The MDS Beacon™

Umbilical cord blood transplantation with a mismatched donor produces similar outcomes as bone marrow transplantation with a mismatched donor, according to results from a recent analysis conducted in Japan.

Based on their findings, the researchers conclude that umbilical cord blood transplantation with a mismatched donor is an effective treatment alternative if a matched donor for a bone marrow transplant is not available.

Furthermore, if transplantation is needed within a short time frame, the researchers recommended that umbilical cord blood transplantation be used over a mismatched bone marrow transplantation since little time is needed for an umbilical cord blood transplantation.

Stem cell transplantation is currently the only potentially curative treatment available for patients with myelodysplastic syndromes (MDS). In this procedure, a patient’s stem cells are destroyed with chemo­therapy or radiation and then replaced with stem cells from a healthy donor.

In order to increase the chances of a successful transplant, physicians search for a matched donor by comparing the genetic sequences for the human leukocyte antigen (HLA) of the recipient and potential donors. HLA is a cellular surface protein that plays a major role in the immune system’s identification of foreign materials.

According to the study authors, only 30 percent of transplant-eligible patients have a matched donor. In cases where an HLA-matched donor is unavailable, physicians frequently select a donor with a single HLA mismatch for the transplantation.

There are four protein variations of HLA: HLA A, B, C, and DRB1. A recent study showed that mismatches at HLA C and DRB1 result in the worst transplant outcomes (see related Beacon news).

Umbilical cord blood transplantation is increasingly being considered as an alternative to bone marrow transplantation for patients who cannot find a matched donor.

In the current study, Japanese researchers retrospectively analyzed data from 1,028 patients in Japan who underwent bone marrow transplantation and 351 patients who underwent umbilical cord blood trans­plan­tation to compare outcomes between the two procedures.

Of all the patients included in the analysis, 200 had MDS. The bone marrow transplants covered by the analysis took place between 2000 and 2005, while the umbilical cord blood transplants took place between 1996 and 2005.

The median age for patients who received umbilical cord blood transplants was slightly higher than that for patients who received bone marrow transplants (37 years versus 34 years).

The three-year survival rate for patients who received an umbilical cord blood transplant was 47 percent. This was similar to the three-year survival rate for patients who received single HLA-mismatched bone marrow transplants: 41 percent for mismatches at HLA DRB1 and 47 percent for mismatches at HLA A, B, or C. The survival rate for patients who received bone marrow transplants from donors with two HLA mis­matches was the lowest (38 percent).

Patients who received umbilical cord blood transplants had the slowest recovery of white blood cells and platelets. This, according to the Japanese researchers, is a major limitation of the umbilical cord blood procedure.

The researchers noted that several strategies have been investigated to speed up white blood cell recovery after transplantation, including screening patients for anti-HLA antibodies prior to transplantation, trans­plantation with two umbilical cord blood units, and direct injection of umbilical cord blood units into the bone marrow.

A common complication of stem cell transplants is graft-versus-host disease, in which the donor stem cells recognize the recipient’s immune system as foreign and attack it.

The rate of moderate to severe acute graft-versus-host disease was lowest in patients who received umbilical cord blood transplants (9 percent). By comparison, the rate in bone marrow recipients was 19 percent for mismatches at HLA DRB1, 18 percent for mismatches at HLA A, B, or C, and 22 percent for two HLA mismatches.

The researchers point out that the rates of acute graft-versus-host disease rates for umbilical cord blood transplants could actually have been even lower if it were not for the differences in preventative medication given to these patients. The majority of patients receiving umbilical cord blood transplants received cyclo­sporine A (Sandimmune), whereas the majority of patients receiving bone marrow transplants were given short-term methotrexate and Prograf (tacrolimus), which has been associated with reduced rates of severe acute graft-versus-host disease.

The risk of transplant-related death was also lower in patients who received umbilical cord blood trans­plants. The researchers speculated that the lower rates of acute graft-versus-host disease in patients who received umbilical cord blood transplants may have contributed to the decreased risk of transplant-related death.

For more information, please refer to the article in Biology of Blood and Marrow Transplantation (abstract).