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.