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Retrospective Study on Very Early Relapse of Childhood Acute Lymphoblastic Leukemia at a Reference Centre in Indonesia

  • Nur Melani Sari ,
  • Namira Assyfa Nurazizah ,
  • Ronny Lesmana ,
  • Nur Suryawan ,
  • Susi Susanah ,

Abstract

Introduction: The cure rate of Acute Lymphoblastic Leukemia (ALL) in low and middle-income countries is still low. Many factors contribute to relapses event, thus leading to failure of the treatment outcome. However, there are limited studies regarding the relapse of childhood cancer in Indonesia. This study determined demography, clinical, and characteristic laboratory differentiation between relapse and non-relapse in the bone marrow childhood ALL group.

Methods: This was a retrospective descriptive study in children newly diagnosed with ALL ages 0-18 who completed the induction phase using the 2013 treatment protocol during the 2018 period in Pediatrics Hematology-Oncology Unit at a reference center hospital in Indonesia. Of 78 data collected from the Indonesian Pediatric Cancer Registry (IP-CAR) and Hospital Information System after excluding abandoned treatment or death during treatment, only 35 patients completed the overall therapy. We evaluated bone marrow relapse and classified it into 'very early' relapse that occurs at least 18 months from diagnosis, 'early' relapse between 18 and 36 months, and more than 36 months is called 'late' relapse. Chi-square test was used to elaborate association between relapse and sex, leukocyte count, morphological classification, risk stratification, nutritional status. Kruskal Wallis tests were used to elaborate on the association between relapse, age, and induction duration. P value<0.05 was considered statistically significant.

Results: Among 35 patients in this study, seven patients experienced bone marrow relapse. Relapses were dominant in four male patients, four patients aged from 1-10 years old, six patients with leukocytes count below 50.000/mm3, six normal nutritional status patients, and six patients classified as L2 patients. All relapse events occurred in a very early stage. Four patients are classified as standard risk, and three patients are high risk. There were no significant differences among characteristics of the relapse and non-relapse groups.

Conclusions: The observed relapse onset is less than 18 months from diagnosis (very early relapse) during maintenance treatment. However, we found no significant demography, clinical, and laboratory differentiation between relapse and non-relapse groups.

References

  1. Situasi Penyakit Kanker: Prevalensi Kanker di Indonesia. 2015.
  2. Sari N, Reniarti L, Suryawan N, Susanah S, Wahyudi K. Burden of Pediatric Cancer Treatment : Results of Online Pediatric Cancer Registry Prototype 1 at A Third Referral Hospital in Indonesia. 2017;4:465.
  3. Sitaresmi MN, Mostert S, Schook RM, Staryo, Veerman AJP. Treatment refusal and abandonment in childhood acute lymphoblastic leukemia in Indonesia: An analysis of causes and consequences. Psychooncology. 2010;19:361.
  4. Sitaresmi MN, Mostert S, Purwanto I, Gundy CM, Sutaryo, Veerman AJP. Chemotherapy-related side effects in childhood acute lymphoblastic leukemia in Indonesia: Parental perceptions. J Pediatr Oncol Nurs. 2009;26:198-9.
  5. Ceppi F, Cazzaniga G, Colombini A, Biondi A, Conter V. Risk factors for relapse in childhood acute lymphoblastic leukemia: prediction and prevention. Expert Rev. Hematol. 2014;1-14.
  6. Schmiegelow K, Heyman M, Gustafsson G, Lausen B, Wesenberg F, Kristinsson J, et al. The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. Leukemia. 2010;24:715-720.
  7. Oskarsson T, Söderhäll S, Arvidson J, Forestier E, Montgomery S, Bottai M, et al. Relapsed Childhood Acute Lymphoblastic Leukemia In The Nordic Countries: Prognostic Factors, Treatment And Outcome. Haematologica. 2016;101(1):68-76.
  8. Indonesia UKKUH-OIDA. Protokol pengobatan leukemia limfoblastik akut anak 2013 (Indonesian Childhood ALL - 2013 Protocol) Indonesia. 2013.
  9. Hogan LE, Meyer JA, Yang J, Wang J, Wong N, Yang W, et al. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood. 2011;118:5218-5226.
  10. Siddiqui EU, Kazi SG, Habib MI, Khan KMA, Zia N. Pattern of relapse in paediatric acute lymphoblastic leukaemia in a tertiary care unit. JPMA. 2016;66:961.
  11. Schmiegelow K, Forestier E, Hellebostad M. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia. Leukemia. 2010;24:345-354.
  12. Hunger SP, Lu X, Devidas M. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012;30:1663-1669.
  13. Stary J, Zimmermann M, Campbell M. Intensive Chemotherapy for Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Intercontinental Trial ALL IC-BFM 2002. J Clin Oncol. 2014;32:174-184.
  14. Moricke A, Zimmermann M, Reiter A. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010;24:265-284.
  15. Escherich G, Horstmann MA, Zimmermann M, Janka-Schaub GE. Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97. Leukemia. 2009;24:298-308.
  16. Hernández EJ, Reyes EZJ, Galindo JA, Jimenez XG, Garcia HMT, Gonzales MTD. Survival of Mexican Children with Acute Lymphoblastic Leukemia under Treatment with the Protocol from the Dana-Faber Cancer Institute 00-01. BioMed Research International. 2014;10:1-9.
  17. Mushtaq N, Fadoo Z, Naqvi A. Childhood acute lymphoblastic leukaemia: experience from a single tertiary care facility of Pakistan. J Pak Med Assoc. 2013;63:404-1399.
  18. Jaime-Pérez JC, Jiménez-Castillo RA, Pinzón-Uresti MA, Cantú-Rodríguez OG, Herrera-Garza JL, Marfil-Rivera LJ, et al. Real-world outcomes of treatment for acute lymphoblastic leukemia during adolescence in a financially restricted environment: results at a single center in Latin America. Pediatr Blood Cancer. 2017:64.
  19. Pui CH, Yang JJ, Bhakta N, Galindo CR. Global Efforts Toward The Cure of Childhood Acute Lymphoblastic Leukemia. Lancet Child Adolesc Health. 2018;2:440–454.
  20. Kakaje A, Alhalabi MM, Ghareeb A, Karam B, Mansour B, Zhara B, et al. Rates and Trends of Childhood Acute Lymphoblastic Leukaemia: an Epidemiology Study. Scientific Reports Nature. 2020;10:6756.
  21. Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. British Journal of Haematology. 2013.
  22. Widiasksara IM., Permono B, Ratmita M. Luaran Pengobatan Fase Induksi Pasien Leukemia Limfoblastik Akut. Sari Pediatri. 2010;12:128–134.
  23. Möricke A, Zimmermann M, Reiter A, Gadner H, Odenwald E, Harbott J, et al. Prognostic Impact of Age in Children and Adolescents with Acute Lymphoblastic Leukemia: Data from the Trials ALL-BFM 86, 90, and 95. Klin Pädiatr. 2005;217:310–320.
  24. Mochtar Y, Ridha NR, Daud D. 2015. Age as a Risk Factor of Relapse Occurrence in Acute Lymphoblastic Leukemia-L1 in Children. American Journal of Clinical Experimental Medicine. 2015;3:124–127.
  25. Meidiana B. Factor analyses of genesis relapse in children with leukemia. Jakarta: RS Cipto Mangunkusomo. 2012.
  26. Rahma, Ridha NR, Daud D. Correlation Sex and Relapse of Childhood Acute Lymphoblastic Leukemia-L1 (All-L1). JST Kesehatan. 2016;6:76-82.
  27. Vaitkeviciene G, Heyman M, Jonsson OG, Lausen B, Saari AH, Stenmarker M, et al. Early morbidity and mortality in childhood acute lymphoblastic leukemia with very high white blood cell count. Leukemia. 2013;27:2259–2262.
  28. Moricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dordelmann M et al. Risk-adjusted therapy of acute lymphobastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008;111:4477–4489.
  29. Vaitkeviciene G, Forestier E, Hellebostad M, Heyman M, Jonsson OG, Lahteenmaki PM et al. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: biological background and prognostic impact. Results from the NOPHO ALL-92 and ALL-2000 studies. Eur J Haematol. 2011;86:38–46.
  30. Athifah A, Hidayati SN, Sulistiawati. Correlative Study Between Nutritional Status and Remission Outcome in Childhood Acute Lymphoblastic Leukemia in Dr. Soetomo General Hospital Surabaya. Biomolecular and Health Science Journal. 2019;02:27-30
  31. Zhang X, Wu H, Fan H, Su B, Zhang G, Dong L. Clinical characteristics and prognosis of pediatric patients with B cell acute lymphoblastic leukemia relapse. Oncology Letters. 2018;16:2929-2934.
  32. Ansari S, Sabzechian M, Kiumarsi A, Sabzechian M, Rostami T, Rouhani F. Suppression of Adrenal Axis Function after High-dose Steroid Therapy for Childhood Acute Lymphoblastic Leukemia in Iran. International Journal of Contemporary Pediatrics. 2014;1:164-167.
  33. Bhatia S, Landier W, Hageman L, Chen Y, Kim H, Sun CL, et al. Systemic Exposure to Thiopurine s and Risk of Relapse in Children With Acute Lymphoblastic Leukemia A Children's Oncology Group Study. JAMA Oncol. 2015;1:287-295.
  34. Oliveria BM, Viana MB, Zani CL, Romanha AJ. Clinical and laboratory evaluation of compliance in acute lymphoblastic leukaemia. Arch Dis Child. 2004; 89:785–788.
  35. Hayder S, Björk O, Nilsson B. Relapse Factors During Maintenance Therapy of Acute Lymphoblastic Leukemia in Children. Pediatric Hematology and Oncology. 2009;9:21-27.

How to Cite

Sari, N. M., Nurazizah, N. A., Lesmana, R., Suryawan, N., & Susanah, S. (2022). Retrospective Study on Very Early Relapse of Childhood Acute Lymphoblastic Leukemia at a Reference Centre in Indonesia. Bali Medical Journal, 11(1), 44–49. https://doi.org/10.15562/bmj.v11i1.2495

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