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We read with interest the article by Nordøy et al1 dealing with the persistent changes in immune function 4–10 years after ABMT. The authors show that the early changes in the immune system observed after ABMT, in particular a reduction of CD4 and normalization of CD8 resulting in a decreased CD4/CD8 ratio, persist after a median of 5 years. On the basis of our experience we can confirm these findings also in the setting of autologous peripheral stem cell transplantation. Since 1996 we have studied 40 patients (25 male; 15 female) with a median age of 36 years (range 19–60 years) undergoing peripheral blood selected (CD34+) (nine patients) or unselected autologous stem cell transplantation (31 patients). Reasons for transplantation were: non-Hodgkin's lymphoma (26 patients), Hodgkin's lymphoma (14 patients) (patient characteristics are shown in Table 1). The purpose of the study was to investigate immunological reconstitution using a test panel (CD3, CD19, CD4, CD8, CD4/CD8, CD16/56, CD3HLADR). All patients entering the study were required to have had at least 12 months follow-up, and to be in continuous complete remission after PBPCT without any chemo-radiotherapy or biological response modifier. We performed annual follow-ups, studying 73 controls with a median of two controls per patient (range 1–3). We arbitrarily subdivided patients into three groups according to the time and number of controls per patient: group A, 35 patients with a median follow-up of 14 months (range 12–65 months); group B, 22 patients with a median follow-up of 28 months (range 24–82 months); and group C, 15 patients with a median follow-up of 55 months (range 36–96 months). We observed a persistent reduction in CD4 T lymphocytes with a trend for normalization without statistical differences between the three groups. CD8 assay showed values around the normal range in groups A and B with normalization in the third group. Recovery of CD4 and normalization of CD8 produced a trend for recovery of the CD4/CD8 ratio with statistical differences between groups A and C (Kruskal–Wallis post-hoc test P = 0.007). Total T lymphocytes were constantly in the normal range and total B lymphocytes were high with respect to normal values, in all groups. Effector cells including activated T lymphocytes (CD3-HLA-DR) and natural killer (CD16–56) were persistently above the normal range without statistical differences in the three groups (results are shown in Table 2).
As did Nordøy et al1 we confirmed a tendency towards higher CD4 counts between the three groups even if statistical significance was not reached. Concomitantly, CD8 cells progressively decreased to the normal range in group C. These data, confirmed by previous studies,234 show a trend to normalization of the CD4/CD8 ratio that is statistically significant with prolonged follow-up. In conclusion, we demonstrated that the normalization process of CD4 and CD8 cells continues even after many years so that restoration of immune function may be possible with extended follow-up after PBSCT.
Laurenti L, Sica S, Salutari P et al. Assessment of hematological and immunological function during long-term follow-up after peripheral blood stem cell transplantation Haematologica 1998 83: 138–142
Laurenti L, Sica S, Sorà F et al. Long term immune recovery after immunoselected CD34+ PBPCT and unselected PBPCT: a case-control study Haematologica 1999 84: 1100–1103
Laurenti, L., Sica, S., Sorà, F. et al. Persistent immunological changes 55 months after PBPCT. Is the restoration of immune function possible with a longer follow-up?.
Bone Marrow Transplant26, 707–708 (2000). https://doi.org/10.1038/sj.bmt.1702595