Acute Leukemias - Republican Scientific Medical Library

156 Chapter 11 · Conventional Therapy in Adult Acute Lymphoblastic Leukemia: Review of the LALA Program
Fig. 11.10. Overall outline of GRAAPH-05 protocol. Abbreviations:
AlloSCT, allogeneic stem cell transplantation; AutoSCT, autologous
stem cell transplantation; MRD, minimal residual disease (* decisional,
** not decisional); CPM, cyclophosphamide; DXM, dxamethasone;
DXR, doxorubicin; G-CSF, granulocyte colony-stimulating
Early response to initial therapy (response to corticosteroid
prephase and response to chemotherapy at
day 8) was not correlated to baseline high-risk factors
and should be considered in further adult ALL studies.
The evaluation of morphological early response correlated
closely with postinduction MDR measurement.
The hyperfractionated cyclophosphamide (HyperC) reinforcement
in patients with a poor early response appeared
to be a promising approach to improve their outcome
and will be randomly tested in the further
GRAALL-05 study.
In the LALA-94 trial, negative BCR-ABL MRD and
allogeneic donor availability were two independent
good-risk factors for survival in Philadelphia-positive
ALL patients reaching hematologic CR after standard
induction followed by intensive HAM consolidation
[25]. In a phase 1/2 study initiated in 2003, we combined
increasing dosages of imatinib mesylate with HAM with
an attempt to increase the fraction of patients achieving
molecular remission, and to evaluate the safety of the
combination regimen and the feasibility of autologous
peripheral blood stem cell collection after HAM [63].
The recommended dosage of imatinib was 600 mg per
day for further combinations of imatinib and intensive
chemotherapy. After HAM, peripheral blood stem cell
collection was feasible under imatinib administration.
factor; HDAC, high-dose cytarabine; HDMTX, high-dose methotrexate;
HyperCVAD, regimen of hyperfractionated cyclophosphamide,
vincristine, doxorubicin, and dexamethasone; IM, imatinib mesylate;
IT, intrathecal; MFD, matched familial donor; MUD, matched unrelated
donor; PDN, prednisone; VCR, vincristine.
Failure to improve the molecular remission rate as compared
to our historical control could be explained by the
relatively short exposure to imatinib and/or by the absence
of in vivo synergism between imatinib and cytarabine
or mitoxantrone. More benefit might be anticipated
by incorporating imatinib early in the treatment.
This is currently tested in the GRAAPH-05 (Fig. 11.10)
comparing an induction therapy “based” on imatinib
to an induction therapy combining the regimen of hyperfractionated
cyclophosphamide, vincristine, doxorubicin,
and dexamethasone (HyperCVAD) chemotherapy
with imatinib as conceived by the M.D. Anderson Cancer
Center [64, 65].
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