Late Mortality After Autologous Transplantation

Abstract & Commentary

By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago

Dr. Artz reports no financial relationships with this field of study.

Synopsis: Survivors 2 years or more after autologous stem cell transplant for AML, ALL, NHL, and HD remain at significant risk of death, with 29% mortality, almost entirely between 2 and 10 years after transplant. While 56% died of relapse of the primary disease, 43% died from treatment related complications, many of whom suffered from therapy related MDS or AML. This study suggests these patients must be followed closely for an extended period of time.

Source: Bhatia S, et al. Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Blood. 2005; 105:4215-4221.

Autologous hematopoietic-cell transplantation has become increasingly employed, primarily as therapy for high-risk and relapsed hematologic malignancies such as multiple myeloma, lymphoma, and acute leukemia. Even though more than 50% of stem cell transplant procedures use autologous, rather than allogeneic (ie, donor) cells, the literature on long-term follow-up has only detailed survivors after allogeneic transplants. This report details late mortality after autologous transplantation.

Bhatia and colleagues present data from the Bone Marrow Transplant Survivors Study (BMTSS), where long-term outcomes of individuals who have survived more than 2 years after transplant are ascertained as well as age and sex-matched siblings. Data on deaths was obtained from the Social Security Death Registry, National Death Index, and medical records. Death was categorized as related to disease relapse, treatment related complications, or neither.

Among the 854 patients followed, the median age at transplant was 36.5 years and median follow-up was 7.6 years. The diagnoses included acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and Hodgkin disease (HD). Twenty-nine percent of the cohort died, most within 2-5 years after transplant. By 10 years, the mortality rate approached that of the general population. While 56% of late deaths were due to relapse of the primary disease, 43% were due to treatment related complications. Interestingly, peripheral blood stem cells as opposed to harvested bone marrow was associated with an increased risk of therapy related MDS/AML. Fifteen percent of the cohort reported difficulties with holding a job or attending school, which was significantly higher than matched controls.

COMMENTARY

This large, observational study on survival 2 years or more after autologous stem cell transplant for patients with AML, ALL, NHL and HD is of major interest to oncologists who often follow patients after autologous stem cell transplantation, even if the procedure was performed elsewhere. Clearly, long-term complications of allogeneic stem cell transplantation, such as graft-versus-host disease and/or functional limitations, have been noted.1,2

The finding that 29% died, mostly within 2-5 years after transplant is surprisingly high, especially since many of these patients consider themselves cured. While a majority died from relapse, the fact that 43% of late deaths were treatment-related complications, many from therapy-related MDS/AML, suggests that such patients may benefit from close follow-up by an oncologist and that signs and symptoms may necessitate a thorough evaluation. The finding of increased risk of therapy related MDS/AML in recipients of peripheral blood stem cells requires further investigation. One major limitation is that conditions for which the procedure may not be curative, were not included, such as multiple myeloma or solid tumors (germ cell tumors, breast cancer).

The largest question which arises, and is not answered, is how best to follow such patients in light of the significant late mortality risk.

References

1. Socie G, et al. Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. N Engl J Med. 1999; 341:14-21.

2. Wingard JR, et al. Health, functional status, and employment of adult survivors of bone marrow transplantation. Ann Intern Med. 1991;114(2):113-118.