ASH Conference Follow-up

NMDP Convenes Hematology Experts at December Meeting

At the invitation of the National Marrow Donor Program^® (NMDP), six of the world's leading experts on stem cell transplantation gathered at a symposium during the annual meeting of the American Society of Hematology. The symposium, titled "Advances in Transplantation of Hematopoietic Stem Cells from Unrelated Volunteer Donors," took place on December 7 in Orlando, Fla.

The topics discussed at the symposium ranged from basic research on stem cell transplantation to the latest developments in treating several blood and marrow diseases.

The speakers discussed:

• Using data from the NMDP Registry for research
• The importance of using HLA-matched donors and patients
• Using peripheral blood stem cells (PBSC) in transplantation
• Using unrelated donor stem cell transplantation to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia

Alexandra Filipovich, M.D., from the Children's Hospital Medical Center in Cincinnati, Ohio, spoke on how research using data collected by the NMDP has improved survival among stem cell transplant recipients. Several ongoing studies sponsored by the NMDP have used highly accurate molecular-based (DNA) tissue typing methods to re-examine the degree of HLA matching in approximately 2,000 NMDP transplants.

One outcome of these studies, which used blood samples collected from NMDP donors and recipients, was that HLA mismatching is better tolerated by younger patients. Another NMDP study examined the practice of removing T-cells from marrow grafts in an effort to reduce graft-versus-host disease (GVHD). While this did have the desired effect on GVHD, the study found that patients receiving T-cell-depleted grafts had a lower five-year survival than recipients of non-depleted marrow grafts.

Transplant physicians searching for donors for their patients always seek a perfect HLA match. But when an HLA-matched donor is not available, these physicians must then consider selecting a slightly mismatched donor. Neal Flomenberg, M.D., of the Thomas Jefferson University in Philadelphia, Penn., presented data on the impact of HLA mis-matching on survival after unrelated donor bone marrow transplantation. Dr. Flomenberg and his colleagues studied 1,874 transplants coordinated by the NMDP from 1988-1996. The results indicated that a single mismatch at the HLA-A, -B, or -C locus led to higher incidences of grades III-IV acute GVHD and increased mortality. A mismatch at the class II HLA-DR locus also led to higher rates of acute GVHD and mortality, but mismatches at the HLA-DQ had no effect on either outcome.

Dennis Confer, M.D., chief medical officer of the NMDP, discussed the NMDP's peripheral blood stem cell (PBSC) program. The NMDP coordinated its first primary PBSC transplant in July 1999, and Dr. Confer reported that the program has been expanding rapidly ever since. The NMDP expects that approximately 40% of the NMDP's transplants in 2002 will be PBSC transplants. Dr. Confer presented preliminary results comparing PBSC transplants to marrow transplants, including:

• Superior platelet engraftment in PBSC transplants
• No difference in rates of chronic GVHD
• No difference in rates of relapse-free survival

Philip Bierman, M.D., of the University of Nebraska, presented results of an examination of 262 non-Hodgkin's lymphoma (NHL) patients who received bone marrow transplants coordinated by the NMDP from 1990-2000. The median follow-up of surviving patients was 2.0 years, and the estimated five-year survival of these NHL patients was 24%. The patients with low-grade NHL had significantly better survival than those with other types of the disease, and the best five-year failure-free survival rate was achieved by chemotherapy-sensitive first-relapse patients. Among the factors that lowered transplant success were older patient age, advanced disease at time of transplant, and poor performance status.

Steven Pavletic, of the University of Nebraska Medical Center, discussed results from a study of 38 patients with B-cell chronic lymphocytic leukemia (CLL) who were transplanted between 1993 and 1999 using marrow procured by the NMDP. The study revealed that the 3-year disease-free survival rate was 45%. Younger age was significantly associated with better overall survival. Because younger CLL patients typically have a more rapidly progressing form of the disease, Dr. Pavletic stated that these patients should be considered strong candidates for transplantation.

Jan Cornelissen, M.D., of the Daniel den Hoed Cancer Center in Rotterdam, The Netherlands, spoke on using unrelated donor marrow transplantation to treat poor-risk patients with acute lymphoblastic leukemia (ALL). Dr. Cornelissen and his colleagues studied 127 poor-risk ALL patients transplanted between 1988 and 1999 using marrow obtained by the NMDP. Poor risk was defined as the presence of gene translocations in any of three locations.

Although there was a high rate (54%) of transplant-related mortality in patients who were in their first complete remission (CR1) at the time of transplant, these patients had the best overall survival. CR1 patients had a 40% overall survival at 2 years of follow-up, compared to 17% survival for patients in second or third complete remission, and 5% survival for patients in relapse or with induction failure. The researchers also found that T-cell depletion of the marrow graft prior to infusion had no significant effect on survival.