Most Patients in Need of HCT Can Now Get Transplants

Karen K. Ballen, MD
Published: Monday, Dec 11, 2017
VCUKaren K. Ballen, MD
Karen K. Ballen, MD
 
Section Head, Hematologic Malignancies and Stem Cell Transplantation
Department of Medicine, Division of Hematology/Oncology
University of Virginia Cancer Center
Charlottesville, VA
Strategic Partnership
Hematopoietic cell transplant (HCT) is potentially curative for a wide variety of malignant diseases, including acute and chronic leukemias, lymphoma, and myelodysplasia. Historically, preferred donors for HCT have been human leukocyte antigen (HLA)-matched sibling donors (MSDs). Each full biologic sibling has a 25% chance of being HLA identical to the patient.

Given the average family size in the United States, only about 30% of US patients will have an MSD available. Most patients referred for HCT will require an alternative donor graft. These graft sources may include a matched unrelated donor via the Be The Match program, umbilical cord blood (UCB), or a partially matched family donor (haploidentical) transplant.

This review summarizes the chance of finding a donor and the pros and cons of each of these graft sources. The fantastic news is that due to great progress in alternative donor transplants, almost all transplant-eligible patients (up to age 75 years) in 2017 will be able to find a suitable donor and proceed to transplant, a major advance over the past 10 years.

Unrelated Donor Transplant

The National Marrow Donor Program (NMDP), located in Minneapolis, Minnesota, was founded in 1986 and has grown to more than 25 million volunteer donors worldwide.1 Now known as Be The Match, this organization is supported by government funds and philanthropy.

The chance of finding an adult volunteer matched unrelated donor (MUD) via the NMDP depends on the ethnicity of the recipient. White Caucasians of Northern European descent have the greatest chance of finding an MUD. Chances of finding an MUD are significantly less for African American or Hispanic recipients due to HLA polymorphisms and the composition of the registry.2

Overall survival and disease-free survival (DFS) are now similar in MSD and MUD recipients.3 More recently, the use of mismatched unrelated transplant, defined as high-resolution DNA matching at 7/8 of the HLA loci, has increased the availability of unrelated donors for minority patients. African- American patients have a 23% chance of finding an MUD in the registry but a 70% chance of finding an HLA-mismatched unrelated donor (MMUD), and better HLA matching has improved outcomes over the last 10 years.4 Novel techniques, such as the use of bortezomib, have decreased graft-versus- host disease (GVHD) after MMUD transplants.5

Umbilical Cord Blood

UCB can be harvested from the umbilical cord after the delivery of the baby or from the placenta after the delivery of the placenta. There is no known risk to the mother or the baby. UCB contains blood that forms progenitor cells similar to bone marrow or peripheral blood stem cells.6

Currently, UCB transplants (UCBTs) in adult recipients account for approximately 10% of the alternative donor transplants performed in the United States.7 UCB units are readily available, have decreased rates of chronic GVHD compared with other graft sources, and require less strict HLA matching than units from MUD (Table).8 UCBT has been associated with a decreased rate of relapse, especially in patients with minimal residual disease.9

 

Table. Comparison of HCT Graft Sources

Table. Comparison of HCT Graft Sources
GVHD indicates graft-versus-host disease; HCT, hematopoietic cell transplant; UCBT, umbilical cord blood transplant. Ballen KK, Koreth J, Chen YB, Dey BR, Spitzer TR. Blood. 2012;119(9):1972-1980. doi: 10.1182/blood-2011-11-354563.
 
Disadvantages of UCBT include an increased risk of infections, particularly viral infections, which can lead to early transplant-related mortality.10 The cost of each UCB unit is approximately $40,000; many UCBTs in the United States are performed with double UCBTs, at a cost of $80,000 for graft acquisition alone. Several studies have demonstrated comparable survival among UCBT and other graft sources.11,12 UCBT is a reasonable transplant alternative and should be considered when an MSD or MUD donor is not available.

Haploidentical Donor

Haploidentical (haplo) donors are half-matched donors. A parent or a child and 50% of siblings will be a half match to the patient. Advantages of haplo donors are their ready availability, less strict HLA matching, and decreased cost of graft acquisition (Table).


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