A 17-year experience with ALL-BFM protocol in acute lymphoblastic leukemia: Prognostic predictors and interruptions during protocol
Introduction
Acute lymphoblastic leukemia (ALL) is the most common malignant tumor of childhood and it is the fourth most common cause of mortality in children between 1 and 15 years in Turkey [1]. Almost 4000 new ALL cases are diagnosed annually in USA and the cure rates are about 80% to 90% in developed countries [2]. Significant progress has been made in the management of ALL patients with combination of effective anti-leukemic drugs and risk stratification of patients at the onset of therapy enabled treatment intensification for high risk patients. Currently, efforts are made toward decreasing the dose of chemotherapy applied, in order to prevent long-term complications, while preserving and even further improving the disease-free survival.
There are considerable differences between Western countries and developing countries for ALL, including age at diagnosis, immunophenotypes, death and relapse rates, causes of mortality, complications, and compliance to treatment. Unfortunately, data regarding the long term follow up of large patient cohorts from developing countries are so scarce.
Several clinical and biologic prognostic parameters have been established to predict outcome in ALL patients. Among these, age, white blood cell (WBC) count at diagnosis, immunophenotype, cytogenetic features of blasts, extramedullary involvement, prednisone response, complete remission at the end of induction therapy, and minimal residual disease (MRD) have been well-characterized in clinical trials [3]. More recently, individual response of nonmalignant hematologic cells to chemotherapy and the ability of nonneoplastic hematopoietic precursors to restore hematopoiesis early in the treatment were suggested as novel prognostic predictors in ALL [4], [5], [6], [7]. The ease of assessment of their levels with simple serial complete blood counts make them valuable prognostic parameters for use in developing countries. However, their validity and reliability in predicting disease outcome are highly debated and these markers have never been formally assessed in Turkish ALL patients.
The aim of this study is to retrospectively analyze all ALL patients who were treated in a single tertiary center of Turkey to investigate prognostic parameters which can be used to predict disease outcome and present the results of our modified Berlin-Frankfurt-Münster (BFM) 95 treatment protocol.
Section snippets
Patient selection
The study included pediatric patients under 18 years old who were diagnosed with ALL in Istanbul University Cerrahpasa School of Medicine and treated between January 1995 and August 2012. Patients treated with protocols other than BFM and cases who were referred to other tertiary centers during induction phase were excluded.
Diagnosis
The diagnosis of ALL was made if blast count in bone marrow was 25% or more. Peripheral blood and bone marrow smears were stained with May–Grünwald–Giemsa and evaluated
Results
A total of 242 patients were included in the study whose characteristics are summarized in Table 2. Mean age at diagnosis was 6.18 years with a male:female ratio of 1.46. Among them, 74% of the cases had common B-ALL, while 18% had T-ALL, 5% had pre-B ALL, and 3% had pro-B ALL. One-hundred-and-thirty-seven cases (56.6%) were classified in MRG, 65 (26.9%) were in SRG, and 40 (16.5%) were in HRG. Overall, 171 out of 242 patients (70.6%) had extramedullary involvement at diagnosis, with liver
Discussion
In this study, we retrospectively analyzed the prognostic factors and problems appeared during ALL treatment in a large cohort of patients consecutively diagnosed in a large tertiary center of Turkey. Age older than 10 years, being in HRG, spleen, CNS, bone, and eye involvement, t(9;22), prednisone response, bone marrow response at days 15 and 33, low day 15 platelet count, low day 33 lymphocyte, monocyte, and platelet counts, treatment delay less than 11 days, sepsis during treatment, and
Conflict of interest statement
The authors declare no conflicts of interest or sources of funding.
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