Allogeneic peripheral blood stem cell transplantation with CD34+-cell selection and delayed T-cell add-back in adults. Results of a single center pilot study.
OBJECTIVE
Allogeneic peripheral blood stem cell transplantation with CD34+ cell-selection (CD34+-PBSCT) allows rapid hematologic engraftment with a reduction in graft-versus-host disease (GVHD), although concerns exist regarding the increased risk of tumor relapse associated with T-cell depletion of the graft. Delayed T-cell add-back (TCAB) after such transplants may restore the graft-versus-tumor effect while achieving a reduced early transplant-related mortality due to less GVHD in a group of patients at high risk of early death (i.e., age >= 45 years).


METHODS
Ten patients 45 years of age or older with hematologic malignancies received a CD34+-PBSCT and cyclosporin A (CyA) to prevent acute GVHD, followed by a planned delayed donor TCAB of 107 T-cells/kg to restore the graft-versus-tumor effect. The infused graft included a median of 6.3x106 CD34+ cells/kg and 4.4x104 CD3+ cells/kg.


RESULTS
Engraftment was prompt in all cases. Four patients developed acute GVHD after the CD34+-PBSCT and/or chronic GVHD after CyA withdrawal and did not proceed to TCAB, and two patients died early before the planned TCAB. Four patients proceeded to TCAB at a median of day +104 after CD34+-PBSCT (+92 to +150). Two of these patients developed acute GVHD grades I-II (IBMTR Index B) after TCAB and all four developed chronic GVHD, which was extensive in two. With a median follow-up of 611 days (range 499-847) after transplant in the seven survivors, there have been no disease progressions, and all patients show a pattern of complete donor chimerism in bone marrow and peripheral blood.


CONCLUSIONS
The results of our pilot study suggest that this protocol produces an acceptable transplant-related morbidity and mortality in patients 45 years and older. However, there may be benefit in infusing CD34+-selected PBSCT with even lower T-cell contents and further delaying the TCAB.
Martino
R
R
Servei d'Hematologia Clínica, Hospital de la Santa Creu i Sant Pau, Av. Sant Antoni M feminine Claret, 167, 08025 Barcelona, Spain. rmartino@hsp.santpau.es
Martín-Henao
G
G
Sureda
A
A
Altés
A
A
Canals
C
C
Brunet
S
S
Sierra
J
J
D018952:Antigens, CD34 / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000628:therapy; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome
D018952:Antigens, CD34