Pediatr Blood Cancer 2015;62:1700–1708 Clinical Features and Induction Outcome of Childhood Acute Lymphoblastic Leukemia in a Lower/Middle Income Population: A Multi-Institutional Report From Pakistan Zehra Fadoo, MBBS, DABP, 1 * Imran Nisar, MBBS, MSc, 1 Fatimah Yousuf, 2 Laila Saleem Lakhani, 2 Shamvil Ashraf, MBBS, FCPS, MRCP, 3 Uzma Imam, MBBS, 4 Junaid Zaheer, MBBS, 1 Ahmed Naqvi, MBBS, MCPS, MRCP (UK), FRCPCH (UK), 5 and Asim Belgaumi, MD 1,6 INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It constitutes approximately 25% of cancers in children below 15 and 19% in children below 20 years of age.[1–3] The annual incidence of ALL in Western and Eastern European countries are similar with figures of 40 and 30–35 cases per million children, respectively; the incidence in Sub-Saharan Africa is reportedly lower, at 20 cases per million children.[4,5] Incidence rates from many developing countries in Asia are unavailable as national cancer registries are not established there. Although data are not available from all parts of India, reports from various Indian cancer registries indicate that approximately 10,000 new cases of ALL are diagnosed in their population of less than 25 years of age. [6] Several risk determining variables have been identified in childhood ALL and include patient-specific, clinical, and genetic features. Age and white blood cell (WBC) count have been used to stratify patients at presentation into prognostic strata. Additionally, the presence of extramedullary involvement and specific genetic lesions in the leukemic clone are used to determine risk for relapse and consequently assignment of appropriately intensive therapy.[7,8] While the proportions of these risk-determining variables are well characterized in most western populations, these data are only now becoming available in developing countries. What is evident is that there are regional and ethnic differences in their prevalence and these differences may impact on the outcomes of ALL therapy. Outcome of patients with ALL is related not only to the leukemia itself, but also to infectious and toxic morbidities and mortality. This is especially true during induction therapy and has been demonstrated by a study from St. Jude Children’s Research Hospital which concluded that infectious causes contributed to 80% of the deaths observed in children with ALL during the induction phase.[9] A study from Pakistan has also demonstrated that in their cohort of ALL patients 85% of all deaths occurred due to infections. [10] However, the overall mortality was quite high, with 12.8% patients dying during induction therapy, suggesting an influence of socio-economic conditions and co-morbidities on patient outcome.[9] There are few data on ALL characteristics and outcome of early therapy from low and middle-income countries (LMICs), such as Pakistan. Most information available is from single-institution retrospective studies. Our aims were to determine the spectrum of the presenting clinical features and prognostic factors in children with ALL and determine the outcome of induction therapy in a multi-institutional prospective study. Background. Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood. Some evidence suggests differences in clinical and cytogenetic characteristics of ALL based on geographic and ethnic variations. However, data on ALL characteristics and early outcome of therapy from low/middle-income countries such as Pakistan are scanty. Procedure. A prospective, multi-institutional cohort study in Karachi enrolled 646 newly diagnosed children with ALL over 3 years. Standard forms were used to collect demographic, clinical, and laboratory data at presentation and at the end of induction. Results. Of the total, 66.1% (n ¼ 427) were males. Median age was 6 (mean  SE 6.87  0.16; range 0.16–18) years. The most common clinical presentation was fever (88.7%). BPC-ALL was diagnosed in 78.5%, while 17.5% had T-ALL; 28.8% had a WBC >50  10 9 /L. With 316 patients karyotyped, hypodiploidy and hyperdiploidy were seen in 5.1% and 10.7%, respectively. Of those tested, ETV6-RUNX1 translocation was detected in 13.2%, while BCR-ABL1 translocation and MLL gene rearrangements were seen in 7.3% and 4.6%, respectively. The cumulative loss to follow up before and during induction was 12.8% (n ¼ 83) and 11.5% (n ¼ 74) died before or during this phase. Induction was successfully completed by only 75.6% (n ¼ 489) of the entire cohort and 69.6% (n ¼ 450) achieved remission. Conclusion. These patients had ALL with higher risk features than that reported from developed countries. One quarter failed to complete induction chemotherapy. This suboptimal result requires further study and development of innovative interventions, particularly focusing on the causes and solutions for late referral, abandonment, and infections. Pediatr Blood Cancer 2015;62:1700–1708. # 2015 Wiley Periodicals, Inc. Key words: childhood ALL; induction outcome; low/middle income country 1 Department of Pediatrics and Child Health and Department of Oncology, Aga Khan University, Karachi, Pakistan; 2 Medical Student, Aga Khan University Medical College, Pakistan; 3 Children’s Cancer Hospital, Karachi, Pakistan; 4 Pediatric Oncology Department, National Institute of Child Health, Karachi, Pakistan; 5 Department of Pediatrics, the Hospital for Sick Children, University of Toronto, Toronto, Canada; 6 Department of Pediatric Medicine, Division of Hematology Oncology, Sidra Medical and Research Center, Doha, Qatar Grant sponsor: Aga Khan University Research Council Conflict of interest: Nothing to declare.  Correspondence to: Zehra Fadoo, Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, PO Box No. 3500, Karachi, Pakistan. E-mail: zehra.fadoo@aku.edu Received 26 June 2014; Accepted 13 April 2015  C 2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25583 Published online 15 May 2015 in Wiley Online Library (wileyonlinelibrary.com).