Global Hematopoietic Stem Cell Transplantation (HSCT) At One Million: An Achievement Of Pioneers and Foreseeable Challenges For The Next Decade. A Report From The Worldwide Network For Blood and Marrow Transplantation (WBMT)
Authors: Niederwieser Dietger , Pasquini Marcelo C , Aljurf Mahmoud D. , Confer Dennis L. , Baldomero Helen , Bouzas Luis Fernando , Horowitz Mary M. , Iida Minako , Kodera Yoshihisa , Lipton Jeffrey H. , Oudshoorn Machteld , Gluckman Eliane , Passweg Jakob R. , Szer Jeffrey , Novitzky Nicolas , van Rood Jon J. , Noel Luc , Madrigal J. Alejandro , Frauendorfer Karl , Gratwohl Alois , Appelbaum Frederick R. 
Published: October 2019

Abstract
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.