Blood, 15 December 2001, Vol. 98, No. 13, pp. 3503-3503
Long-term immune reconstitution after marrow transplantation
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
-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.
Gérard Socié
Hospital Saint Louis; University Paris VII, France
