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
Rj. Soiffer et al., 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, J CL ONCOL, 19(4), 2001, pp. 1152-1159
Purpose: The role of donor marrow T-cell depletion (TCD) in preventing graf
t-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 t
ransplant outcomes would depend on which technique is used. Herein, we repo
rt results in the first 48 recipients of unrelated marrow using CD6+ TCD as
the sole form of GVHD prophylaxis.
Patients and Methods: Median age of patients was 46 years (20 to 58 years).
Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamid
e and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engra
ftment, patients also received 7.5 Gy (22 points) or 4.5 Gy (26 points) of
total lymphoid irradiation (TLI) before admission. No additional immune sup
pressive prophylaxis was administered. Granulocyte colony-stimulating facto
r was administered daily from day +1 to engraftment.
Results: All 48 patients demonstrated neutrophil engraftment. An absolute n
eutrophil count of 500 x 10(6)/L. was achieved at a median of 12 days (rang
e, 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 0.5
7). Mortality at day 100 was 19%. There have been only five relapses. Estim
ated 2-year survival war 44% (95% CI, 0.28 to 0.59) for the entire group, 5
8% for patients less than 50 years of age. In multivariable analysis, age l
ess than 50 years (P = .002), cytomegalovirus seronegative status (P = .04)
, and early disease status at bone marrow transplant (P = .05) were associa
ted with superior survival.
Conclusion: CD6+ TCD does not impede engraftment of unrelated bone marrow a
fter low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of
GVHD prophylaxis results in on incidence of GVHD that compares favorably wi
th many adult studies of unrelated transplantation using unmanipulated marr
ow and immune-suppressive medications, especially in light of the median ag
e of our patients (46 years). Although event-free survival in patients less
than 50 years of age is very encouraging, older patients experience freque
nt transplantation-related complications despite TCD.