Treatment and Assessments
The AALL02P2 chemotherapy backbone for this study has been previously
reported36 with some minor differences based on site
of relapse. Induction included 4 weeks of systemic therapy plus weekly
intrathecal triple (ITT) chemotherapy (Supplementary Table 1 ).
CNS remission was defined as two consecutive lumbar punctures with no
morphologic blasts evident on CSF analysis. Induction failure was
defined as failure to achieve CNS remission following six weekly ITT.
Following Induction, patients received Consolidation, Intensification I,
Reinduction, and Intensification II, with concomitant ITT chemotherapy.
These phases were designed to last 50 weeks, following which patients
with iCNS-R received a 3-week block of chemotherapy with 1200 cGy
cranial radiation given as 8 daily fractions of 150 cGy. AALL02P2 was
designed to allow radiation to be delayed up to 2 months to allow
completion of the intensive chemotherapy phases. Following irradiation,
patients received five 10-week cycles of intensified maintenance, each
including 4 doses of cyclophosphamide 300 mg/m2 given
weekly. Cyclophosphamide doses were omitted if the absolute neutrophil
count was <500/microliter or platelet count was
<75,000/microliter. No further intrathecal therapy was given
during maintenance, but diagnostic lumbar punctures were performed on
day 1 of each maintenance cycle.
Bone marrow samples taken prior to treatment initiation were assessed
for MRD via flow cytometry,37 at a single central
reference laboratory at the University of Washington.