Pediatr Blood Cancer 2016;63:458–464 Evaluation and Outcome of Central Nervous System Involvement in Pediatric Acute Lymphoblastic Leukemia in Dar es Salaam, Tanzania Cheryl Cohler, MD, 1 Shakilu Jumanne, MD, 2 Jane Kaijage, PC AMD, 2 Steven G. DuBois, MD, 1 Patricia Scanlan, MD, 2 and Katherine K. Matthay, MD 1* Background. Outcomes for acute lymphoblastic leukemia (ALL) in low-income countries lag far behind high-income countries (HIC). We explored the impact of central nervous system (CNS) involve- ment on outcome of pediatric patients with ALL in Tanzania. Procedure. Comprehensive chart review was performed to character- ize CNS involvement, treatment, and outcomes of pediatric patients with ALL at Muhimbili National Hospital in Dar es Salaam, Tan- zania between January 1, 2011 and December 31, 2013. Results. One hundred fifty-six patients with confirmed ALL had accessible data, and 128 initiated therapy. Sixteen percent of 156 patients had a documented cerebral spinal fluid analysis by cytospin. Seventy pa- tients (45%) had a documented lumbar puncture with intrathecal (IT) therapy within 1 week of diagnosis. Thirteen patients presented with CNS involvement at diagnosis based on cytospin and/or unequivo- cal symptoms. Twenty-one patients (16%) experienced CNS relapse, three of whom had CNS disease at diagnosis. Median event-free sur- vival (EFS) for all patients was 7.9 months and estimated EFS at 24 months was 31%. For the patients with CNS involvement at diag- nosis, the estimated EFS at 24 months was 45%. Only three of 21 patients with CNS relapse were still alive with a median follow up of 3 months. Conclusions. The rate of CNS disease in patients with ALL in Dar es Salaam at diagnosis and relapse was higher than that re- ported in HIC, and overall survival was lower. Improving outcomes will require further advances including consistent CNS prophylaxis and may include targeting high-risk patients with additional IT treat- ments. Pediatr Blood Cancer 2016;63:458–464. C  2015 Wiley Pe- riodicals, Inc. Key words: acute lymphoblastic leukemia; central nervous system; low-income country INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. The central nervous system (CNS) can provide a sanctuary site for leukemic cells due to a blood brain barrier, which makes it diicult for systemic chemotherapy and immune cells to penetrate. Therefore, CNS- directed therapy is standard to prevent relapse of sequestered leukemic cells. Cranial radiation, once standard CNS prophy- laxis, has been replaced by intrathecal (IT) chemotherapy to re- duce neurotoxic side efects.[1–3] The overall survival of ALL in high-income countries (HICs) using IT CNS prophylaxis is greater than 80%, and the CNS relapse rate is <3%.[1,2] Mortality for childhood ALL is inversely associated with na- tional income, so while there have been improvements in sur- vival in low- and middle-income countries (LMIC) over the past decades, survival rarely exceeds 35%.[4,5] Treatment protocols in LMIC are based on outcomes of clinical trials done in HICs, so local research is needed to adjust for limited resources.[6,7] For example, a cancer center in India that followed international rec- ommendations to omit prophylactic cranial radiation had sig- niicantly higher CNS relapse rates in pediatric patients with ALL than their Western counterparts.[8] Whether this rate was due to a greater incidence of high-risk disease, less aggressive chemotherapy, or a diferent biology of malignant cells is un- known.[8] These factors raise the question of the optimal CNS leukemia prophylaxis and treatment in LMIC. In Tanzania, a low-income country (LIC) in East Africa, there is one pediatric cancer center in Dar es Salaam. There is one published study of childhood leukemia in this center, which cites a lack of diagnostic procedures for CNS disease, causing delay in diagnosis at presentation or relapse.[9] Over the past 5 years, a process of continued improvement using protocolized therapy for ALL and staf education has been implemented. The aim of our retrospective analysis of CNS leukemia in Dar es Salaam is to report more recent rates of CNS disease detection and presentation, prophylaxis, treatment, and association with relapse and outcomes in order to provide information on cur- rent resources and necessary advances. METHODS We performed chart review for patients with an ALL diag- nosis hospitalized at the Muhimbili National Hospital (MNH) between January 1, 2011 and December 31, 2013 with follow-up through May 1, 2014. The UCSF institutional review board and the MNH ailiate Muhimbili University of Health and Allied Sciences ethics committee approved this retrospective review. Additional Supporting Information may be found in the online ver- sion of this article. Abbreviations: ALL, acute lymphoblastic leukemia; BM, bone marrow; CI, conidence interval; CNS, central nervous system; CSF, cerebral spinal luid; EFS, event-free survival; HICs, high-income countries; IT, intrathecal; IV, intravenous; LICs, low-income coun- tries; LMIC, low- and middle-income countries; LP, lumbar punc- ture; MNH, Muhimbili National Hospital; MTX, methotrexate; WBC, white blood cell 1 Department of Pediatrics, UCSF School of Medicine and UCSF Beniof Children’s Hospital, University of California, San Fran- cisco, California; 2 Department of Pediatrics, Muhimbili National Hospital, Dar es Salaam, Tanzania Grant sponsor: Mildred V. Strouss Chair; Grant sponsor: Conner fund; Grant sponsor: RAPtr Global Health Fund. Conlict of interest: Nothing to declare. ∗ Correspondence to: Katherine K. Matthay, Department of Pedi- atrics, UCSF School of Medicine, and UCSF Beniof Children’s Hospital, University of California, 550 16th Ave, 4th Floor, Box 0434, San Francisco, CA 94143. E-mail: Kate.Matthay@ucsf.edu Received 11 August 2015; Accepted 5 October 2015 C  2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25829 Published online 3 November 2015 in Wiley Online Library (wileyonlinelibrary.com).