A randomized multicenter comparison of CD34(+)-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies.
OBJECTIVE
Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34(+) selection for T-cell depletion (TCD) in both study arms.


METHODS
Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms.


RESULTS
Recipients of PBPC received more CD3(+) T cells (median: 3.0 vs 2.0 x 10(5)/kg, p<0.0001) and more CD34(+) cells (median: 3.6 vs 0.9 x 10(6)/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II-IV was 37% after BMT vs 52% after PBPCT and was most significantly (p=0.007) affected by the number of CD3(+) T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34(+) cells were associated with less TRM. With a median follow-up of 37 months (range: 12-75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT (p=0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2 x 10(5)/kg.


CONCLUSIONS
Outcome following T cell-depleted PBPCT critically depends on the number of CD3(+) T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34(+) cell numbers.
Cornelissen
Jan J
JJ
Department of Hematology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. j.cornelissen@erasmusmc.nl
van der Holt
Bronno
B
Petersen
Eefke J
EJ
Vindelov
Lars
L
Russel
Charlotte A
CA
Höglund
Martin
M
Maertens
Johan
J
Schouten
Harry C
HC
Braakman
Eric
E
Steijaert
Monique M C
MM
Zijlmans
Mark J M
MJ
Slaper-Cortenbach
Ineke
I
Boogaerts
Marc A
MA
Löwenberg
Bob
B
Verdonck
Leo F
LF
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000032:analysis; D002469:Cell Separation; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D017252:CD3 Complex