Different Sources of Hematopoietic Stem Cell Transplantation in Patients with Thalassemia Major: Relationship between Immune Reconstitution, Graft-Versus-Host Disease, and Viral Infections

Objective: To compare the relationship among immune reconstitution, graft-versus-host disease (GVHD), and viral infections in three kinds of hematopoietic stem cell transplantation(HSCT) using different host sources for thalassemia major(TM) patients: matched unrelated donor (MUD) HSCT, haploidentical (Haplo) HSCT with post-transplant cyclophosphamide (PTCy)-based prophylactic therapy, and TCRαβ-T cell-depleted HSCT (TDH).

Methods: A total of 191 TM patients in our center between October 2018 and June 2022 were included in this study, comprising three transplant groups: MUD group (n=56), PTCy group (n=45), and TDH group (n=90). Four-color flow cytometry was used to detect the proportions and absolute counts of lymphocyte subsets at the 12th month after transplantation for the three different donor types. The immune reconstitution was analyzed and compared with the occurrence of GVHD and virus infections.

Results:

1. Immune Reconstitution: (1) The ratio of helper cells (CD3 ⁺CD4 ⁺)/cytotoxic T cells (CD3 ⁺CD8 ⁺) at the 12 months after transplantation was compared among the three groups. There were statistically significant differences between the TDH and PTCy groups, as well as between the TDH and MUD groups(P=022 and 0.011, respectively). No statistical difference was found between the PTCy and MUD groups (P=0.932). The CD4 ⁺/CD8 ⁺ ratio in the TDH group recovered the fastest and had already returned to the normal reference range (0.7-2.7). (2) The comparison of B cells (CD3 ^-CD19 ⁺) at the 12 months after transplantation showed statistically significant differences between the TDH and PTCy groups, as well as between the MUD and PTCy groups (P=0.049 and 0.034, respectively). No statistical difference was found between the TDH and MUD groups (P=0.447). The recovery of B cells was faster in the TDH and MUD groups, while it was slowest in the PTCy group. (3) The comparison of natural killer cells (NK cells) (CD3 ^-CD56 ⁺) at the 12 months after transplantation showed statistically significant differences between the TDH and PTCy groups, as well as between the TDH and MUD groups (P=0.048 and 0.000, respectively). No statistical difference was found between the PTCy and MUD groups (P=0.366). The TDH group exhibited the fastest recovery of NK cells.

2. Chronic GVHD (cGVHD): (1) 7/90 cases (7.78%) of cGVHD appeared in the TDH group, 19/45 cases (42.22%) in the PTCy group, and 2/56 cases (3.57%) n the MUD group. (2) No statistical difference showed in the incidence of cGVHD between the TDH and MUD groups (P=0.500). There was a statistical difference in the incidence of cGVHD between the TDH and PTCy groups (P=0.000), as well as between the MUD and PTCy groups (P=0.000).

3. Viral Infection: (1) 22/90 cases (24.44%) of viral infection occurred in the TDH group, 7/45 cases (15.56%) in the PTCy group, and 6/56 cases (10.71%) in the MUD group. (2) Among the 90 cases of TDH group, the CD4/CD8 ratio at the 6 months after transplantation was 0.41±0.24 in the 22 cases with viral infection and 0.69±0.40 in the 68 cases without that. There was a statistical difference in the mean CD4/CD8 ratio between the two divisions in the TDH group (P=0.013).

Conclusion:The TDH group exhibited faster immune reconstitution compared to the other two groups, especially in terms of CD4/CD8 ratio, B cells, and NK cells. This may be related to two special factors for patients underwent TDH in our center: a rather high average infusion of CD34 cells (30×10 ⁶/kg) , and the preservation of γδ cells, B cells, and NK cells with the removing of TCRαβ-T cells in the TDH treatment protocol. The TDH and MUD groups showed a lower incidence of cGVHD, while the PTCy group had a higher incidence. The occurrence of viral infection in the TDH group was 24.44%. Also, the lower a CD4/CD8 ratio at the 6 months after transplantation, the higher the incidence of viral infection.

Table 1. The Absolute Counts of Lymphocyte Subsets at the 12th Month after Transplantation