With an increasing number of patients and improved results after allogeneic hematopoietic stem cell transplantation, studies on long-term outcomes are of major importance in the 2000s. Patients who are alive and disease-free 2 years after transplantation generally have an excellent prognosis, and over 80% can be considered cured from their original disease. But late death and late complications may affect these long-term survivors. Among these late complications, infections (mainly bacterial and viral) are the leading cause of late mortality and morbidity. The main risk factor for developing late infection after transplantation is chronic graft-versus-host disease and its treatment with steroids. Our knowledge of the immune status of long-term survivors is, however, still scant. It is generally assumed that infection and biologic parameters such as T-cell subsets and γ-globulin levels return to normal levels within 5 years after transplantation.
Storek and colleagues (page 3505) report on the immune status of 72 patients surviving 20-30 years after marrow grafting. In this unique patient cohort, the rate of clinically significant infection was low (one every 14 years). The authors were also able to study leukocyte subsets, IgG2, and antigen-specific IgG levels in 33 of the 72 patients and in 16 of their original donors. Main leukocyte subsets (monocytes, NK cells, B cells, and CD4 and CD8 T cells) were found to reach the same levels in patients as in both their donors and age-matched controls. The only fine abnormality the authors found was a long-lasting defect in thymopoiesis in older patients. Using T-cell receptor excision circles (TRECs) as a marker of de novo–generated CD4 cells, Storek et al found that the count of TREC+ CD4 T cells in the patients was lower than in their donors if the patients were over the age of 18 years. The authors conclude that, overall, the immunity of patients receiving transplants more than 20 years ago is near normal.
Without diminishing the outstanding interest of this study, I would like to underline its unavoidable flaw. Most of the patients (23 out of 33; 70%) who were studied biologically had aplastic anemia, most (19 patients) received cyclophosphamide only as conditioning regimen, and less than 20% had chronic graft-versus-host disease. Thus, other such studies (in leukemia after irradiation-based conditioning, for example) on the long-term recovery of the immune system following allogeneic marrow transplantation would be highly warranted.
