Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor.

OBJECTIVE: Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL) of childhood; it is more frequent among high-risk patients from low-middle income than from high-income countries. The frequency, sites and outcome of relapsed ALL in children of northeast Mexico over a decade was documented. METHODS: A retrospective analysis of 246 children belonging to a low-income group <16 years with de novo ALL during 2004-2015 was performed. Five-year overall survival (OS) and event-free survival was estimated by Kaplan-Meier analysis. Data on time, site, response to therapy and final outcome of relapse were analyzed. Hazard ratios (HRs) of relapse and death were estimated by the Cox regression model. Very early relapse was defined as that occurring in <18 months, early relapse between 18 and 36 months, and late relapse >36 months from diagnosis, respectively. RESULTS: Eighty-seven (35.4%) children relapsed. Five-year OS was 82.6% in children without relapse vs. 42% for relapsed patients. Bone marrow (BM) was the most frequent site of relapse (51.72%). Isolated central nervous system (CNS) relapses occurred in 29.9%. Five-year OS was 11.2% for BM and 15.5% for early relapse. HR of relapse for organomegaly was 3.683, 2.247 for an initial white blood cell count >50 000 × 109/l and 1.169 for positive minimal residual disease status. CONCLUSION: A high rate of very early, CNS, and BM relapse with a considerably low 5-year OS requiring reassessment of therapy was documented. Organomegaly at diagnosis was a highly significant clinical predictor for relapse.

TNF-α increases in the CSF of children with acute lymphoblastic leukemia before CNS relapse.

There is scarce information regarding the concentration of cytokines in cerebrospinal fluid (CSF) of children with acute lymphoblastic leukemia (ALL) and their clinical association with CNS status. A prospective analysis of 40 patients <18years with newly diagnosed ALL was performed. Human cytokine magnetic bead panel assay values of IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, TNF-α in CSF at diagnosis, end of induction to remission, and 6months after diagnosis were determined. IL-6 and MCP-1 values showed a significant increment at the end of induction. From the whole group 4 (10.0%), patients relapsed to the CNS at a median of 11.48months. A significantly higher value of TNF-α at third determination in these CNS-relapsed patients was documented, 7.48 vs. 2.86pg/mL in 36 children without relapse (p=0.024). TNF-α concentration increased at a median 5.48months before CNS relapse. By receiver-operating characteristic curve (ROC) analysis, the best cut-off point of TNF-α concentration that better predicted CNS relapse was ≥1.79pg/mL. In conclusion an increase in TNF-α concentration on CSF preceded CNS relapse in children with ALL. An increase in MCP-1 and IL-6 was not associated to CNS relapse and appears to result from an inflammatory response after IT injection of chemotherapy.

Results of Treating Childhood Acute Lymphoblastic Leukemia in a Low-middle Income Country: 10 Year Experience in Northeast Mexico.

BACKGROUND AND AIMS: In high-income countries, treatment protocols for acute lymphoblastic leukemia (ALL) in children lead to a 5-year overall survival (OS) approaching 90%. There is scarce information on protocols and results of therapy from low-middle income countries (LMIC). We documented the results of treating children with ALL with two protocols in consecutive 5-year periods at a reference center in northeast Mexico. PATIENTS AND METHODS: Children ≤16 years of age diagnosed with ALL treated with two protocols were studied. Each protocol was used for 5 years; 246 children, 112 in protocol 1 and 134 in protocol 2, were included. Protocols were BFM-inspired and adapted from several regimens; protocol 2 was intended to decrease toxicity and need for hospitalization. Event-free survival (EFS) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: In protocol 1, 103 patients (91.96%) achieved complete remission compared to 106 (79.10%) in protocol 2 (p = 0.001). The 5-year OS was 67.1% for protocol 1 vs. 55.5% for protocol 2, whereas EFS was 58.2% vs. 36.9%, respectively. Relapse occurred in 45 patients (40.17%) in protocol 1 vs. 42 (31.34%) in protocol 2 (p = 0.181). OS 1 year after relapse was 52.4% vs. 57.1%, respectively. No difference in relapse rate was documented. CONCLUSIONS: No improvement in survival rates of children with ALL from a low-income group living in a LMIC was achieved over a decade. Implementation of contemporary protocols with a high success rate is mandatory.

Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era?

BACKGROUND: Low-dose all-transretinoic acid (LD-ATRA) has shown similar peak plasma concentrations and a mean area under the concentration time curve in comparison with standard doses of ATRA. We evaluated the efficacy of LD-ATRA plus anthracycline-based chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Patients diagnosed with APL during the period of 2002 to 2014 were included. They received ATRA 25 mg/m(2) plus anthracycline (doxorubicin or mitoxantrone) as induction chemotherapy, followed by 3 consolidations with LD-ATRA and anthracycline and maintenance therapy with intermittent LD-ATRA and oral chemotherapy for 2 years. RESULTS: Twenty-two patients with a median age of 28 years (range, 18-55 years) were included; 17 (77%) were in the low-risk group. Complete remission occurred in 86%, and the early death rate was 9%. At a median follow-up of 32 months (range, 4-126 months) disease-free survival (DFS) was 75% and overall survival (OS) was 86%, with a relapse rate of 27% for the entire follow-up period. CONCLUSION: LD-ATRA plus anthracycline is safe and effective in achieving CR of APL. The early death rate is similar to that of treatment with standard doses, but it appears to be inferior in preventing relapses.

Efficacy of mitoxantrone as frontline anthracycline during induction therapy in adults with newly diagnosed acute lymphoblastic leukemia: a single-center experience.

Remission induction regimens for acute lymphoblastic leukemia (ALL) in adults induce complete remission (CR) in 60-90% and cure in 20-40%. A cohort study of newly diagnosed patients with ALL treated with mitoxantrone versus doxorubicin was conducted from 2005 to 2013. The primary endpoint was the proportion of CR. Eighty-five patients were included. Fifty-three received induction with doxorubicin and 32 with mitoxantrone. Median follow-up in the cohort was 40.2 months (range 2-95). Twenty-nine patients (90.6%) achieved CR in the mitoxantrone arm compared with 37 (69.8%) in the doxorubicin group (p = 0.032). There was no difference in death or relapse rate (p = 0.095 and 0.075), hematological recovery (p = 0.654), incidence of adverse events (p = 0.6), in-hospital days during induction (p = 0.456) or overall survival (p = 0.105). Induction toxicities were comparable. Mitoxantrone can be safely and effectively used as a frontline anthracycline in adults newly diagnosed with ALL.

Characteristics and clinical evolution of patients with acute myeloblastic leukemia in northeast Mexico: an eight-year experience at a university hospital.

BACKGROUND/OBJECTIVE: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We documented the characteristics and results of treatment of patients with AML at a single reference center. METHODS: Patients diagnosed with AML between June 2003 and July 2011 at a university hospital in northeast Mexico were studied. Overall survival (OS) and event-free survival (EFS) were determined, and risk factors were analyzed with respect to their influence on prognosis. RESULTS: A total of 132 AML patients were included. Median age was 32 years. Complete remission (CR) was achieved by 55% of patients. CR was achieved by 65.1% of patients <60 years (n = 109), compared to 8.7% of those >60 years (n = 23; p < 0.001). In all, 39% of patients >60 years suffered an early death, compared to 14.7% of those <60 years (p < 0.001). OS for patients with AML was 35%, whereas EFS was 32%. On multivariate analysis, patients >60 years had a lower OS and EFS (p < 0.001). A total of 28% of patients received a transplant, and they had high er OS and EFS. Conclusions: Our patients were considerably younger and had remarkably lower survival rates than reported for other populations; those >60 years had a higher early death rate, and fewer of these patients achieved CR.