Outcomes of Low and Middle Income Children with Relapsed Acute Lymphoblastic Leukemia: Single-Center Experience
Öz
Abstract
Aim: Despite numerous advances in treating acute lymphoblastic leukemia (ALL) in children, relapse continues to be the leading cause of mortality. This study aimed to analyze the data of patient’s characteristics, and outcomes of children with relapsed ALL.
Material and Method: We retrospectively analyzed the records of patients aged 1–18 years diagnosed with relapsed ALL between January 2004 and December 2018.
Results: 452 ALL patients followed up in the study period and 55 patients relapsed. The relap-se rate was 12.1%. Thirty-four (61.8%) of the relapsed patients were male. The median age was seven years (1–17 years). Forty-six patients (83.6%) had precursor B-cell ALL and nine pati-ents (16.3%) had T-cell ALL. The site of relapse was bone marrow in 41 patients (74.5%), and extramedullary (central nervous system, testis, or soft tissue) in 11 patients (20%). The mean duration from the initial diagnosis to relapse was 32 months ( min-max: 4 -108 months, SD±21.2) and 20 months (min-max: 7-38 months, SD± 11.1) in patients with B- cell ALL and T- cell ALL respectively. The median follow-up time was 39.8 months (min-max: 3–198 months, SD±44.5) from the initial diagnosis. Thirty-seven patients (67.3%) died. The 5-year overall survival rate was 41.6%. Recurrent relapse and progressive disease were the most com-mon causes of death. The mortality rate was significantly associated with the immunophenotype, treatment response on days 8, 15, and 33 of initial diagnosis, the risk group at initial diagnosis, the site of relapse, and hematopoietic stem cell transplantation (p<0.05). Immunophenotype and the site of relapse were the independent variables associated with mortality.
Conclusion: Relapse affects a significant portion of patients with ALL. Survival rates are still poor in patients with relapsed ALL. Also, our findings that T-cell immunophenotype and the site of relapse (isolated bone marrow relapse) were independent risk factors for mortality sug-gest that more specialized treatment options are needed for patients with T-ALL and bone mar-row relapse.
Anahtar Kelimeler
Destekleyen Kurum
No Funding
Kaynakça
- 1.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. Oncol Lett. 2018;16(3):2929-2934.
- 2.Tuong PN, Kiem Hao T, Kim Hoa NT. Relapsed Childhood Acute Lymphoblastic Leukemia: A Single-Institution Experience. Cureus. 2020;12(7):e9238.
- 3. Oskarsson T, Söderhäll S, Arvidson J, Forestier E, Montgomery S, Bottai M, Lausen B, Carlsen N, Hellebostad M, Lähteenmäki P, Saarinen-Pihkala UM, Jónsson ÓG, Heyman M; Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL relapse working group. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment, and outcome. Haematologica. 2016;101(1):68-76 (1).
- 4. Pierro J, Hogan LE, Bhatla T, Carroll WL. New targeted therapies for relapsed pediatric acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2017;17(8):725-736
- 5. Locatelli F, Schrappe M, Bernardo ME and Rutella S: How I treat relapsed childhood acute lymphoblastic leukemia. Blood 120: 2807-2816, 2012.
- 6. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016;11(5):385-94.
- 7. Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-50.(14).
- 8. REZ BFM (Henze G, v Stackelberg A, Eckert C. ALL-REZ BFM--the consecutive trials for children with relapsed acute lymphoblastic leukemia. Klin Padiatr. 2013;225 Suppl 1:S73-S78.
- 9. Jaime-Pérez JC, Pinzón-Uresti MA, Jiménez-Castillo RA, Colunga-Pedraza JE, González-Llano Ó, Gómez-Almaguer D. Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor. Hematology. 2018;23(1):1-9.
- 10. Hazar V, Karasu GT, Uygun V, Akcan M, Küpesiz A, Yesilipek A. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience. J Pediatr Hematol Oncol. 2010;32(8):e317-e322.
- 11. Güneş AM, Oren H, Baytan B, et al. The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol. Ann Hematol. 2014;93(10):1677-1684.
- 12. Einsiedel HG, von Stackelberg A, Hartmann R, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87 [published correction appears in J Clin Oncol. 2008 May 1;26(13):2238]. J Clin Oncol. 2005;23(31):7942-7950.
- 13. Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, Ebell W, Escherich G, Schrappe M, Klingebiel T, Fengler R, Henze G, von Stackelberg A.Long-term outcome in children with relapsed acute lymphoblastic leukemia aftertime-point and site-of-relapse stratification and intensified short-coursemultidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010,10;28(14):2339-47.(6)
- 14. Ceppi F, Duval M, Leclerc JM, Laverdiere C, Delva YL, Cellot S, Teira P, Bittencourt H. Improvement of the Outcome of Relapsed or Refractory Acute Lymphoblastic Leukemia in Children Using a Risk-Based Treatment Strategy. PLoS One. 2016, 15;11(9):e0160310.
- 15. Freyer DR, Devidas M, La M, Carroll WL, Gaynon PS, Hunger SP, Seibel NL. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group. Blood. 2011,17;117(11):3010-5.
- 16.Teachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 2019;20(3):e142-e154.
- 17.Chessells JM, Veys P, Kempski H, Henley P, Leiper A, Webb D, Hann IM. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. Br J Haematol. 2003;123(3):396-405.
- 18. Forestier E, Johansson B, Gustafsson G, Borgström G, Kerndrup G, Johannsson J, Heim S. Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods. For the Nordic Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic Study Group. Br J Haematol. 2000;110(1):147-53.
- 19.Roberts KG, Reshmi SC, Harvey RC, Chen IM, Patel K, Stonerock E, Jenkins H, Dai Y, Valentine M, Gu Z, Zhao Y, Zhang J, Payne-Turner D, Devidas M, Heerema NA, Carroll AJ, Raetz EA, Borowitz MJ, Wood BL, Mattano LA Jr, Maloney KW, Carroll WL, Loh ML, Willman CL, Gastier-Foster JM, Mullighan CG, Hunger SP. Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group. Blood. 2018, 23;132(8):815-824.
- 20.Pui CH, Roberts KG, Yang JJ, Mullighan CG. Philadelphia Chromosome-like Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2017 Aug;17(8):464-470.
- 21.Heatley SL, Sadras T, Kok CH, Nievergall E, Quek K, Dang P, McClure B, Venn N, Moore S, Suttle J, Law T, Ng A, Muskovic W, Norris MD, Revesz T, Osborn M, Moore AS, Suppiah R, Fraser C, Alvaro F, Hughes TP, Mullighan CG, Marshall GM, Pozza LD, Yeung DT, Sutton R, White DL. High prevalence of relapse in children with Philadelphia-like acute lymphoblastic leukemia despite risk-adapted treatment. Haematologica. 2017;102(12):e490-e493.
- 22.Hunger SP, Raetz EA. How I treat relapsed acute lymphoblastic leukemia in the pediatric population. Blood. 2020, 15;136(16):1803-1812.
- 23. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14(6):e205-17.
- 24. Gaynon PS, Harris RE, Altman AJ, Bostrom BC, Breneman JC, Hawks R, Steele D,Zipf T, Stram DO, Villaluna D, Trigg ME. Bone marrow transplantation versusprolonged intensive chemotherapy for children with acute lymphoblastic leukemiaand an initial relapse within 12 months of the completion of primary therapy: Children's Oncology Group study CCG-1941. J Clin Oncol. 2006,1;24(19):3150-6.
- 25. Dopfer R, Henze G, Bender-Götze C, Ebell W, Ehninger G, Friedrich W, Gadner H,Klingebiel T, Peters C, Riehm H, et al. Allogeneic bone marrow transplantationfor childhood acute lymphoblastic leukemia in second remission after intensiveprimary and relapse therapy according to the BFM- and CoALL-protocols: results ofthe German Cooperative Study. Blood. 1991,15;78(10):2780-4
- 26. Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-Acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2020, 30. pii: haematol.2019.237230.
Nüks Eden Akut Lenfoblastik Lösemili Düşük ve Orta Gelirli Çocukların Sonuçları: Tek Merkez Deneyimi
Öz
Öz
Amaç: Çocuklarda akut lenfoblastik löseminin (ALL) tedavisindeki sayısız ilerlemeye rağmen, nüks mortalitenin önde gelen nedeni olmaya devam etmektedir. Bu çalışma ile, nüks eden ALL'li hasta özelliklerine ilişkin verileri ve çocukların sonuçlarını analiz etmeyi amaçlanmıştır.
Gereç ve Yöntem: Ocak 2004 ile Aralık 2018 tarihleri arasında nüks ALL tanısı alan 1-18 yaş arası hastaların kayıtlarını retrospektif olarak inceledik.
Bulgular: Çalışma döneminde 452 ALL hastası izlendi ve 55 hasta nüks ettiği görüldü. Nüks oranı %12.1 idi. Bu hastaların 34'ü (%61,8) erkekti. Medyan yaş 7 yıl (min-maks:1-17 yaş) idi. Kırk altı hastada (%83,6) öncül B-hücreli ALL ve dokuz hastada (%16,3) T-hücreli ALL vardı. Kırk bir hastada (%74,5) nüks yeri kemik iliği, 11 hastada (%20) ekstramedüller (merkezi sinir sistemi, testis veya yumuşak doku) idi. İlk tanıdan nükse kadar geçen ortalama süre B hücreli ALL'li hastalarda 32 ay (min-maks: 4 -108 ay, SD±21,2) ve T-hücre ALL’ de 20 ay (min-maks: 7-38 ay, SD± 11,1) idi. Tanıdan itibaren ortanca takip süresi 39,8 aydı (min-maks: 3–198 ay, SD±44,5). Otuz yedi hasta (%67,3) öldü. 5 yıllık genel sağkalım oranı %41.6 idi. Tekrarlayan nüks ve ilerleyici hastalık en yaygın ölüm nedenleriydi. Mortalite oranı, immünofenotip, ilk tanı-nın 8., 15. ve 33. günlerinde tedaviye yanıt, ilk tanı anındaki risk grubu, nüks bölgesi ve hematopoietik kök hücre nakli ile anlamlı şekilde ilişkiliydi (p<0.05). İmmünofenotip ve nüks bölge-si, mortalite ile ilişkili bağımsız değişkenlerdi.
Sonuç: Nüks, ALL hastalarının önemli bir bölümünü etkiler. Tekrarlayan ALL'li hastalarda hayatta kalma oranları hala düşüktür. Ayrıca, T-hücre immünofenotipi ve nüks bölgesi (izole kemik iliği nüksü) mortalite için bağımsız risk faktörleri olduğuna dair bulgularımız, T-ALL ve kemik iliği nüksü olan hastalar için daha özel tedavi seçeneklerine ihtiyaç olduğunu düşündürmektedir.
Anahtar Kelimeler
Kaynakça
- 1.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. Oncol Lett. 2018;16(3):2929-2934.
- 2.Tuong PN, Kiem Hao T, Kim Hoa NT. Relapsed Childhood Acute Lymphoblastic Leukemia: A Single-Institution Experience. Cureus. 2020;12(7):e9238.
- 3. Oskarsson T, Söderhäll S, Arvidson J, Forestier E, Montgomery S, Bottai M, Lausen B, Carlsen N, Hellebostad M, Lähteenmäki P, Saarinen-Pihkala UM, Jónsson ÓG, Heyman M; Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL relapse working group. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment, and outcome. Haematologica. 2016;101(1):68-76 (1).
- 4. Pierro J, Hogan LE, Bhatla T, Carroll WL. New targeted therapies for relapsed pediatric acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2017;17(8):725-736
- 5. Locatelli F, Schrappe M, Bernardo ME and Rutella S: How I treat relapsed childhood acute lymphoblastic leukemia. Blood 120: 2807-2816, 2012.
- 6. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016;11(5):385-94.
- 7. Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-50.(14).
- 8. REZ BFM (Henze G, v Stackelberg A, Eckert C. ALL-REZ BFM--the consecutive trials for children with relapsed acute lymphoblastic leukemia. Klin Padiatr. 2013;225 Suppl 1:S73-S78.
- 9. Jaime-Pérez JC, Pinzón-Uresti MA, Jiménez-Castillo RA, Colunga-Pedraza JE, González-Llano Ó, Gómez-Almaguer D. Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor. Hematology. 2018;23(1):1-9.
- 10. Hazar V, Karasu GT, Uygun V, Akcan M, Küpesiz A, Yesilipek A. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience. J Pediatr Hematol Oncol. 2010;32(8):e317-e322.
- 11. Güneş AM, Oren H, Baytan B, et al. The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol. Ann Hematol. 2014;93(10):1677-1684.
- 12. Einsiedel HG, von Stackelberg A, Hartmann R, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87 [published correction appears in J Clin Oncol. 2008 May 1;26(13):2238]. J Clin Oncol. 2005;23(31):7942-7950.
- 13. Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, Ebell W, Escherich G, Schrappe M, Klingebiel T, Fengler R, Henze G, von Stackelberg A.Long-term outcome in children with relapsed acute lymphoblastic leukemia aftertime-point and site-of-relapse stratification and intensified short-coursemultidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010,10;28(14):2339-47.(6)
- 14. Ceppi F, Duval M, Leclerc JM, Laverdiere C, Delva YL, Cellot S, Teira P, Bittencourt H. Improvement of the Outcome of Relapsed or Refractory Acute Lymphoblastic Leukemia in Children Using a Risk-Based Treatment Strategy. PLoS One. 2016, 15;11(9):e0160310.
- 15. Freyer DR, Devidas M, La M, Carroll WL, Gaynon PS, Hunger SP, Seibel NL. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group. Blood. 2011,17;117(11):3010-5.
- 16.Teachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 2019;20(3):e142-e154.
- 17.Chessells JM, Veys P, Kempski H, Henley P, Leiper A, Webb D, Hann IM. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. Br J Haematol. 2003;123(3):396-405.
- 18. Forestier E, Johansson B, Gustafsson G, Borgström G, Kerndrup G, Johannsson J, Heim S. Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods. For the Nordic Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic Study Group. Br J Haematol. 2000;110(1):147-53.
- 19.Roberts KG, Reshmi SC, Harvey RC, Chen IM, Patel K, Stonerock E, Jenkins H, Dai Y, Valentine M, Gu Z, Zhao Y, Zhang J, Payne-Turner D, Devidas M, Heerema NA, Carroll AJ, Raetz EA, Borowitz MJ, Wood BL, Mattano LA Jr, Maloney KW, Carroll WL, Loh ML, Willman CL, Gastier-Foster JM, Mullighan CG, Hunger SP. Genomic and outcome analyses of Ph-like ALL in NCI standard-risk patients: a report from the Children's Oncology Group. Blood. 2018, 23;132(8):815-824.
- 20.Pui CH, Roberts KG, Yang JJ, Mullighan CG. Philadelphia Chromosome-like Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2017 Aug;17(8):464-470.
- 21.Heatley SL, Sadras T, Kok CH, Nievergall E, Quek K, Dang P, McClure B, Venn N, Moore S, Suttle J, Law T, Ng A, Muskovic W, Norris MD, Revesz T, Osborn M, Moore AS, Suppiah R, Fraser C, Alvaro F, Hughes TP, Mullighan CG, Marshall GM, Pozza LD, Yeung DT, Sutton R, White DL. High prevalence of relapse in children with Philadelphia-like acute lymphoblastic leukemia despite risk-adapted treatment. Haematologica. 2017;102(12):e490-e493.
- 22.Hunger SP, Raetz EA. How I treat relapsed acute lymphoblastic leukemia in the pediatric population. Blood. 2020, 15;136(16):1803-1812.
- 23. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013;14(6):e205-17.
- 24. Gaynon PS, Harris RE, Altman AJ, Bostrom BC, Breneman JC, Hawks R, Steele D,Zipf T, Stram DO, Villaluna D, Trigg ME. Bone marrow transplantation versusprolonged intensive chemotherapy for children with acute lymphoblastic leukemiaand an initial relapse within 12 months of the completion of primary therapy: Children's Oncology Group study CCG-1941. J Clin Oncol. 2006,1;24(19):3150-6.
- 25. Dopfer R, Henze G, Bender-Götze C, Ebell W, Ehninger G, Friedrich W, Gadner H,Klingebiel T, Peters C, Riehm H, et al. Allogeneic bone marrow transplantationfor childhood acute lymphoblastic leukemia in second remission after intensiveprimary and relapse therapy according to the BFM- and CoALL-protocols: results ofthe German Cooperative Study. Blood. 1991,15;78(10):2780-4
- 26. Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-Acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2020, 30. pii: haematol.2019.237230.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Çocuk Hematolojisi ve Onkolojisi |
| Bölüm | Orjinal Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Eylül 2023 |
| Kabul Tarihi | 16 Eylül 2023 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 13 Sayı: 5 |
