A strategy to improve treatment‐related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays

Background

Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world.

Procedure

A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact.

Results

The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries.

Conclusions

Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.     

Hypokalemia after theophylline intoxication. The effects of acute vs chronic poisoning

To characterize the frequency and pattern of hypokalemia (serum potassium level less than 3.5 mmol/L) after theophylline poisoning, we prospectively evaluated 88 consecutive patients with theophylline intoxication (serum theophylline concentration greater than or equal to 0.165 mmol/L). This mean admission serum theophylline concentration of this cohort was 0.331 mmol/L, with a range of 0.165 to 0.982 mmol/L. The simultaneous mean serum potassium concentration was 3.36 mmol/L (range, 2.20 to 5.80 mmol/L). Fifty-three patients (60%) were hypokalemic on hospital arrival. When, on the basis of recent ingestion, patients were separated into acute, chronic, or acute-on-chronic categories of theophylline intoxication, significant differences in serum potassium were found: Patients with acute theophylline intoxication had a mean serum potassium concentration of 2.94 mmol/L; 85% were hypokalemic. In contrast, patients with chronic theophylline intoxication had a mean serum potassium concentration of 3.83 mmol/L, with a 32% frequently of hypokalemia. These data demonstrate that hypokalemia is common after theophylline intoxication and has a significantly higher incidence after acute overdose. The difference in the frequency of hypokalemia between patients with acute vs chronic intoxication has unclear origins but may be related to the disparities in clinical course (particularly the appearance of seizures and cardiac arrhythmias) that have been observed after acute vs chronic theophylline intoxication.