Intact T-cell regenerative capacity in childhood acute lymphoblastic leukemia after remission induction therapy

Abstract

Background: Acute lymphoblastic leukemia (ALL) is a bone marrow disease. This may adversely affect the capacity of T cells to recover from chemotherapy-induced T-cell depletion and thus contribute to the prevailing immune deficiency in ALL patients.

Procedure: We tested the capacity of T-cells to regenerate in 18 ALL children in first clinical remission (median age 4.2 years) at the time of hematologic reconstitution after BFM-ALL induction therapy (treatment-free interval 22 days, median; range 12 to 52 days). All patients had experienced a period of leukopenia (white blood cell count [WBC] <0.95 x 10(9)/l, median) during the final four weeks of induction therapy. T-cells and T-cell subsets were examined by FACS.

Results: At the time of investigation the WBC was near normal (3.5 x 10(9)/l, median). Surprisingly, most cases (78%) showed a complete regeneration of T-cells and its subsets including 1) normal total (CD3+) T-cells (1635/microl, median; range 756-3440/microl); 2) normal T-helper (CD4+) cells (697/microl, median; range 128-1523/microl); and 3) normal T-cytotoxic/suppressor (CD8+) cells (686/microl, median; range 348-1540/microl). Eight patients achieved a normal CD4+/CD8+ ratio (0.8, median). Subset analyses of T-helper cells revealed a normal proportion of CD4+CD45RA+ cells (52%, median) in all but one patient below the age of 6 years, indicating an intact residual thymic activity. No correlation was observed between age at diagnosis and a normal CD4+ count (r = 0.086) or between a normal CD4+ count and a normal proportion of CD4+CD45RA+ cells r = 0.136). A long-term survey in four patients showed altered T-cells after reinduction and during maintenance therapy.

Conclusions: The findings suggest that ALL per se does not inhibit T-cell regenerative capacity. Thus, the frequently observed longlasting impairment of the T-cell system in ALL is attributable to the treatment rather than to the underlying disease.