Hematopoietic Cell Sources Tailored to the Patient
Physicians can select from three hematopoietic cell sources for their transplant patients — bone marrow, peripheral blood stem cells (PBSC) and umbilical cord blood. Although comparable outcomes have been achieved with all three sources, selection of the hematopoietic cells is based on several patient factors.
Marrow
Bone marrow has been a standard source of hematopoietic cells for more than 35 years. Transplant physicians may select marrow because:
Extensive clinical data are available about marrow transplant outcomes
Extensive information is available about the marrow donation experience
PBSC
For allogeneic transplants, PBSC is now used more often than marrow for adult patients (Figure 1). Some transplant physicians prefer PBSC for patients with advanced disease, and consider PBSC and marrow comparable for patients with early phase disease. [1] However, due to poorer outcomes in children, PBSC may not be the preferred graft source in pediatric transplants. [2] Physicians may select PBSC based on:
Faster neutrophil and platelet recovery [3]
Faster immune reconstitution [1,3]
Autologous transplants rely almost exclusively on PBSC rather than marrow (Figure 2), due to:
Umbilical cord blood transplants are used more often for pediatric patients, but cord blood use is growing in both adult and pediatric populations (Figure 1). Physicians may consider umbilical cord blood a good choice particularly for patients who need an unrelated donor and have an uncommon HLA type or are in urgent need of a transplant. Transplant physicians may select cord blood because:
HLA mismatch is better tolerated [4-7]
Cord blood is available more quickly than marrow or PBSC unrelated donors [6]
Reduced incidence and severity of acute GVHD [4-7]
Choosing a hematopoietic cell source for allogeneic transplant
A transplant physician chooses among the three sources of hematopoietic cells for a patient based on:
Published outcomes data
Availability of an appropriately matched, suitable donor (related or unrelated) or cord blood unit
Patient's disease, status and age
The level of urgency of the patient's need for transplant
When considering cord blood, the total nucleated cell count of matching cord blood units in relation to the patient's weight
Marrow, PBSC and umbilical cord blood cells differ in the match requirements, cell dose, time to donor availability, time to engraftment, risk of acute and chronic GVHD, and availability of cells, as shown in Table 1.
Hematopoietic Cell Sources for Allogeneic Transplant
Characteristic
Marrow
PBSC
Umbilical cord blood
HLA matching requirements
Close matching is a key factor influencing outcomes. For unrelated donor transplants, NMDP requires a minimum 5 of 6 HLA match.
Close matching is a key factor influencing outcomes. For unrelated donor transplants, NMDP requires a minimum 5 of 6 HLA match.
More permissive matching than marrow or PBSC. For unrelated donor transplants, NMDP requires a minimum 4 of 6 HLA match.
Time to neutrophil engraftment
Generally slower than PBSC, but faster than cord blood.
Generally faster than marrow and cord blood. [1,3]
Generally slower than marrow or PBSC.
CD34+ cell dose
A sufficient cell dose can be collected in all but rare instances.
Allows collection of a higher number of cells than marrow.
Cell dose is limited by size of the cord blood unit; some units may have an insufficient cell dose for larger patients. [8]
Time to identify and collect cells from unrelated donors
Average search time is 2 months.
Same as marrow.
Often available within 1 month.
Risk of acute GVHD in recipient
Risk is lower than PBSC. [9]
Risk is higher than marrow. [9]
Associated with reduced risk of acute GVHD. [4,5,6,10]
Risk of chronic GVHD in recipient
Risk is lower than PBSC.
Associated with more chronic GVHD and/or chronic GVHD that is more difficult to treat. [1,3,12,13]
Less risk than PBSC and marrow. [11]
Second donation (to salvage graft failure or relapse)
Potentially available, depending on donor availability.
Potentially available, depending on donor availability.
Not available; however a second unit may be quickly available.
Table 1. Characteristics of hematopoietic cell sources.
Studies continue on PBSC and cord blood
Both PBSC and cord blood are being studied under FDA investigational new drug (IND) protocols. Studies continue to investigate rates of GVHD and other characteristics of both cell sources. In addition:
The National Marrow Donor Program (NMDP) and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) are currently conducting a large, phase III clinical trial to determine whether there are differences in patient outcomes and/or donor experiences between marrow and PBSC unrelated donor transplants. [14]
Ways to overcome the limited cell dose of cord blood to enable transplants for larger adults are currently being studied. Methods under study include combining two or more closely matched cord blood units, the co-infusion of mesenchymal cells or PBSC, and ex vivo expansion of the cells. [4,6,8]
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
Wagner JE, Barker JN, DeFor TE, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood. 2002; 100(5):1611-1618. http://www.bloodjournal.org/cgi/content/full/100/5/1611
Barker JN, Weisdorf DJ, DeFor TE, et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood. 2005; 105(3):1343-1347. http://www.bloodjournal.org/cgi/content/full/105/3/1343
Kamani N, Spellman S, Hurley CK, et al. State of the art review: HLA matching and outcome of unrelated donor umbilical cord blood transplants. Biol Blood Marrow Transplant. 2008; 14(1):1-6. http://www.bbmt.org/article/PIIS1083879107005721/fulltext
Eapen M, Logan BR, Confer DL, et al. Peripheral blood grafts from unrelated donors are associated with increased acute and chronic graft-versus-host disease without improved survival. Biol Blood Marrow Transplant. 2007; 13(12):1461-1468. http://www.bbmt.org/article/PIIS1083879107003850/abstract
Laughlin MJ, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med. 2004; 351(22):2265-2275. http://content.nejm.org/cgi/content/abstract/351/22/2265
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
Flowers MED, Parker PM, Johnston LJ, et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood. 2002; 100(2):415-419. http://www.bloodjournal.org/cgi/content/full/100/2/415
Remberger M, Beelen DW, Fauser A, et al. Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors. Blood. 2005; 105(2):548-551. http://www.bloodjournal.org/cgi/content/full/105/2/548
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