An Analysis of the Worldwide Utilization of Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Tokaz, Molly C.

; Baldomero, Helen ; Cowan, Andrew J. ; Saber, Wael ; Greinix, Hildegard ; Koh, Mickey B.C. ; Kröger, Nicolaus ; Mohty, Mohamad

; Galeano, Sebastian

; Okamoto, Shinichiro ; Chaudhri, Naeem ; Karduss, Amado J. ; Ciceri, Fabio ; Colturato, Vergílio Antonio R. ; Corbacioglu, Selim ; Elhaddad, Alaa ; Force, Lisa M. ; Frutos, Cristóbal ; León, Andrés Gómez-De ; Hamad, Nada

; Hamerschlak, Nelson ; He, Naya ; Ho, Aloysius ; Huang, Xiao-jun ; Jacobs, Ben ; Kim, Hee-Je ; Iida, Minako ; Lehmann, Leslie ; de Latour, Regis Peffault ; Percival, Mary-Elizabeth M. ; Perdomo, Martina ; Rasheed, Walid ; Schultz, Kirk R. ; Seber, Adriana ; Ko, Bor-Sheng ; Simione, Anderson João ; Srivastava, Alok ; Szer, Jeff ; Wood, William A. ; Kodera, Yoshihisa ; Nagler, Arnon ; Snowden, John A. ; Weisdorf, Daniel ; Passweg, Jakob ; Pasquini, Marcelo C. ; Sureda, Anna ; Atsuta, Yoshiko ; Aljurf, Mahmoud ; Niederwieser, Dietger

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Acute myeloid leukemia (AML) has an aggressive course and a historically dismal prognosis. For many patients, hematopoietic stem cell transplantation (HSCT) represents the best option for cure, but access, utilization, and health inequities on a global scale remain poorly elucidated. We wanted to describe patterns of global HSCT use in AML for a better understanding of global access, practices, and unmet needs internationally. Estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease 2019 study. HSCT activities were collected from 2009 to 2016 by the Worldwide Network for Blood and Marrow Transplantation through its member organizations. The pri-mary endpoint was global and regional use (number of HSCT) and utilization of HSCT (number of HSCT/number of incident cases) for AML. Secondary outcomes included trends from 2009 to 2016 in donor type, stem cell source, and remission status at time of HSCT. Global AML incidence has steadily increased, from 102,000 (95% uncertainty interval: 90,200-108,000) in 2009 to 118,000 (104,000-126,000) in 2016 (16.2%). Over the same period, a 54.9% increase from 9659 to 14,965 HSCT/yr was observed globally, driven by an increase in allogeneic (64.9%) with a reduction in autologous (-34.9%) HSCT. Although the highest numbers of HSCT continue to be performed in high-resource regions, the largest increases were seen in resource-constrained regions (94.6% in Africa/East Mediterra-nean Region [AFR/EMR]; 34.7% in America-Nord Region [AMR-N]). HSCT utilization was skewed toward high-resource regions (in 2016: AMR-N 18.4%, Europe [EUR] 17.9%, South-East Asia/Western Pacific Region [SEAR/WPR] 11.7%, America-South Region [AMR-S] 4.5%, and AFR/EMR 2.8%). For patients <70 years of age, this difference in uti-lization was widened; AMR-N had the highest allogeneic utilization rate, increasing from 2009 to 2016 (30.6% to 39.9%) with continued low utilization observed in AFR/EMR (1.7% to 2.9%) and AMR-S (3.5% to 5.4%). Across all regions, total HSCT for AML in first complete remission (CR1) increased (from 44.1% to 59.0%). Patterns of donor stem cell source from related versus unrelated donors varied widely by geographic region. SEAR/WPR had a 130.2% increase in related donors from 2009 to 2016, and >95% HSCT donors in AFR/EMR were related; in comparison, AMR-N and EUR have a predilection for unrelated HSCT. Globally, the allogeneic HSCT stem cell source was predom-inantly peripheral blood (69.7% of total HSCT in 2009 increased to 78.6% in 2016). Autologous HSCT decreased in all regions from 2009 to 2016 except in SEAR/WPR (18.9%). HSCT remains a central curative treatment modality in AML. Allogeneic HSCT for AML is rising globally, but there are marked variations in regional utilization and practices, including types of graft source. Resource-constrained regions have the largest growth in HSCT use, but utilization rates remain low, with a predilection for familial-related donor sources and are typically offered in CR1. Further studies are necessary to elucidate the reasons, including economic factors, to understand and address these health inequalities and improve discrepancies in use of HSCT as a potentially curative treatment globally.

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