Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report.

Hematopoietic stem cell transplantation (HSCT) is an established procedure for many acquired and congenital disorders of the hematopoietic system. A record number of 42 171 HSCT in 37 626 patients (16 030 allogeneic (43%), 21 596 autologous (57%)) were reported by 655 centers in 48 countries in 2015. Trends include continued growth in transplant activity over the last decade, with the highest percentage increase seen in middle-income countries but the highest absolute growth in the very-high-income countries in Europe. Main indications for HSCT were myeloid malignancies 9413 (25%; 96% allogeneic), lymphoid malignancies 24 304 (67%; 20% allogeneic), solid tumors 1516 (4%; 3% allogeneic) and non-malignant disorders 2208 (6%; 90% allogeneic). Remarkable is the decreasing use of allogeneic HSCT for CLL from 504 patients in 2011 to 255 in 2015, most likely to be due to new drugs. Use of haploidentical donors for allogeneic HSCT continues to grow: 2012 in 2015, a 291% increase since 2005. Growth is seen for all diseases. In AML, haploidentical HSCT increases similarly for patients with advanced disease and for those in CR1. Both marrow and peripheral blood are used as the stem cell source for haploidentical HSCT with higher numbers reported for the latter.Bone Marrow Transplantation advance online publication, 13 March 2017; doi:10.1038/bmt.2017.34

JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement.

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process

Partial reconstitution of cutaneous microvessels in long-term survivors after allogeneic bone marrow transplantation

BACKGROUND: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT) and skin is involved in acute and chronic disease. Immune-mediated vessel attack and subsequent microvessel loss have been observed in skin of patients with chronic GVHD. OBJECTIVES: To test whether long-term survivors (LTS) after allogeneic HSCT without cutaneous GVHD show signs of persistent vascular remodeling. METHODS: Microvessels in skin biopsies were investigated in a cohort of 32 LTS with a median follow-up of 17 years (range 11-26). Five were currently classified as having chronic GVHD other than skin involvement. RESULTS: LTS showed no significant difference in median microvessel density and relative vessel size distribution pattern compared to healthy controls. Past experience of GVHD and current status of chronic GVHD other than skin involvement had no impact on vessel density. In contrast, recipients with chronic cutaneous GVHD of sclerotic type and patients with lichen sclerosus have significant microvessel loss in the upper dermis. CONCLUSION: The complex therapy of allogeneic HSCT had no sustained effect on the microvascular architecture of LTS when clinicopathological evidence of cutaneous GVHD is absent. Microvascular remodeling as observed during chronic GVHD recovers completely after resolution of chronic cutaneous GVHD

Galactomannan Does Not Precede Major Signs on a Pulmonary Computerized Tomographic Scan Suggestive of Invasive Aspergillosis in Patients with Hematological Malignancies

Background. Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. Methods. In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Results. We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. Conclusions. We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of G

Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP expression in 23 +/- 4% of colonies derived from colony-forming units (CFUs) and 11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G(0) phase, which contains immature hematopoietic progenitors. Transduced fetal CD34(+) cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFP was observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation of CD34(+) cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation

Does the Constitution Provide More Ballot Access Protection for Presidential Elections Than for U.S. House Elections?

Both the U.S. Constitution and The Federalist Papers suggest that voters ought to have more freedom to vote for the candidate of their choice for the U.S. House of Representatives than they do for the President or the U.S. Senate. Yet, strangely, for the last thirty-three years, the U.S. Supreme Court and lower courts have ruled that the Constitution gives voters more freedom to vote for the candidate of their choice in presidential elections than in congressional elections. Also, state legislatures, which have been writing ballot access laws since 1888, have passed laws that make it easier for minor-party and independent candidates to get on the ballot for President than for the U.S. House. As a result, voters in virtually every state invariably have far more choices on their general election ballots for the President than they do for the House. This Article argues that the right of a voter to vote for someone other than a Democrat or a Republican for the House is just as important as a voter’s right to do so for President, and that courts should grant more ballot access protection to minor-party and independent candidates for the House

Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

AbstractDonor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P 50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD

Human metapneumovirus infection after allogeneic hematopoietic stem cell transplantation

Background: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection. Methods: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL). Results: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5% (1/8). Conclusions: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infectio

Latin America: the next region for haematopoietic transplant progress

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009–2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5–8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3–4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America