The Effect of Chemotherapy Shortage in Iraq during the United Nations (UN) Sanctions on Outcome of Children with Acute Lymphocytic Leukemia (ALL).
Authors: Frangoul Haydar , Al-Jadiry Mazin F. , Shyr Yu , Shakhtour Bashar , Al-Hadad Salma A. 
Published: October 2019

Abstract
There was an increase in childhood mortality in Iraq following the UN sanctions in 1990. The sanctions created a widespread shortage of medications, particularly chemotherapy drugs. We examined the effect of chemotherapy shortage on outcome of ALL in Iraqi children. Between 1990 and 2002, 670 children with ALL were treated at Children Welfare Teaching Hospital in Baghdad. Detailed records were available for review, including documentation of missed doses of chemotherapy and reason(s) for missing it. Excluded from the analysis were patients who refused or discontinued therapy or were lost to follow up prior to the completion of therapy. ALL risk classification analysis was based on the NCI risk grouping; children were treated per the UKALL X and XI (1990–1997) and MRC 97 (1998–2002) protocols. Therapy consisted of 4 phases: induction, consolidation/interim maintenance, intensification and maintenance. Drug shortage was defined as decrease or elimination of medication solely due to unavailability of medication, and not due to myelosuppression or other toxicities. Because compliance with oral medications is subjective, our analysis was limited to intravenous medication during the first 3 phases of therapy. A Cox regression model was used to examine variables associated with outcome. There were 413 patients with standard risk (SR) disease with a median age of 4.9 years (range 1.08–9.83) and median presenting WBC of 9050 (range 400–47000), and 257 with high risk disease (HR) with a median age of 8 years (range 1.3–15) and median presenting WBC of 79300 (range 800–600000). Diagnosis of ALL was based on microscopic examination and cytochemical stains; cytogenetics and flow cytometry were not available. The median follow up for all patients is 4.8 years. For SR patients the disease free survival (DFS) and survival at 5 years are 63% and 68% respectively. In Cox regression model SR patients who received ≤ 50% of prescribed chemotherapy during induction had a significantly worse DFS (RR 0.494, 95% CI 0.30 to 0.814; p=0.0058). For HR patients the disease free survival (DFS) and survival at 5 years are 49% and 53% respectively. For HR patients those who received ≤ 50% of prescribed chemotherapy during consolidation/interim maintenance had a significantly worse DFS (RR 0.45, 95% CI 0.2018 to 1.0253; p= 0.057). Overall survival (OS) of patients who did not miss any chemotherapy due to shortage in the first 3 phases of therapy was superior in both SR (85% vs. 63%, p=0.0038) and HR patients (72% vs. 49% p= 0.018) at 5 years. The OS of children who received all chemotherapy was significantly better than those who missed any chemotherapy due to shortage at 5 years (81% vs. 58%) (p=0.0002). Despite the limited supportive care and diagnostic tools during the UN sanctions, Iraqi children who were able to receive all their intravenous chemotherapy had comparable outcome to that described in developed countries. These results suggest that dose intensity of chemotherapy is most important during induction for SR patients and during consolidation/interim maintenance therapy for HR patients.