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Figure.
Correlation Between Stem Cell Source and National Income
Correlation Between Stem Cell Source and National Income

There were 49 countries with more than 5 hematopoietic stem cell transplantations for bone marrow failure between 2009 and 2010 according to World Health Organization regions. Each data marker represents the proportion of bone marrow as stem cell source and gross national income per capita in each country. Association of these variables was estimated by linear regression analysis using the least-squares method. Taiwan and Argentina were excluded from the analysis because of the lack of data about gross national income per capita.

Table.  
Source of Stem Cells for Allogeneic Hematopoietic Stem Cell Transplantations for Bone Marrow Failure According to World Health Organization (WHO) Regions
Source of Stem Cells for Allogeneic Hematopoietic Stem Cell Transplantations for Bone Marrow Failure According to World Health Organization (WHO) Regions
1.
Sureda  A, Bader  P, Cesaro  S,  et al.  Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50(8):1037-1056.
PubMedArticle
2.
Gratwohl  A, Baldomero  H, Gratwohl  M,  et al; Worldwide Network of Blood and Marrow Transplantation (WBMT).  Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study. Haematologica. 2013;98(8):1282-1290.
PubMedArticle
3.
Eapen  M, Le Rademacher  J, Antin  JH,  et al.  Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood. 2011;118(9):2618-2621.
PubMedArticle
4.
Scheinberg  P, Young  NS.  How I treat acquired aplastic anemia. Blood. 2012;120(6):1185-1196.
PubMedArticle
5.
Gratwohl  A, Baldomero  H, Aljurf  M,  et al; Worldwide Network of Blood and Marrow Transplantation.  Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303(16):1617-1624.
PubMedArticle
Research Letter
January 12, 2016

Global Use of Peripheral Blood vs Bone Marrow as Source of Stem Cells for Allogeneic Transplantation in Patients With Bone Marrow Failure

Author Affiliations
  • 1Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
  • 2European Society for Blood and Marrow Transplantation Transplant Activity Survey Office, University Hospital, Basel, Switzerland
  • 3Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee
  • 4Australasian Bone Marrow Transplant Recipient Registry, Royal Melbourne Hospital, Parkville, Australia
  • 5Hematology-Oncology Department, University Hospital, Leipzig, Germany
  • 6Asia Pacific Blood and Marrow Transplant Group Data Centre Nagakute Campus, Aichi Medical University, School of Medicine, Nagakute, Japan
JAMA. 2016;315(2):198-200. doi:10.1001/jama.2015.13706

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many patients with bone marrow failure.1 Bone marrow was initially the only stem cell source available until the 1990s when peripheral blood stem cells (PBSCs) and cord blood began to be used.

Currently, PBSCs are the major stem cell source,2 owing to faster engraftment and ease of collection despite a higher rate of graft-vs-host disease and lower survival rates in patients with nonmalignant disorders.3

Therefore, bone marrow is currently recommended for HSCT in patients with bone marrow failure.4 The objectives of this study were to investigate the use of PBSCs and bone marrow as stem cell sources for HSCT in patients with bone marrow failure worldwide and to identify potential factors associated with the use of each stem cell source.

Methods

Data from retrospective HSCT surveys by the Worldwide Network for Blood and Marrow Transplantation were used.5 International and regional organizations collect the numbers of transplants annually by disease, donor type, and stem cell source from countries known to perform HSCT in World Health Organization (WHO) member states.5

Most data are from transplant registries; for countries without registries, transplant centers were contacted directly. We estimate that the data cover more than 90% of all transplants performed. No individual patient data were used and no ethics committee approval was mandated as per Swiss legal requirements.

We divided countries into 4 WHO regions and focused on allogeneic HSCTs for bone marrow failure performed in 2009 and 2010. Categorical variables (World Bank income categories, WHO regions, and stem cell sources) were compared using the χ2 test.

The association between gross national income (GNI) per capita in $US and stem cell sources was analyzed using linear regression. Goodness of fit was measured using the coefficient of determination (R2). All P values were 2-sided and those less than .05 were considered significant. Statistical analysis was performed using SPSS version 20.0 (SPSS Inc).

Results

Among 194 WHO member states, 84 perform HSCT and 74 reported at least 1 HSCT during 2009 through 2010. Among 114 217 HSCTs reported by 1482 transplant teams, 3282 allogeneic HSCTs were performed for bone marrow failure (Table). Donor type and stem cell source differed between regions.

Use of unrelated donors was highest in Europe (515/1107; 47%); use of matched sibling donors was highest in the Eastern Mediterranean region and Africa (249/274; 91%). Of the 3282 allogeneic HSCTs, the stem cell sources were bone marrow (1766; 54%), PBSC (1336; 41%), and cord blood (180; 5%).

Excluding cord blood, bone marrow was used in 1766 (57%) of the remaining 3102 HSCTs, with no difference between family and unrelated donors. Bone marrow was used most commonly in the Americas (631/843; 75%) and in Europe (632/1057; 60%), but not in the Eastern Mediterranean region and Africa (123/266; 46%) and in the Asia Pacific region (380/936; 41%; excluding Japan, 19%) (χ2P < .001 comparing the 4 regions).

The use of bone marrow increased from 20% in countries with low and low-middle incomes to 50% with high-middle incomes to 64% with high incomes (P < .001). The GNI per capita and stem cell source had a weak but significant association (R2 = 0.2, P = .002; Figure).

Discussion

This study showed that the stem cell source used for HSCT for bone marrow failure varied worldwide, with PBSCs being used more frequently in regions with limited resources. Most likely PBSCs are still used, despite disadvantages in patients with bone marrow failure, because centers obtain PBSCs routinely for other indications and cell separators are available at any transplant center. These cells are associated with rapid engraftment, a cost-reducing benefit.

By contrast, bone marrow harvest requires trained physicians, specific equipment, and hospitalization of the donor. The correlations with GNI per capita support the hypothesis that short-term financial considerations are important.

This study has limitations. Participation was voluntary. Some countries had no formal data quality control. There were a limited number of HSCT cases in low-income countries, leading to weak correlations between stem cell source and GNI per capita.

National and international transplant organizations and authorities should foster regional-accredited bone marrow harvest centers for patients with nonmalignant disorders and provide resources to establish such infrastructures. Unrelated donor registries should provide information on the necessity of bone marrow donation for patients with bone marrow failure.

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Article Information
Section Editor: Jody W. Zylke, MD, Deputy Editor.

Corresponding Author: Ayami Yoshimi, MD, PhD, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany (ayami.yoshimi@uniklinik-freiburg.de).

Author Contributions: Dr Yoshimi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Gratwohl and Kodera contributed equally.

Study concept and design: Yoshimi, Horowitz, Niederwieser, Gratwohl, Kodera.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Yoshimi, Baldomero, Gratwohl.

Critical revision of the manuscript for important intellectual content: Horowitz, Szer, Niederwieser, Kodera.

Obtained funding: Kodera.

Administrative, technical, or material support: Baldomero, Niederwieser, Kodera.

Study supervision: Horowitz, Niederwieser, Gratwohl, Kodera.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Szer reported receiving grants and personal fees from Alexion Pharmaceuticals Australia Pty Ltd. Dr Niederwieser reported receiving grants from and serving on the speaker’s bureau for Novartis; and serving on the speaker’s bureau for Bristol-Myers Squibb. No other disclosures were reported.

Funding/Support: Funding for this study was indirectly provided by the funders of the Worldwide Network of Blood and Marrow Transplantation (WBMT).

Role of the Funder/Sponsor: The WBMT had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: In addition to those authors listed in the byline, the WBMT investigators were Peter Noellke (University of Freiburg, Freiburg, Germany), Michael Gratwohl, PhD (University of St Gallen, St Gallen, Switzerland), Jakob Passweg, MD (European Group for Blood and Marrow Transplantation [EBMT] Transplant Activity Survey Office, University Hospital Basel, Basel, Switzerland), Mahmoud Aljurf, MD (Eastern Mediterranean Blood and Marrow Transplant Group, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia), Yoshiko Atsuta, MD (Asia Pacific Blood and Marrow Transplant Group [APBMT] Data Center, Nagoya Campus, Nagoya University, Nagoya, Japan), Minako Iida, MD (APBMT Data Center, Aichi Medical University, School of Medicine, Nagakute, Japan), Luis Fernando Bouzas, MD (Latin American Blood and Marrow Transplantation, Instituto Nacional de Cancer, Rio de Janeiro, Brazil), Jeff Lipton, MD (Canadian Blood and Marrow Transplant Group, Princess Margaret Hospital, Toronto, Ontario, Canada), Carlo Dufour, MD (EBMT Working Party Severe Aplastic Anemia, Gaslini Children’s Hospital, Genova, Italy), and Marcelo C. Pasquini, MD (Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee).

Previous Presentations: Data from this study were presented at the 41st Annual Meeting of the European Society for Blood and Marrow Transplantation; March 25, 2015; Istanbul, Turkey.

Additional Contributions: We thank all 23 WBMT member societies (http://www.wbmt.org/en/member-societies-of-wbmt/) and all transplant centers worldwide who contributed to the survey.

References
1.
Sureda  A, Bader  P, Cesaro  S,  et al.  Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50(8):1037-1056.
PubMedArticle
2.
Gratwohl  A, Baldomero  H, Gratwohl  M,  et al; Worldwide Network of Blood and Marrow Transplantation (WBMT).  Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study. Haematologica. 2013;98(8):1282-1290.
PubMedArticle
3.
Eapen  M, Le Rademacher  J, Antin  JH,  et al.  Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood. 2011;118(9):2618-2621.
PubMedArticle
4.
Scheinberg  P, Young  NS.  How I treat acquired aplastic anemia. Blood. 2012;120(6):1185-1196.
PubMedArticle
5.
Gratwohl  A, Baldomero  H, Aljurf  M,  et al; Worldwide Network of Blood and Marrow Transplantation.  Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303(16):1617-1624.
PubMedArticle
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