HIGH INFECTION RELATED MORTALITY IN PAKISTANI CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKAEMIA DURING REMISSION INDUCTION CHEMOTHERAPY: REVIEW OF DATA FROM A SINGLE INSTITUTION
Abstract
Purpose: Despite advances in the treatment of acute lymphoblastic leukaemia (A.L.L.), the outcome for children living in the developing countries is still poor. This is in large part due to high treatment-related mortality (TRM). This study was carried out to review the data and analyze the factors resulting in high TRM during remission induction chemotherapy.
Methods: Data for children treated at our centre during the calendar year 2007 were retrospectively analysed. Standard four-drug induction chemotherapy was used without risk strati cation. Bone marrow evaluation was carried out at days 8 and 28. Cerebrospinal uid analysis was carried out on day 1 and with each subsequent intrathecal chemotherapy injection. Modern supportive care facilities including antibiotics, nutritional support and intensive care unit were available.
Results: Eighty-one children were eligible for analysis. Median age was 5 years (range 2–16), 72% were male with M:F ratio of 2.5:1. Seventy- five (92%) children had precursor B-cell A.L.L. Only 2 children had central nervous system leukaemia at presentation. Median presenting white blood cell count was 8.83 (range: 1–446). Severe malnutrition (weight <5th centile for age) was seen in 42% of children. Median symptom duration was 6 (range 1–30) weeks at the time of presentation. Induction mortality was 25%. Induction mortality was 25.6% (n = 21). Twenty were related to infections, while more than half (52%) occurred as a result of an outbreak of Acinetobacter infection. Severe malnutrition and Acinetobacter infection (due to an outbreak in our unit during the study period) were highly predictive of TRM during remission induction chemotherapy.
Conclusions: Infection control measures, health education and reduction in treatment intensity may improve survival for children with A.L.L. in Pakistani population.
Key words: Acute lymphoblastic leukaemia in children, malnutrition, Pakistan, treatment-related mortality
References
Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008;371:1030-43.
Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006;354:166-78.
Silverman LB, Gelber RD, Dalton VK, et al. Improved outcome for children with acute lymphoblastic leukemia: Results of Dana Farber consortium protocol 91-01. Blood 2001; 97:1211-8.
Mejía-Aranguré JM, Fajardo-Gutiérrez A, Reyes-Ruíz NI, et al. Malnutrition in childhood lymphoblastic leukemia: A predictor of early mortality during the induction-to- remission phase of the treatment. Arch Med Res 1999; 30:150-3.
Gupta S, Bonilla M, Fuentes SL, et al. Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in el salvador. Br J Cancer 2009;100:1026-31.
de Haas V, Breunis WB, Verhagen OJ, et al. Accurate quantification of minimal residual disease at day 15, by real-time quantitative polymerase chain reavtion identi es alsopatientswithB-precursoracutelymphoblasticleukemia at high risk for relapse. Blood 2000;96:1619-20.
Pui CH, Sandlund JT, Pei D, et al. Improved outcome for children with acute lymphoblastic leukemia: Results of total therapy study XIIIB at St Jude children’s research hospital. Blood 2004;104:2690-6.
Aziz Z, Zahid M, Mahmood R, et al. Modi ed BFM protocol for childhood acute lymphoblastic leukemia: A retrospective analysis. Med Pediatr Oncol 1997;28:48-53.
Khalid S, Moiz B, Adil SN, et al. Retrospective review of pediatric patients with acute lymphoblastic leukemia: A single center experience. Indian J Pathol Microbiol 2010; 53:704-10.
Gao YJ, Lu FJ, Wang HS. Treating childhood acute lymphoblastic leukemia in a developing country 1998-2003: The experience of a single children’s hospital in China. J Pediatr Hematol Oncol 2006;28:798-802.
Advani S, Pai S, Venzon D, et al. Acute lymphoblastic leukemia in India: An analysis of prognostic factors using a single treatment regimen. Ann Oncol 1999;10:167-76.
Magrath I, Shanta V, Advani S, et al. Treatment of acute lymphoblastic leukaemia in countries with limited resources; lessons from use of a single protocol in India over a twenty year period [corrected]. Eur J Cancer 2005;41:1570-83.
Kulkarni KP, Marwaha RK, Trehan A, et al. Survival outcome in childhood ALL: Experience from a tertiary care centre in north India. Pediatr Blood Cancer 2009;53:168-73.
Gales AC, Jones RN, Forward KR, et al. Emerging importance of multidrug-resistant acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: Geographic patterns, epidemiological features, and trends in the SENTRY antimicrobial surveillance program (1997-1999). Clin Infect Dis 2001;32 Suppl 2:S104-13.
Barr RD, Gibson BE. Nutritional status and cancer in childhood. J Pediatr Hematol Oncol 2000;22:491-4.
Barr RD, Ruiz-Argüelles GJ. Nutrition and cancer in children. Med Pediatr Oncol 2003;41:54-7.
Pinkel D. Selecting treatment for children with acute lymphoblastic leukemia. J Clin Oncol 1996;14:4-6.
Siraj AK,Kamat S,Gutiérrez MI,etal. Frequencies of the major subgroups of precursor B-cell acute lymphoblastic leukemia in Indian children differ from the west. Leukemia 2003; 17:1192-3.
FaizM,QaziJI.T(12:21)isunderrepresentedinchildhood B-lineage acute lymphoblastic leukemia in Punjab, Pakistan. J Pediatr Hematol Oncol 2010;32:249-51.
Mitchell CD, Richards SM, Kinsey SE, et al. Bene t of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: Results of the UK medical research council ALL97 randomized trial. Br J Haematol 2005; 129:734-45.
Belgaumi AF, Al-Bakrah M, Al-Mahr M, et al. Dexamethasone associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin. Cancer 2003; 97:2898-903.
Hurwitz CA, Silverman LB, Schorin MA, et al. Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia. Cancer 2000;88:1964 9.
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