A. Balduzzi et al., Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions, LEUKEMIA, 15(1), 2001, pp. 50-56
Autologous transplantation is a treatment option for relapsed childhood acu
te lymphoblastic leukemia (ALL) in second complete remission (CR2) when a s
uitable donor is not available. In an attempt to prevent relapses originati
ng from graft leukemic contamination, the experimental protocol of in vitro
purification of leukapheretic products with monoclonal antibodies (MoAbs),
previously reported for adults, was adopted in 11 of 12 consecutive patien
ts (median age, 9 years) with B cell precursor ALL in CR2 after late relaps
e (median, 37; range, 31-51 months after the onset) enrolled between July 1
997 and July 1999 at a single pediatric center. At a median of 12 days afte
r the mobilizing chemotherapy followed by G-CSF, a median of 13.9 (range, 5
.9-18.7)x 10(6) CD34(+) cells/kg were collected from each patient and a med
ian of 7.5 (range, 4.1-12.6) x 10(6) CD34(+) cells/kg underwent the purific
ation procedure. The first step of immuno-rosetting allowed a one-log reduc
tion of the total cell count, by eliminating more than 90% of the CD11b(+)
cells; the second step, performed after incubation with anti-CD19 MoAbs, al
lowed the depletion of 99% (range, 93-100) of the CD19(+) cells, kept withi
n the magnetic field of the immunodepletion column, with a median recovery
of 73% (range, 55-87) of the collected CD34(+) cells. Molecular analysis as
sessed the in vitro eradication of detectable leukemic cells. A median rein
fusion of 5.2 (range, 3.2-9.1) x 10(6) CD34(+) cells/kg for each patient (m
edian viability, 90%), after conditioning with the 'TBI-VP16-CY' regimen, a
llowed prompt engraftment and immunological reconstitution; no patients exp
erienced severe transplant-related toxicity or major infections. One patien
t relapsed 7 months after transplantation, while 10 patients are alive in c
linical and molecular remission, at a median follow-up of 29 months (range,
15-40) (2-year EFS, 89%, s,e, 9), In conclusion, the procedure proved to b
e reproducible for pediatric purified autografting, highly efficient concer
ning stem cell recovery acid depletion of leukemia-lineage specific cells,
and promising in terms of final outcome.