Correspondence

Shortage of Chemotherapeutic Agents in Iraq and Outcome of Childhood Acute Lymphocytic Leukemia, 1990–2002

N Engl J Med 2008; 359:435-437July 24, 2008

Article

To the Editor:

The United Nations (UN) imposed economic sanctions against Iraq in 1990, after the invasion of Kuwait, which remained in effect until 2003. During the sanctions, there was a widespread shortage of medications, including antibiotics and chemotherapeutic agents, and basic services.1,2 We sought to determine the effect of the shortage of chemotherapeutic agents on the outcome of acute lymphocytic leukemia (ALL) in Iraqi children during the period of UN sanctions.

A total of 651 children with ALL who were treated at the Children's Welfare Teaching Hospital in Baghdad and who had complete medical records were included in this analysis. There were 408 patients with standard-risk disease, with a median age of 4.9 years (range, 1.1 to 9.8) and a median white-cell count at presentation of 9050 per cubic millimeter (range, 400 to 47,000). The remaining 243 patients were at high risk and had a median age of 8 years (range, 1.3 to 15.0) and a median white-cell count at presentation of 78,600 per cubic millimeter (range, 800 to 600,000). All children were treated according to the UKALL X and XI protocols (between 1990 and 1997) and the Medical Research Council ALL 97 protocol (between 1998 and 2002).3,4 Medication shortage was defined as no treatment or incomplete treatment owing to unavailability of chemotherapeutic agents. The absence of chemotherapy administration or decreased or delayed administration due to toxic effects or myelosuppression was not considered to be a medication shortage.

The shortage of chemotherapeutic agents was evident from the increase in the proportion of the 651 patients who received less than 50% of the prescribed chemotherapy: 20.1% between 1990 and 1994 to 54.3% between 2000 and 2002. With a median follow-up period of 8.4 years (range, 3.5 to 16.9), the overall survival rate for patients who received all prescribed chemotherapy was significantly greater than that for patients who missed any chemotherapy (P<0.001). This difference was also significant within the standard-risk group (P=0.004) and within the high-risk group (P=0.02) (Figure 1Figure 1Overall Survival Rates among Children with Acute Lymphocytic Leukemia in Iraq, According to Whether All Prescribed Chemotherapy Was Administered.). In a multivariate analysis of the data (including age, white-cell count at presentation, hemoglobin level, presence or absence of organomegaly, and year of treatment), as compared with receipt of all chemotherapy, missed chemotherapy was associated with a significantly worse outcome within the standard-risk group (relative risk, 2.90, 95% confidence interval [CI], 1.41 to 6.22; P=0.005) and within the high-risk group (relative risk, 2.55; 95% CI, 1.29 to 5.18; P=0.008). Relapse was the most common cause of treatment failure, occurring in 217 of the 651 patients (33.3%). There was a significant inverse relationship between the amount of prescribed chemotherapy that was administered and the risk of relapse (relative risk, 0.96, 95% CI, 0.93 to 0.99; P=0.01) (i.e., the more prescribed chemotherapy received, the lower the risk of relapse).

Despite the lack of flow cytometry, cytogenetic evaluation, and aggressive supportive care, the outcomes for children who could receive all their prescribed chemotherapy were similar to those found in developed countries.3 Our findings reinforce the concept that the most important factor in improving survival, even in children with leukemia, is adequate treatment.

Haydar Frangoul, M.D.
Vanderbilt University School of Medicine, Nashville, TN 37232-6310
haydar.frangoul@vanderbilt.edu

Mazin F. Al-Jadiry, M.D.
Baghdad Medical College, Baghdad, Iraq

Yu Shyr, Ph.D.
Fei Ye, Ph.D.
Bashar Shakhtour, M.S.
Vanderbilt University School of Medicine, Nashville, TN 37232-6310

Salma A. Al-Hadad, M.D.
Baghdad Medical College, Baghdad, Iraq

4 References

1. 1

   Akunjee M, Ali A. Healthcare under sanctions in Iraq: an elective experience. Med Confl Surviv 2002;18:249-257
   CrossRef | Medline

2. 2

   Sansom C. The ghost of Saddam and UN sanctions. Lancet Oncol 2004;5:143-145
   CrossRef | Web of Science | Medline

3. 3

   Chessells JM, Bailey CC, Richards S. MRC UKALL X: the UK protocol for childhood ALL: 1985-1990. Leukemia 1992;6:157-161
   Web of Science | Medline

4. 4

   Kalmanti M, Karamolegou K, Mikraki V, et al. Efficacy and toxicity of UKALL-X in childhood ALL. Med Pediatr Oncol 1988;16:390-391
   

Citing Articles (2)

Citing Articles

1. 1

   Lika'a Fasih Y. Al-Kzayer, Kazuo Sakashita, Kazuyuki Matsuda, Salma Abbas Al-Hadad, Mazin Faisal Al-Jadiry, Wisam Majeed Abed, Jaafar M.H. Abdulkadhim, Tariq Abadi Al-Shujairi, Janan Ghalib Hasan, Hussam M. Salih Al-Abdullah, Mouroge H. Al-Ani, Paiman Ali I. Saber, Toshi Inoshita, Minoru Kamata, Kenichi Koike. (2012) Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards. Pediatric Blood & Cancern/a-n/a
   CrossRef

2. 2

   Maria Luisa Moleti, Salma Abbas Al-Hadad, Mazin Faisal Al-Jadiry, Amir Fadhil Al-Darraji, Raghad Majid Al-Saeed, Annalisa De Vellis, Alfonso Piciocchi, Stefania Uccini, Robin Foà, Anna Maria Testi. (2011) Treatment of children with B-cell non-Hodgkin lymphoma in a low-income country. Pediatric Blood & Cancer 56:4, 560-567
   CrossRef