Cell Sources


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Cell Sources

Physicians can select from three hematopoietic cell sources for patients in need of transplantation—bone marrow, peripheral blood stem cells (PBSC), and umbilical cord blood. Physicians can often select the hematopoietic cells based on a patient's characteristics, disease, and disease status.

Currently, the most common graft choice of transplant physicians is peripheral blood stem cells, which are used in 83% of all transplants. Bone marrow and umbilical cord blood are used in 17% and 9% of transplants, respectively.

Clinical Factors

Many factors can enter into the clinical decision of selecting the hematopoietic cell source that is best for each patient. Several recent studies have shown that comparable allogeneic transplant outcomes are achieved regardless of hematopoietic cell graft used. [1,2,3,4] View outcomes by cell sources in related and unrelated donor transplantation, also showing comparable transplant outcomes, regardless of graft source.

Marrow

Bone marrow has been a standard source of hematopoietic cells for more than 40 years. Transplant physicians may select marrow because:

  • Chronic graft-versus-host disease (GVHD) is lower and less severe than in PBSC transplants [2]
  • For pediatric patients undergoing allogeneic transplant, survival rates are higher for marrow than PBSC [5]

PBSC

For allogeneic transplants, PBSC is used more often than marrow for adult patients. Physicians may select PBSC based on:

  • Faster neutrophil and platelet recovery [2]
  • Faster immune reconstitution [2]

Autologous transplants in both pediatric and adult patients rely almost exclusively on PBSC rather than bone marrow. Reasons include:

  • Easier collection of cells
  • More rapid hematopoietic recovery
  • Easier graft manipulation (e.g., CD34+ cell selection, tumor cell purging) [6]

Umbilical Cord Blood

Physicians may consider umbilical cord blood for patients who need an unrelated donor and have an uncommon HLA type (making it difficult to identify a full match), or are in urgent need of a transplant. Transplant physicians may select cord blood because:

  • HLA mismatch is better tolerated [7]
  • Cord blood is available more quickly than marrow or PBSC unrelated donors [7]
  • Reduced incidence and severity of acute GVHD [7,8]

Umbilical cord blood transplants are used more often for pediatric patients, but cord blood use has grown in both adult and pediatric populations. [9]

Study Results: Marrow vs. PBSC

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducted a large, phase III clinical trial to determine whether there were differences in patient outcomes and/or donor experiences between PBSC and marrow in unrelated donor transplants and incidence of GVHD. [2]

The study found that PBSC and bone marrow transplant recipients had comparable two-year survival: 51% vs. 46%, respectively (p=0.29). However, the incidence of chronic GVHD at two years was higher in patients who received PBSC compared with those who received marrow: 53% vs. 41%, respectively (p=0.01). Chronic GVHD was also more severe in recipients of PBSC grafts. The overall incidence of graft failure in the PBSC group was significantly lower compared to the incidence in the bone marrow group: 3% vs. 9%, respectively (p=0.002).

Use of Cord Blood in Different Patient Populations


Use of Cord Blood in Pediatric Transplantation

Figure 2 shows the use of umbilical cord blood transplants in pediatric patients. In 2015, cord blood units were used in approximately 33% of pediatric transplants facilitated by NMDP/Be The Match. In comparison, approximately 11% of adult transplant recipients received umbilical cord blood in 2015.

Figure 2. Transplants by Cell Source, Pediatric Patients, 1990-2016

Number of Unrelated Transplants, Pediatric Recipients, By Cell Source

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Use of Cord Blood for People of Color

Because HLA mismatch is better tolerated in cord blood transplantation, the use of this stem cell source has been particularly beneficial for people of color who have traditionally had more difficulty finding a suitably matched marrow or PBSC donor on volunteer donor registries.

In 2015, 29 percent of umbilical cord blood transplants were for transplant patients of color, while 12% of Caucasian transplant recipients received a cord blood unit. Figure 3 shows the use of cord blood units among five different ethnic groups.

Figure 3. Role of Cord Blood in Transplants by Ethnic Background

Role of Cord Blood in Transplants by Ethnic Background

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Use of Cord Blood in Adult Patients

Transplant physicians are developing ways to overcome the limited cell dose of an umbilical cord blood unit to permit more cord blood transplants in larger adults. Using two or more umbilical cord blood units to increase the cell volume is an option for some adult patients. [7] In 2017, 37% of cord blood transplants facilitated by NMDP/Be The Match used more than one umbilical cord blood unit.

Other methods being developed include the co-infusion of mesenchymal cells or PBSC, and ex vivo expansion of cord blood cells prior to infusion. [8]


References

  1. de Latour RP, Brunstein CG, Porcher R, et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant. 2013; 19(9): 1355-1360. Access
  2. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012; 367(16): 1487-1496. Access
  3. Nagler A, Labopin M, Shimoni A, et al. Mobilized peripheral blood stem cells compared with bone marrow as the stem cell source for unrelated donor allogeneic transplantation with reduced-intensity conditioning in patients with acute myeloid leukemia in complete remission: An analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012; 18(9): 1422-1429. Access
  4. Brunstein CG, Eapen M, Ahn KW, et al. Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes. Blood. 2012; 119(23): 5591-5598. Access
  5. 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. Access
  6. Ooi J. Cord blood transplantation in adults. Bone Marrow Transplant. 2009; 44(10): 661-666. Access
  7. Brunstein CG, Gutman JA, Weisdorf DJ, et al. Allogeneic hematopoietic cell transplantation for hematological malignancy: Relative risks and benefits of double umbilical cord blood. Blood. 2010; 116(22): 4693-4699. Access
  8. Rocha V, Broxmeyer HE. New approaches for improving engraftment after cord blood transplantation. Biol Blood Marrow Transplant. 2010; 16(1, Suppl.): S126-S132. Access
  9. Rafii H, Ruggeri A, Volt F, et al. Changing trends of unrelated umbilical cord blood transplantation for hematologic diseases in patients older than fifty years: A Eurocord-Center for International Blood and Marrow Transplant Research Survey. Biol Blood Marrow Transplant. 2016; 22(9): 1717-1720. Access