internship mentors in biotech-related undergraduate research experiences. Internship mentors were asked to utilize a simple Expectation Clarity Tool to outline the expectations, success metrics, baseline assessments, and training strategy and support that would be foundational to their intern's project. These included expectations around conceptual, technical, performance, and professional skills and behaviors. Concurrently, but independently, community college interns were asked to complete the same type of exercise as a way of identifying gaps in their knowledge and understanding of their mentor's expectations and their internship project. The mentor's completed Expectation Clarity Tool was then shared with their intern. As a result of completing this relatively simple intervention, the majority of mentors reported that it increased their confidence as a mentor, taught them a new mentoring skill, changed how they will mentor trainees moving forward, and positively impacted their relationship with their trainee. On the intern side, the majority of interns reported that engaging in this intervention, both as an independent exercise and in obtaining their mentor's completed Expectation Clarity Tool, increased their confidence as an intern and positively impacted the success of their internship.

Reduced-toxicity myeloablative conditioning regimen using fludarabine and full doses of intravenous busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens: Results of a multicenter prospective phase 2 trial.

Data regarding the safety and efficacy of reduced-toxicity conditioning regimen (RTC) prior to allogeneic stem cell transplantation (allo-SCT) to treat hematological malignancies in pediatric patients are limited. This prospective multicenter, phase 2 trial investigated a RTC regimen based on the combination of intravenous busulfan (3.2 mg/kg/d x 4 days), fludarabine (30 mg/m2/d x 5 days) and antithymocyte globulin (Thymoglobulin®, Genzyme; 5 mg/kg total dose) with the aim of delivering high dose myeloablation that would allow optimal disease control while minimizing toxicity, in a subgroup of children at very high risk of non-relapse mortality (NRM). The primary endpoint was NRM at 1 year after allo-SCT. A total of 48 high risk patients were included (median age, 13 years; range, 3-24). At 1 year, the cumulative incidence of recurrence/disease progression and NRM were 33% and 8%, respectively. With a median follow-up of 23 months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) at 1 year were 69% and 58%, respectively. We conclude that the RTC regimen used in this prospective trial is safe, with a < 10% NRM rate noted among high-risk children and adolescents, paving the way for larger phase 3 trials incorporating novel agents pre- and post-allo-SCT.(ClinicalTrials.gov Identifier: NCT01572181).

VANDA regimen followed by blinatumomab leads to favourable outcome in patients with Philadelphia chromosome-negative B-precursor acute lymphoblastic leukaemia in first relapse.

Adults with relapsed or refractory B-precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have very poor outcome. Blinatumomab as single agent has shown activity in R/R BCP-ALL. We aimed to assess the activity of blinatumomab in concomitant association with intensive chemotherapy. Seventeen patients with R/R BCP-ALL were treated with combination of blinatumomab and VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone and asparaginase) regimen. Complete remission (CR) was achieved in 14/17 patient (82%) and 11/17 (65%) were transplanted. One-year leukaemia-free survival was 58.8% for the whole cohort and 90.9% for transplanted patients. These preliminary data suggest that the VANDA-blinatumomab salvage regimen leads to a very high rate of CR and HSCT in suitable patients.

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.

BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).

Reduced-Intensity versus Myeloablative Conditioning in Cord Blood Transplantation for Acute Myeloid Leukemia (40-60 years) across Highly Mismatched HLA Barriers-On Behalf of Eurocord and the Cellular Therapy & Immunobiology Working Party (CTIWP) of EBMT.

The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P = .9), NRM (HR, 0.68; P = .2), and relapse (HR, 1.24; P = .5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen.

The Academic Career Readiness Assessment: Clarifying Hiring and Training Expectations for Future Biomedical Life Sciences Faculty.

We describe here the development and validation of the Academic Career Readiness Assessment (ACRA) rubric, an instrument that was designed to provide more equity in mentoring, transparency in hiring, and accountability in training of aspiring faculty in the biomedical life sciences. We report here the results of interviews with faculty at 20 U.S. institutions that resulted in the identification of 14 qualifications and levels of achievement required for obtaining a faculty position at three groups of institutions: research intensive (R), teaching only (T), and research and teaching focused (RT). T institutions hire candidates based on teaching experience and pedagogical practices and ability to serve diverse student populations. RT institutions hire faculty on both research- and teaching-related qualifications, as well as on the ability to support students in the laboratory. R institutions hire candidates mainly on their research achievements and potential. We discuss how these hiring practices may limit the diversification of the life science academic pathway.

The Supervisory Role of Life Science Research Faculty: The Missing Link to Diversifying the Academic Workforce?

In addition to developing innovative research programs, life science research faculty at research-intensive institutions are tasked with providing career mentoring and scientific training to new generations of scientists, including postgraduate, graduate, and undergraduate students. In this essay, we argue for a redefinition of mentoring in laboratory research, to thoroughly distinguish three essential roles played by research faculty relative to their trainees: advisor, educator, and supervisor. In particular, we pay attention to the often unacknowledged and misunderstood role of a faculty member as a supervisor and discuss the impact of neglecting supervisory best practices on trainees, on the diversity of the academic pipeline, and on the research enterprise. We also provide actionable frameworks for research mentors who wish to use inclusive supervisory and pedagogical practices in their laboratory. Finally, we call for more research around the supervisory role of research faculty and its impact on trainees, particularly community college students, in order to help broaden the participation of underrepresented students in STEM fields.

Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC).

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.

Similar outcome of allogeneic stem cell transplantation after myeloablative and sequential conditioning regimen in patients with refractory or relapsed acute myeloid leukemia: A study from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire.

Patients with acute myeloid leukemia (AML) in relapse or refractory to induction therapy have a dismal prognosis. Allogeneic hematopoietic stem cell transplantation is the only curative option. In these patients, we aimed to compare the results of a myeloablative transplant versus a sequential approach consisting in a cytoreductive chemotherapy followed by a reduced intensity conditioning regimen and prophylactic donor lymphocytes infusions. We retrospectively analyzed 99 patients aged 18-50 years, transplanted for a refractory (52%) or a relapsed AML not in remission (48%). Fifty-eight patients received a sequential approach and 41 patients a myeloablative conditioning regimen. Only 6 patients received prophylactic donor lymphocytes infusions. With a median follow-up of 48 months, 2-year overall survival was 39%, 95% confidence interval (CI) (24-53) in the myeloablative group versus 33%, 95% CI (21-45) in the sequential groups (P = .39), and 2-year cumulative incidence of relapse (CIR) was 57% versus 50% respectively (P = .99). Nonrelapse mortality was not higher in the myeloablative group (17% versus 15%, P = .44). In multivariate analysis, overall survival, CIR and nonrelapse mortality remained similar between the two groups. However, in multivariate analysis, sequential conditioning led to fewer acute grade II-IV graft versus host disease (GVHD) (HR for sequential approach = 0.37; 95% CI: 0.21-0.65; P < .001) without a significant impact on chronic GVHD (all grades and extensive). In young patients with refractory or relapsed AML, myeloablative transplant and sequential approach offer similar outcomes except for a lower incidence of acute GvHD after a sequential transplant.

Extracorporeal photopheresis for GVHD prophylaxis after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation: a prospective multicenter phase 2 study.

We performed a prospective multicenter phase 2 study to evaluate the safety and efficacy of prophylactic Extracorporeal Photopheresis (ECP) in adult patients with hematological malignancies early after RIC allo-HSCT on day 21 twice per week during the first two weeks and then once per week for the next four weeks for a total of eight ECP courses. A total of 20 patients were included; 10 were males, median age was 60 years. All patients engrafted, 17 (85%) received the total eight ECP courses. There were no adverse effects related to ECP. Seven patients developed acute graft-versus-host disease (GVHD), with 15% grade ≥ II cumulative incidence at day 100. The cumulative incidence of chronic GVHD at 2 years was 22%. The 2 years probability of overall survival (OS) and progression-free survival (PFS) were 84 and 74%, respectively. This study shows encouraging results with low acute and chronic GVHD incidence and no interference with graft-versus-leukemia (GVL) effect.

Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). METHODS: Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. RESULTS: One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. CONCLUSIONS: Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.

High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia - an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.

External and Internal Barriers to Studying Can Affect Student Success and Retention in a Diverse Classroom.

Although a majority of under-represented minority (URM) students begin their postsecondary education at community colleges, little is known about barriers to success and retention for transfer-bound science students. This study focuses on some of the barriers that affect these students' ability to study adequately for a community college "gateway" course. It tests whether instructors' expectations of study time were realistic for community college students and whether students reported facing external barriers, such as job and family responsibilities, or internal barriers to studying, such as lack of motivational, cognitive, and metacognitive abilities, all of which have been shown to impact academic success and retention. It also tests whether students who faced such barriers were less likely to succeed in and complete the course, as well as whether time spent studying was related to course success. The findings reported here show that community college students do not have enough available time to study and that external and internal barriers are both prevalent among these students. In addition, students who faced such barriers are more likely to fail or drop the class. Results also show that study time is positively correlated with retention, but not performance, as well as with some motivational, cognitive, and metacognitive dimensions of self-regulated learning. These findings lead to new questions, including whether student success in a community college class is associated with the use of cognitive and metacognitive learning strategies for students with no prior degrees, and whether increased course structure may improve success for college students with lower self-regulated abilities.

Adenovirus-specific T-cell Subsets in Human Peripheral Blood and After IFN-γ Immunomagnetic Selection.

Adoptive antiviral cellular immunotherapy by infusion of virus-specific T cells (VSTs) is becoming an alternative treatment for viral infection after hematopoietic stem cell transplantation. The T memory stem cell (TSCM) subset was recently described as exhibiting self-renewal and multipotency properties which are required for sustained efficacy in vivo. We wondered if such a crucial subset for immunotherapy was present in VSTs. We identified, by flow cytometry, TSCM in adenovirus (ADV)-specific interferon (IFN)-γ+ T cells before and after IFN-γ-based immunomagnetic selection, and analyzed the distribution of the main T-cell subsets in VSTs: naive T cells (TN), TSCM, T central memory cells (TCM), T effector memory cell (TEM), and effector T cells (TEFF). In this study all of the different T-cell subsets were observed in the blood sample from healthy donor ADV-VSTs, both before and after IFN-γ-based immunomagnetic selection. As the IFN-γ-based immunomagnetic selection system sorts mainly the most differentiated T-cell subsets, we observed that TEM was always the major T-cell subset of ADV-specific T cells after immunomagnetic isolation and especially after expansion in vitro. Comparing T-cell subpopulation profiles before and after in vitro expansion, we observed that in vitro cell culture with interleukin-2 resulted in a significant expansion of TN-like, TCM, TEM, and TEFF subsets in CD4IFN-γ T cells and of TCM and TEM subsets only in CD8IFN-γ T cells. We demonstrated the presence of all T-cell subsets in IFN-γ VSTs including the TSCM subpopulation, although this was weakly selected by the IFN-γ-based immunomagnetic selection system.

Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies.

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT.

Effect of graft source on unrelated donor hemopoietic stem cell transplantation in adults with acute myeloid leukemia after reduced-intensity or nonmyeloablative conditioning: a study from the Société Francaise de Greffe de Moelle et de Thérapie Cellulaire.

This retrospective report compared the 4-year outcomes of allogeneic stem cell transplantation (allo-SCT) in 651 adult patients with acute myeloid leukemia receiving a reduced-intensity (RIC) or nonmyeloablative conditioning (NMA) regimen according to the type of unrelated donors. These were either umbilical cord blood (UCB, n = 205), a 9/10 mismatched unrelated donor (MisMUD, n = 99), or a 10/10 matched unrelated donor (MUD, n = 347) graft. Neutrophil recovery was slower in UCB (74.5% by day 42) compared with MisMUD (94.8%) and MUD (95.6%) (P < .001). There was no significant difference in nonrelapse mortality between UCB and both MUD (hazard ratio [HR], 1.05; 95% confidence interval [CI], .62 to 1.78; P = .85) and MisMUD (HR, 1.58; 95% CI, .88 to 2.83; P = .13) The relapse/progression was similar between UCB and MisMUD (HR, .62; 95% CI, .37 to 1.03; P = .07), but was significantly lower in MUD compared with UCB (HR, .60; 95% CI, .39 to .92; P = .02). The rate of extensive chronic graft-versus-host disease (GVHD) was similar between UCB and both MUD (HR, 2.15; 95% CI, .93 to 4.97; P = .08) and MisMUD (HR, 1.84; 95% CI, .68 to 4.95; P = .23). The rate of severe grade III and IV acute GVHD was significantly increased in MisMUD compared with UCB (HR, 2.61; 95% CI, 1.30 to 5.23; P = .007). There was no significant difference in overall survival between UCB and both MisMUD (HR, .98; 95% CI, .66 to 1.45; P = .92) and MUD (HR, .74; 95% CI, .52 to 1.03; P = .08). These data suggest that in the setting of RIC/NMA, allo-SCT UCB is a valid alternative graft source, with significantly less chronic GVHD, compared with MisMUD, when there is no MUD available or when urgent transplantation is needed.

Decreased nonrelapse mortality after unrelated cord blood transplantation for acute myeloid leukemia using reduced-intensity conditioning: a prospective phase II multicenter trial.

A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).

Antithymocyte globulin before allogeneic stem cell transplantation for progressive myelodysplastic syndrome: a study from the French Society of Bone Marrow Transplantation and Cellular Therapy.

We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n = 153) or HLA-matched unrelated (n = 89). Patients received blood (n = 90) or marrow (n = 152) grafts after either myeloablative (n = 109) or reduced-intensity (n = 133) conditioning. Three-year overall and event-free survival, nonrelapse mortality, relapse, and chronic graft-versus-host disease (GVHD) development were not significantly different between the 2 groups. In contrast, acute grade II to IV GVHD occurred more often in the no-ATG group (55% of the patients) than in the ATG group (27%, P < .0001). Similar results were observed with acute grade III to IV GVHD (28% and 14% in the no-ATG group and ATG group, respectively; P = .009). In multivariate analysis, after adjustment with propensity score, the absence of ATG was the strongest parameter associated with an increased risk of acute grade II to IV GVHD (hazard ratio, 2.13; 95% confidence interval, 1.35 to 3.37; P = .001]. ATG had no impact on overall and event-free survival or cumulative incidence of the relapse. In conclusion, the addition of ATG to allo-SCT conditioning did not increase the incidence of relapse of patients with progressive MDS. The incidence of acute GVHD was decreased without compromising outcomes.