Risk Stratification at Relapse:
The study adapted Children’s Oncology Group (COG) definitions for
risk-stratification: LR is defined as late B-ALL marrow relapse,
end-block 1 MRD <0.1% and late Isolated Extra-Medullary (IEM)
relapse, end-block 1 MRD < 0.1% ; Intermediate Risk (IR)
defined as late B-ALL marrow, end-block 1 MRD ≥ 0.1% and late IEM,
end-block 1 MRD ≥ 0.1% and High Risk patients defined as early B-ALL
marrow relapse, early IEM relapse and T-Cell All relapse irrespective of
timing and site. Late IEM relapse is defined as ≥ 18 months from
diagnosis, while early IEM is < 18 months from diagnosis and
early marrow relapse is defined as < 36 months from diagnosis
and late marrow relapse as ≥ 36 months from diagnosis.
Second Line Therapy :
Second-line therapeutic strategy was determined through study-defined
risk assessment, where in patients who were established to be resistant
to the standard 4-drug regimen were reinduced with CCG regimen-A that
involved HD-AraC (high dose cytosine arabinoside) with fludarabine or
idarubicin in six-patents, while the other six-patients with CR1
duration of 18 months re-induced with the CCG regimen B that involved
4-drug induction regimen of PVDA. Patients treated with regimen-A were
consolidated with teniposide / AraC, while patients on regimen-B were
treated with HD-ARAC /asparaginase. Post-consolidation maintenance
therapy continued for 120 weeks utilizing non-resistant drug pairs in
both the regimens in patient who were not planned to undergo
Hematopoietic Stem Cell transplantation. All patients were intended to
received CNS directed radiation therapy: patients with CNS involvement
received cranio-spinal radiation with 2400 cGy to the brain and 1200 cGy
to the spine, while patients without CNS - disease at relapse received
cranial radiation alone (1800 cGy).
In five-patients, UKALR3 regimen: dexamethasone, vincristine,
mitoxantrone, peg-asparaginase and intrathecal methotrexate was
administered; FLAG regimen with / or without idarubicin in
five-patients; REZ-BFM regimen: dexamethasone, mercaptopurine,
methotrexate, AraC and asparaginase in three-patients; St. Jude Total
XIII B HR protocol in three-patients; while, two-patients were treated
with other salvage protocols (one with ICE and one with COG 0232) and
one-patient refused therapy.
Patient stratified as HR at relapse or patients stratified as IR or LR
with resistance to first-line of salvage therapy were eligible for
allogeneic HSCT, if a suitable donor was available. Amongst the 13 out
of the 31 patients underwent HSCT, ten patients were stratified as HR,
while three patients were stratified as IR at relapse. The source of
donor were fully matched HLA (human leukocyte antigen)- identical
siblings for all patients and the conditioning regimen used
cyclophosphamide (CY) and Total Body Irradiation (TBI), while
prophylaxis for Graft-Versus-Host-Disease (GVHD) included MTX
(methotrexate) and CSA (cyclosporine).