NEW CONSECUTIVE HIGH-DOSE CHEMOTHERAPY MODALITY WITH FRACTIONATED BLOOD STEM-CELL SUPPORT IN THE TREATMENT OF HIGH-RISK PEDIATRIC SOLID TUMORS - A FEASIBILITY STUDY
T. Kajiume et al., NEW CONSECUTIVE HIGH-DOSE CHEMOTHERAPY MODALITY WITH FRACTIONATED BLOOD STEM-CELL SUPPORT IN THE TREATMENT OF HIGH-RISK PEDIATRIC SOLID TUMORS - A FEASIBILITY STUDY, Bone marrow transplantation, 21(2), 1998, pp. 147-151
For the treatment of childhood solid tumors, we performed a pilot feas
ibility study of consecutive high-dose therapies, in which each course
was followed by transplantation with granulocyte colony-stimulating f
actor-mobilized peripheral blood cells which had been separated into C
D34-positive and -negative fractions by an Isolex system (Baxter), Pos
itive selection of CD34(+) cells has been associated with inevitable c
ell loss, To overcome this loss, CD34(+) cells that had migrated into
the negative fraction were saved and used for the first transplant, wh
ich was followed by a second transplant after a 3- to 5-month interval
, In this phase I feasibility study, the results in six children were
evaluated for safety and engraftment, Multi-drug cytoreductive regimen
s using ranimustine (MCNU), melphalan, thiotepa, carboplatin, cyclopho
sphamide or VP-16 were comparable between the two transplant procedure
s in terms of their intensity. The number of CD34(+) cells in the 'CD3
4((+)) fraction' was 3.31 x 10(6)/kg (0.63-4.3 x 10(6)/kg), while this
number in the 'CD34((-)) fraction' could not be evaluated correctly d
ue their scarcity (< 0.1%). The median numbers of infused MNC and CFU-
GM were, respectively, 4.2 x 10(6)/kg and 1.75 x 10(5)/kg in the CD34(
+) fraction, and 4.8 x 10(8)/kg and 3.35 x 10(5)/kg in the CD34((-)) f
raction, The number of days required to achieve an ANC > 0.5 x 10(9)/l
and a platelet count > 20 x 10(9)/l and > 50 x 10(9)/l were, respecti
vely, 14.5, 15.0 and 19.5 in the first transplant with CD34(-) cells,
and 13.5, 18.0 and 25.0 in the second transplant with CD34(+) cells, w
ith no essential difference between the two treatments, Although the s
mall number of patients, the variation in clinical status and treatmen
t, and the short follow-up invalidate any evaluation of the therapeuti
c benefit of this strategy, the encouraging results support the feasib
ility of this strategy, which enables an escalation of dose intensity
with an improved cost/benefit ratio.