Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients.
To evaluate the long-term immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), we prospectively screened standard immune parameters in a series of 105 patients, at a median time of 15 months after SCT. Analysing lymphoid phenotypes, in vitro immune functions and immunoglobulin levels, we found that, more than 1 year post SCT, cellular and humoral immunity was still altered in a significant number of patients. CD4+ T cells were < 200/microl in one third of patients, and the CD4/CD8 ratio was still reversed in 78% of patients. Almost all patients showed positive T-cell responses against mitogens, but antigen-specific proliferation assays identified 20% to 80% of non-responders. B-cell counts were reconstituted in 61% of the patients, but levels of total immunoglobulins were still low in 59%. In multivariate analyses, human leucocyte antigen (HLA) disparity between donor and recipient and chronic graft-versus-host disease were the leading causes affecting immune reconstitution. Interestingly, cytomegalovirus (CMV) infections were strongly associated with normal CD8+ T-cell counts. Studying the impact of impaired immune reconstitution on the rate of infections occurring in the 6 years following screening, we identified three parameters (low B-cell count, inverted CD4/CD8 ratio, and negative response to tetanus toxin) as significant risk factors for developing such late infections.
Maury
S
S
Department of Haematology-Bone Marrow Transplant, Hôpital Saint Louis, Paris, France.
Mary
J Y
JY
Rabian
C
C
Schwarzinger
M
M
Toubert
A
A
Scieux
C
C
Carmagnat
M
M
Esperou
H
H
Ribaud
P
P
Devergie
A
A
Guardiola
P
P
Vexiau
P
P
Charron
D
D
Gluckman
E
E
Socié
G
G
D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000276:immunology* / Q000628:therapy*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors; D013744:Tetanus Toxin / Q000008:administration & dosage; D014184:Transplantation, Homologous
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D013744:Tetanus Toxin; D016572:Cyclosporine; D001379:Azathioprine