Outcome of Intensive Therapy for Children with Relapsed Acute Myeloid Leukemia: A Single Institution Korean Study
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution. Materials and methods: The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Results: Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free. Conclusion: Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.
Abstract
Purpose: Approximately 30%-40% of pediatric acute myeloid leukemia (AML) patients relapse. In this study, we analyzed the outcome and prognostic factors of relapsed AML patients who had previously received first-line therapy at our institution. Materials and methods: The study group consisted of 50 patients who had been diagnosed with AML from April 2009 to December 2018, and then showed first relapse. Thirty-two of the patients (64%) had previously received allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Results: Forty-five of the patients (90%) received intensive chemotherapy upon diagnosis of relapse, and 76% (34/45) of these patients achieved a second CR. Estimated 5-year overall survival for these 45 patients was 44.9%±7.6%. Time from diagnosis to relapse, extramedullary involvement (EMI) at diagnosis, core binding factor AML, and complex karyotype were significant prognostic factors; in multivariate study, both time from diagnosis to relapse and EMI at diagnosis proved significant. There was no difference in 5-year disease-free survival between patients previously treated with chemotherapy only and those who received HSCT in first CR (52.4%±14.9% vs. 52.6%±11.5%). Of the 19 patients who achieved second CR after previous allogeneic HSCT in first CR and subsequent relapse, 11 were treated with chemotherapy only, and seven survive disease-free. Conclusion: Intensive therapy allowed for long-term survival in 40%-50% of patients, and 50% of patients who achieved second CR, regardless of prior treatment modalities in first CR. Intensive treatment may allow for salvage of a significant portion of patients with relapsed pediatric AML.
참고문헌 (23)
- Rasche M, "Successes and challenges in the treatment of pediatric acute myeloid leukemia : a retrospective analysis of the AML-BFM trials from 1987 to 2012", Leukemia, 32, pp.2167~2177 (2018)
- Webb DK, "Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party", Leukemia, 13, pp.25~31 (1999)
- Rubnitz JE, "Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia", Cancer, 109, pp.157~163 (2007)
- Sander A, "Consequent and intensified relapse therapy improved survival in pediatric AML : results of relapse treatment in 379 patients of three consecutive AML-BFM trials", Leukemia, 24, pp.1422~1428 (2010)
- Karlsson L, "Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia", Br J Haematol, 178, pp.592~602 (2017)
- Moritake H, "The outcomes of relapsed acute myeloid leukemia in children : results from the Japanese Pediatric Leukemia", Lymphoma Study Group AML-05R study, 2021, pp.68, e28736~
- Rasche M, "Survival following relapse in children with acute myeloid leukemia : a report from AML-BFM and COG", Cancers(Basel), 13, pp.2336~ (2021)
- Kaspers GJ, "Improved outcome in pediatric relapsed acute myeloid leukemia : results of a randomized trial on liposomal daunorubicin by the International BFM Study Group", J Clin Oncol, 31, pp.599~607 (2013)
- Creutzig U, "The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia : results of the international study Relapsed AML 2001", 01, 2014, pp.99, 1472~1478
- Lee JW, "Treatment of children with acute myeloid leukaemia who relapsed after allogeneic haematopoietic stem cell transplantation", Br J Haematol, 160, pp.80~86 (2013)
- Lee JW, "Prognostic role of postinduction minimal residual disease and myeloid sarcoma type extramedullary involvement in pediatric RUNX1-RUNX1T1(+)acute myeloid leukemia", J Pediatr Hematol Oncol, 42, pp.e132~e139 (2020)
- Ravandi F, "Phase I", II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia, 2010, pp.28, 1856~1862
- Gorman MF, "Outcome for children treated for relapsed or refractory acute myelogenous leukemia(rAML) : a Therapeutic Advances in Childhood Leukemia(TACL)Consortium study", Pediatr Blood Cancer, 55, pp.421~429 (2010)
- Fleischhack G, "IDA-FLAG(idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation : experiences of a phase II trial", Br J Haematol, 102, pp.647~655 (1998)
- Niktoreh N, "Gemtuzumab ozogamicin in children with relapsed or refractory acute myeloid leukemia : a report by Berlin-Frankfurt-Munster study group", Haematologica, 104, pp.120~127 (2019)
- Karol SE, "Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia : a phase 1, dose-escalation study", Lancet Oncol, 21, pp.551~560 (2020)
- Stove HK, "Extramedullary leukemia in children with acute myeloid leukemia : a population-based cohort study from the Nordic Society of Pediatric Hematology and Oncology(NOPHO)", Pediatr Blood Cancer, 64, pp.e26520~ (2017)
- Sakaguchi H, "Effect of extramedullary disease on alloge-neic hematopoietic cell transplantation for pediatric acute myeloid leukemia : a nationwide retrospective study", Bone Marrow Transplant, 56, pp.1859~1865 (2021)
- Nakayama H, "Outcome of children with relapsed acute myeloid leukemia following initial therapy under the AML99 protocol", Int J Hematol, 100, pp.171~179 (2014)
- von NeuhoffC, "Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98", J Clin Oncol, 28, pp.2682~2689 (2010)
- Selim A, "Hematopoietic stem cell transplantation for children with acute myeloid leukemia in second remission : a report from the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children’s Haematology Oncology Group", Pediatr Blood Cancer, 66, pp.e27812~ (2019)
- Uden T, "Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia : a retrospective I-BFM analysis of 333 children", Br J Haematol, 189, pp.745~750 (2020)
- Yahng SA, "A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia", Biol Blood Marrow Transplant, 21, pp.119~129 (2015)