Background: Children with incurable cancer can be treated with metronomic chemotherapy. The aim of this study was to describe the functional status in children with end-stage cancer who received metronomic chemotherapy. Procedure: An observational cohort study was designed with a convenience sample of patients younger than 18 years of age treated with metronomic chemotherapy between 2014-2020 at Hospital Civil de Guadalajara in Mexico. Results: Forty-three patients were included with a median age of 13 years. Metronomic chemotherapy was indicated most frequently in patients with lymphoblastic leukemia in ten cases (23.3%). Before metronomic chemotherapy, more than 70% of patients had disease progression after a second-line treatment. The median treatment duration was 4.2 months. Treatment was suspended in 39 patients, of which 33 patients died. The domain correlated with a lower score on the palliative performance scale at diagnosis was described in 28 cases (65.1%) according to activity level or evidence of disease, in 14 patients (32.5%) with ambulation, and in one patient (2.3%) with intake. According to their score 28/43 (65%) patients presented improvement one month after starting treatment. The McNemar test before and after one month of treatment with metronomic chemotherapy was statistically significant for these symptoms (P=0.00). We found that statistical significance was preserved during the first three months (p = 0.016) of treatment. Conclusions: The outpatient administration, good treatment adherence and few adverse effects make metronomic chemotherapy a valuable treatment option. In our experience, functional status improved significantly in the first three months of treatment.

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and despite advances in cancer treatment, there are still cases of relapse and death secondary to resistance to chemotherapy or apoptosis. One of the mechanisms is the activation of the IKK/NF-κB signaling pathway that leads to the expression of genes that interfere with apoptosis. Pentoxifylline (PTX) can block phosphorylation of IκB, thus preventing the NF-κB activity, therefore the activation of anti-apoptotic genes. Procedure: Controlled versus placebo, randomized, double-blind clinical trial. Pediatric patients with ALL during induction therapy were assigned either to pentoxifylline or the placebo group. Bone marrow aspirates were performed on day-1, day-8, day-15, and day-22. We performed flow MRD, determination of apoptosis by annexin-V/propidium iodide test, and senescence by β-galactosidase activity. Results: PTX group had higher percentage of apoptotic cells on day-8 (41.3% vs 19.4%, p=0.029), and day-15 (35.0% vs 14.2%, p <0.01). No difference was observed in the senescence determinations. On day-8, the PTX group showed MRD of 0.25% vs 18.2% (p <0.01) in the placebo group; at day-15 the PTX group showed MRD of 0.09% vs 1.4% (p=0.02). Patients with MRD <0.01% at day-8 had 3-year OS of 81.6% vs 58.3% (p=0.03); at day-15 patients with MRD <0.01% at day-8 had 3-year OS of 77.9% vs 54.5% (p=0.03). Conclusion: PTX group showed a MRD <0.01% earlier, on day-8 and 15, and presented a higher percentage of apoptotic cells. In the entire cohort, patients with MRD <0.01% on day 8 or 15 showed better OS.