Introduction:
Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in
childhood. In recent years, new potential therapeutic targets have been
found to understand leukemogenesis’s genetic and molecular structure
better. Options such as new generation monoclonal specific antibodies,
bispecific antibodies, small molecule inhibitors, chimeric antigen
receptor (CAR) T-cells have been added to treatment protocols.[1] By
evaluating pharmacokinetic and pharmacodynamic properties, survival in
ALL patients has increased to 90% in developed countries with
personalized treatment methods. In the United States, an average of 3000
children are diagnosed with ALL every year, and long-term survival has
increased to 85%-90% with current treatment methods.[2-5] The
interaction of study groups and the development of increased
risk-adapted treatment protocols over time, the addition of delayed
intensification with vincristine, L-asparaginase, dexamethasone, and
high-dose or escalating-dose methotrexate significantly improved the
prognosis.[6-9] With the addition of imatinib-mesylate to treatment
int(9:22) BCR-ABL positive (Ph-positive) leukemias, 5-year survival in
Ph-positive ALL patients has increased from 27% to 80%.[10]
As a result, the struggle and the point reached in pediatric ALL
treatment from the 1970s to the present time is a true success story.
However, there is still a long way to go. In the last 15-20 years,
excellent results have been achieved with intensive multi-agent
chemotherapeutic regimens and risk-adjusted therapy that includes stem
cell transplantation and adequate supportive care for a high-risk subset
of patients.[11, 12] In patients with ALL, levels of minimal
residual disease are indicative of the collective effect of leukemic
cell genetics, microenvironment, host factors, and chemotherapy potency
on treatment response.[13] The results of recent studies have shown
that minimal residual disease (MRD) can be used to identify patients who
can be successfully treated with low-intensity regimens, as well as
those who need intensive therapy to reduce the risk of relapse.[14]
The St Jude Total Therapy Study XV was the first clinical trial to use
MRD levels prospectively during and after remission induction therapy to
guide risk-directed treatment.[15] There were two crucial
innovations in the Total Therapy XV study. These are the complete
elimination of prophylactic cranial irradiation and the use of MRD to
guide treatment. The use of MRD to guide treatment decisions in Total
Therapy Study XV contributed significantly to the study’s overall
results by identifying patients with poor early treatment response and
possibly benefiting from additional intensified treatment.
We used the Total Therapy XV protocol with minimal modification in the
treatment of ALL patients in our center (a university hospital) in
Istanbul, the most populous city of Turkey, where the majority of the
patients are low and middle-income groups. In this study, we aimed to
present the results of our pediatric patients treated with modified St
Jude Total Therapy XV and examine our mortality rates, causes, and risk
factors.