The Impact of CD34+ cell dose and T lymphocyte subsets on the incidence of acute and chronic graft-versus-host disease (GVHD)‎ following allogeneic peripheral blood stem cell transplantation

Abstract EN

Graft-versus-host disease continues to be a problem in allogeneic hematopoietic stem cell transplantatiorirThe skin, intestinal tract and liver are the 3 major target organs of GVHD.

The damage inflicted to these organs, the epithelial and endothelial cells in particular, by the conditioning regimens causes a release of various cytokines and a penetration of endotoxin into the systemic circulation.

Objectives: To study the impact of CD34* cell count on the incidence of acute and chronic GVHD in allogeneic peripheral blood stem cell transplantation (PBSCT), and to identify the impact of CD3*, CD4f and CD8" cell count on the incidence of acute GVHD.

Patients and Methods: A prospective study of 50 patients of different haematological disorders allografted with peripheral blood stem cells from HLA matched siblings (Group I) and 100 recipients of allogeneic PBSC transplantation were reviewed retrospectively (Group II) in the BMT center of Nasser Institute for Research and Treatment in Cairo.

Patients were classified into two subgroups, subgroup A patients who did not develop GVHD, while subgroup B were those who developed GVHD either acute or chronic.

Acute GVHD was graded according to Settle criteria (1995).

Patients were followed up to two years.

Results: 'The incidence of acute GVHD was similar (48% in Group I and 49% in Group II).

•Nine of the patients were of grade I to 11 andfifteen showed manifestations ofgrade 111 to IV acute GVHD.

•Skin GVHD occurred in approximately 57%, hepatic GVHD in 50% and GIT GVHD occurred also in 50%.

•The older the age of the patients, the higher the incidence of acute GVHD (P<0.01).

•Patients who received higher numbers of CD3/cells showed a higher incidence of acute GVHD (P<0.001).

Patients who developed acute GVHD grade III-VI received higher numbers of CDi4 cells than those who developed grades 1-11 (P<0.01) •Patients who developed gastrointestinal GVHD received higher number of CD3/ cells than those who developed hepatic or skin GVHD (P<0.01).

•In patients of subgroup B, CD{ x 106/ Kg was higher than patients in subgroup A but the difference was statistically insignificant.

The same was noted after grading of acute GVHD, as patients who developed acute GVHD grade I-II were infused with lower numbers of CD3* cells than those who developed GVHD grade III-IV, but the difference was statistically insignificant.

•The infused CD4* and CDs cells were significantly higher (P<0.001) in subgroup B compared to subgroup A.

The increased number of infused CD4+ and CD8+ cells was statistitdlly significant in patients who developed grade III-VIGVHD (P<0.01) than in those who developed GVHD grade l-ll.

'On the other hand patients who developed chronic GVHD were infused with lower numbers (P<0.01) of CD34* cell than those who did not develop chronic GVHD.

Conclusion: Acute and chronic GVHD remains an important factor affecting morbidity and mortality after allogeneic PBSCT.

The higher the number of infused CD34 * cells, CD4+ cells, CD8* cells, the severer the form of acute GVHD.

Patients who developed gastrointestinal GVHD received higher numbers of these cells than those who developed skin or hepatic GVHD.

While patients who developed chronic GVHD either de-novo or on top of acute GVHD received lower numbers of infused CD34+ cells.