CD6+ donor marrow T-cell depletion as the sole form of graft-versus-host disease prophylaxis in patients undergoing allogeneic bone marrow transplant from unrelated donors.
OBJECTIVE
The role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis.


METHODS
Median age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 patients) [corrected] or 4.5 Gy (26 patients) [corrected] of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment.


RESULTS
All 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 x 10(6)/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P =.002), cytomegalovirus seronegative status (P =.04), and early disease status at bone marrow transplant (P =.05) were associated with superior survival.


CONCLUSIONS
CD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.
Soiffer
R J
RJ
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. robert_soiffer@dfci.harvard.edu
Weller
E
E
Alyea
E P
EP
Mauch
P
P
Webb
I L
IL
Fisher
D C
DC
Freedman
A S
AS
Schlossman
R L
RL
Gribben
J
J
Lee
S
S
Anderson
K C
KC
Marcus
K
K
Stone
R M
RM
Antin
J H
JH
Ritz
J
J
D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008212:Lymphocyte Depletion / Q000379:methods*; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen