ALBERT

Description: The TEL gene on 12p12-13 is a target for a number of translocations associated with various hematological malignancies. The fusion of the TEL gene to the Sykgene in a patient with myelodysplastic syndrome (MDS) with t(9;12)(q22;p12) is reported. Southern blot analysis of patient bone marrow cells with TEL and Syk gene probes detected rearranged fragments. Anchored polymerase chain reaction identified the Syk gene, a nonreceptor tyrosine kinase, on 9q22 fused downstream of TEL exon 5. The TELgene was fused in-frame to Syk and produced a fusion protein that was constitutively phosphorylated in tyrosine with dimerization that was mediated by the helix-loop-helix domain of TEL. A TEL-Syk fusion product transformed the murine hematopoietic cell line BaF3 to interleukin-3 growth factor independence. TEL-Syk is a novel transforming protein and leads to the transformation of hematopoietic cells. These data implicate that the rearranged Syk gene is involved in the pathogenesis of hematopoietic malignancies.

Description: Since the first report by Nobel laureate, the late E. Donnall Thomas (NEJM, 1957, 257), HSCT has developed from an experimental to an established curative treatment for many congenital or acquired disorders of the hematopoietic system. The key steps of this success story are linked to progress in tissue typing, donor selection, supportive care and immunosuppression and fostered by intensive collaboration of physicians around the world through outcome and donor registries. The WBMT, a federation and official Non-governmental Organization of the World Health Organization, has collected HSCT activity data from its member societies and from national registries not part of an international HSCT society. Data collection did include the first transplants by ED Thomas and the first global report by M. Bortin (Transplantation 1970, 571). European data were derived from the Med A form of the European Group for Blood and Marrow Transplantation-EBMT for the years 1965-1989 and from the annual activity survey since 1990. Non-European data back to 1969 were provided by the Center for International Blood and Marrow Transplant Research-CIBMTR, with additional recent data provided by the Asia-Pacific Blood and Marrow Transplantation Group (APBMT, since 1974), the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR, since 1980), the Eastern Mediterranean Blood and Marrow Transplantation Group (EMBMT, since 1984), the Canadian Blood and Marrow Transplantation Group (CGBMT, since 2002), the Latin American Blood and Marrow Transplantation Group (LABMT, since 2009) and the African Blood and Marrow Transplant Group (AFBMT, since 2010). Double reporting was minimized by crosschecking registries and unrelated donations. Missing data from a few regions in 2012 were extrapolated from previous years assuming a 5% increase. As of December 2012, the 1450 transplant centers from 72 countries over 5 continents had reported 1.000.000 HSCT (58% autologous, 42% allogeneic). The dramatic recent increase in rate of utilization of HSCT is illustrated by the fact that there were 10.000 HSCTs worldwide by 1985, 50.000 by 1990, 100.000 by 1994, 500.000 by 2004 and 1.000.000 by December 2012. The absolute and relative contribution differed significantly with Europe providing 53%, the Americas 31%, Australasia 14% and Eastern-Mediterranean and Africa 2% to the total HSCT number (allogeneic HSCT: 45%, 32%, 20% and 3%; autologous HSCT: 58%, 31%, 10% and 1%). The increase in activity has been almost linear over the past 55 years with two exceptions, a decrease in autologous HSCT for breast cancer from 1999 especially in the Americas and a decrease in allogeneic HSCT for CML after 2000 seen everywhere except in the Eastern-Mediterranean/African region. The rise in HSCT numbers during the last decade was mainly due to an increase in allogeneic HSCT from unrelated donors; the relative increase being highest in Australasia. Recent growth was primarily due to increases in activity in existing transplant centers, rather than in the number of transplant centers. The main indications for autologous HSCT today are lymphoproliferative disorders 87% (myeloma 46% and lymphoma 41%), solid tumors 8.6% and AML 2.75%; for allogeneic HSCT leukemias 73% (AML 34.6%; ALL 16.8%; CML 4%; myelodysplastic and myeloproliferative disorders 13.3%; CLL 2.9% and other leukemias 1%), lymphoproliferative disorders 14.3% and bone marrow failure syndromes 5.5%. In 2010, cord blood was used as stem cell source in 19% of unrelated HSCT. These data were compiled through collaboration of the global HSCT community. Global collaboration has also been essential for the diffusion of HSCT as a therapy and especially for unrelated HSCT. More than 22 million unrelated donors are available today from a global network (World Marrow Donor Association, WMDA) of donor registries and cord blood banks and about 30% of unrelated HSCT involve a donor and recipient in different countries. The success of HSCT serves as a model for organ repair by the use of healthy stem cells and as a model for global cooperation in meeting the needs of an international patient population. These data also illustrate the challenges for the global medical community in providing state of the art care in regions with constrained resources and the need to find ways to make the therapy more available in order to provide better outcomes for patients with life-threatening but potentially curable diseases. Disclosures: Gluckman: Cord use: Honoraria; gamida: Honoraria.

Description: Abstract 1016 Transplantation of cells, tissues and organs is recognized by the World Health Organization (WHO) as a global task, no longer restricted to affluent countries. Still, there are few data relating to its use and trends on a global level and the macroeconomic factors associated with it. Data from 146,808 patients (pts) with hematopoietic stem cell transplantations (HSCT), 66,226 allogeneic (allo 45%), 80,582 autologous (auto 55%) from 1407 centers in 70 countries were used to describe the current status and to analyze trends over the period from 2006 to 2008. Transplant rates (TR, number of HSCT/10 million inhabitants) and their changes from 2006 to 2008 were assessed by main indication and donor type (leukemias (52,322 pat (36%), 47,674 allo, 4,648 auto); lymphoproliferative disorders (77,237 pts (53%), 9,846 allo, 67,391 auto); solid tumors (8,057 pat (5%), 399 allo, 7,658 auto) and non-malignant disorders and others (9,192 pts (6%), 8,307 allo, 885 auto) for each participating country and its corresponding WHO region America (42,470 pts (29%), 19,463 allo, 23,007 auto), Asia (including South-East Asia and Western Pacific) (25,931 pts (18%), 15,547 allo, 10,384 auto), Eastern-Mediterranean/Africa (3,986 pat (3%), 2,509 allo, 1,477 auto) and Europe (74,421 pat (51%), 28,707 allo, 45,714 auto). The associations of TR with Gross National Income per Capita (GNI/cap) and, for unrelated donor HSCT, with presence or absence of an unrelated donor registry were calculated by linear regression analyses. Proportions of donor type (p