Trends in Allogeneic Transplants
Approximately 20,000 allogeneic hematopoietic cell transplants (bone marrow, PBSC, or cord blood transplants — BMT) are performed annually worldwide, and approximately 4,300 patients are transplanted annually using unrelated donors or cord blood units through the National Marrow Donor Program (NMDP) and its Be The Match RegistrySM.
Since 1986, when the NMDP was founded, the NMDP has facilitated more than 33,000 marrow, peripheral blood stem cell (PBSC), and cord blood transplants. Recent growth in the number of NMDP transplants has been especially dramatic, with more than 4,300 transplants in 2008 alone, compared with 3,600 in 2007. This represents a 17% increase.
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Improved survival with unrelated transplantation
A major reason for the continued increase in unrelated donor transplantation is the steady improvement in transplant outcomes. This is in turn due to several clinical advances such as more precise HLA typing and advances in patient care. Table 1 shows that NMDP transplant outcomes have improved nearly 10% in just four years.| Improved Survival with Unrelated Transplantation | ||
| Report Year | Period | One-Year Survival |
| 2003 | 1996-2001 | 42.2% |
| 2006 | 2000-2004 | 48.8% |
| 2007 | 2001-2005 | 51.5% |
Recent studies have demonstrated that unrelated donor transplant outcomes are now comparable to related donor transplant outcomes in several patient populations. [1-5]
In addition, analyses of NMDP transplants from 1987-2006 have shown that survival has consistently, and sometimes dramatically, improved over time in each major disease category. These analyses were published in the September 2008 supplement to Biology of Blood and Marrow Transplantation to mark the NMDP's 20th anniversary. (See Saving Lives through Blood and Marrow Transplantation: 20 years of the NMDP.)
Trends in diseases treated
Several other trends in allogeneic transplantation have emerged during the last decade:- An increase in transplants for AML, ALL, MDS, and lymphomas (Fig. 1)
- A decline in transplants for CML (Fig. 1)
- An increase in transplants for non-malignant diseases (Fig. 2)
- Increased use of cord blood and PBSC grafts (Figs. 3-5)
- Increased use of transplants for patients >50 years (Figs. 6-7)
As shown in Figure 1, the most dramatic growth in allogeneic transplantation has been in patients with AML. Since AML is mainly a disease of older adults, a major reason for this growth is the use of non-myeloablative or reduced-intensity transplants that have expanded transplant therapy to older patients who would otherwise be excluded from this therapy.
Figure 1.
NMDP Transplants by Patient Diagnosis, Malignant Diseases 1998-2008. (NMDP data) (NMDP data is fiscal year data through September 30, 2008)
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Figure 1 shows that the number of transplants for AML, ALL, MDS, and lymphoma have also increased significantly. The advent of reduced-intensity or non-myeloablative transplants is also a prime reason for this increase. In addition, improved HLA matching, advances in conditioning regimens, advances in post-transplant supportive care -- including improved management of GVHD, CMV disease, and infections -- have also contributed to the growing number of allogeneic transplants in general.
Figure 2.
NMDP Transplants by Patient Diagnosis, Non-Malignant Diseases 1998-2008. (NMDP data)
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Figure 2 shows that NMDP transplants for non-malignant diseases has grown for most diseases, with the most rapid growth being seen in severe aplastic anemia (SAA). This follows the trend seen in the related-donor setting, where allogeneic transplantation is the preferred first-line treatment for SAA patients <40 years old who have a matched related donor. [6]
Survival of unrelated donor transplantation in patients with SAA is now approaching 60%. [7] Use of unrelated donor transplantation in SAA may continue to grow following the 2007 publication of a study showing that allogeneic transplantation is better than immunosuppressive therapy as second-line treatment in pediatric SAA. [8]
The increase in allogeneic transplantation for many other non-malignant diseases can also be attributed to improved HLA matching, advances in conditioning regimens and advances in post-transplant supportive care.
Increased use of cord blood and PBSC grafts
Figure 3 shows the growing use of PBSC and cord blood as graft sources in allogeneic transplantation. In 2008, 74% of adult donors – more than 2,500 – donated PBSC to patients through the NMDP. In 2008, 898 cord blood transplants were facilitated by the NMDP, which represented 21% of the total number of NMDP transplants in 2007. This is a 39% increase from 2007, when the NMDP facilitated 648 cord blood transplants.
Figure 3.
NMDP Transplants by Cell Source (bone marrow, peripheral blood stem cells or cord blood), 1988-2008. (NMDP data)
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Figures 4 and 5 show that cord blood is used more often in pediatric patients than in adult patients. However, recent studies have demonstrated that this stem cell source can be successfully used in adults and so its use is growing in this patient population. [9-11]
Figure 4.
NMDP Transplants in Adults by Cell Source (bone marrow, peripheral blood stem cells or cord blood), 1988-2008. (NMDP data)
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Figure 5.
NMDP Transplants in Pediatric Patients by Cell Source (bone marrow, peripheral blood stem cells or cord blood), 1988-2008. (NMDP data)
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A comparison of Figures 4 and 5 shows that PBSC is used less frequently in pediatric patients undergoing allogeneic transplantation than in adult patients, which is due to poorer outcomes in children receiving PBSC transplants. [12]
Increased use of transplants for patients >50 years
Figure 6 shows the increased number of older patients (>50 years) who have received unrelated donor transplants through the NMDP. In 2008, 36% of NMDP transplants, representing more than 1,500 transplants, were for patients aged 50 and older. Figure 7 shows the same data, but using smaller age groups, including separating the >50 patients into two groups: 51-64 and >64 years. In 2008, 303 patients who were older than 64 received transplants through the NMDP.This increase is due in large part to the increased use of non-myeloablative or reduced-intensity transplants that have expanded transplant therapy to older patients who would otherwise be excluded from this therapy.
Figure 6.
NMDP Transplants by Patient Age and Year, 1997-2008. (NMDP data)
Figure 7.
NMDP Transplants by Year and Patient Age, 1998-2008. (NMDP data)
To read about other trends in the use of hematopoietic cell transplantation, see Changing Trends in Diseases and Patients Treated.
References
- Eapen M, Rubinstein P, Zhang MJ, et al. Comparable long-term survival after unrelated and HLA-matched sibling donor hematopoietic stem cell transplantations for acute leukemia in children younger than 18 months. J Clin Oncol. 2006; 24(1):145-151.
http://www.jco.org/cgi/content/abstract/24/1/145 - Kiehl MG, Kraut L, Schwerdtfeger R, et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol. 2004; 22(14):2816-2825.
http://www.jco.org/cgi/content/abstract/22/14/2816 - Kennedy-Nasser AA, Leung KS, Mahajan A, et al. Comparable outcomes of matched-related and alternative donor stem cell transplantation for pediatric severe aplastic anemia. Biol Blood Marrow Transplant. 2006; 12(12):1277-1284.
http://www.bbmt.org/article/PIIS1083879106004976/abstract - Moore J, Nivison-Smith I, Goh K, et al. Equivalent Survival for Sibling and Unrelated Donor Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia. Biol Blood Marrow Transplant. 2007; 13(5):601-607.
http://www.bbmt.org/article/PIIS1083879107001188/abstract - Kennedy-Nasser AA, Bollard CM, Myers GD, et al. Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. Biol Blood Marrow Transplant. 2008; 14(11): 1245-1252.
http://dx.doi.org/10.1016/j.bbmt.2008.08.010 - Bacigalupo A, Brand R, Oneto R, et al. Treatment of acquired severe aplastic anemia: Bone marrow transplantation compared with immunosuppressive therapy—the European Group for Blood and Marrow Transplantation experience. Semin Hematol. 2000; 37(1):69-80.
http://www.seminhematol.org/article/PIIS0037196300900313/abstract - Viollier R, Socié G, Tichelli A, et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplant. 2007; 41(1):45-50.
http://dx.doi.org/10.1038/sj.bmt.1705894 - Kosaka Y, Yagasaki H, Sano K, et al. Prospective multicenter trial comparing repeated immunosuppressive therapy with stem cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia. Blood. 2007; 111(3):1054-1059.
http://dx.doi.org/10.1182/blood-2007-08-099168 - Takahashi S, Ooi J, Tomonari A, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood. 2007; 109(3):1322-1330.
http://bloodjournal.hematologylibrary.org/cgi/content/abstract
/109/3/1322 - Schoemans H, Theunissen K, Maertens J, et al. Adult umbilical cord blood transplantation: a comprehensive review. Bone Marrow Transplant. 2006; 38(2):83-93.
http://www.nature.com/bmt/journal/v38/n2/full/1705403a.html - Brunstein CG, Barker JN, Weisdorf DJ et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood. 2007; 110(8):3064-3070.
http://bloodjournal.hematologylibrary.org/cgi/content/abstract
/110/8/3064 - Eapen M, Horowitz MM, Klein JP, et al. Higher mortality after allogeneic peripheral-blood transplantation compared with bone marrow in children and adolescents: The Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry. J Clin Oncol. 2004; 22(24):4872-4880.
http://www.jco.org/cgi/content/abstract/22/24/4872
