Acute megakaryoblastic leukemia medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Medical Therapy
- According to the AML-BFM (Berlin–Frankfurt–Münster) 98 and AML-BFM ((Berlin–Frankfurt–Münster) 93 clinical studies, intensive AML targeted chemotherapy in Down syndrome-associated AMKL results in high event-free survival rates versus non-Down syndrome patients. However, they are also prone to develop treatment-related toxicity at standard doses due to chemo sensitivity.[1]
The treatment is divided into induction therapy and consolidation therapy.
- Induction therapy — involves two cycles (four weeks apart ) of Ara-Cytarabine (Ara-C) at 100 mg/m2 /day continuous infusion for 7 days, vincristine at 0.7 mg/m2 on day 7, and pirarubicin at 25 mg/m2 by 60 min infusion on days 2, and 4 (AVC1).[2]
- Consolidation therapy — follows once complete remission is achieved with the following regimen; etoposide & high-dose Ara-C (EC), mitoxantrone and continuous-dose Ara-C (MC), and pirarubicin, vincristine, and continuous-dose Ara-C (AVC2).[3]
The doses are given below:[4]
MC regimen:
- Ara-C at 100 mg/m2 /day continuous infusion for 5 days and
- Mitoxantrone at 3.5 mg/m2 by 60 min infusion on days 2–4
EC regimen
- High-dose Ara-C 1 g/m2 every 12 hrs on days 1–5,
- Etoposide 66 mg/m2 by 2 h infusion on days 2–4), and
AVC2 regimen
- Ara-C at 100 mg/m2 /day on days 1–5,
- Pirarubicin 35 mg/m2 by 60 min infusion on day 2, and
- Vincristine at 0.7 mg/m2 on day 5
In relapsed state, re-induction with fludarabine and Ara-C combination or same AVC regimen can be utilized. Allogenic bone marrow transplant (Allo-BMT) from a suitable donor is justified if the patients achieved second complete remission. Currently, there is no recommended definitive therapy for non-Down syndrome with AMKL cohort. Novel therapeutic interventions are undertaken.[5]
- Some study groups proposed that non-Down syndrome with AMKL is a high-risk condition; therefore, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) during first complete remission is recommended to benefit the patients. In contrast, no benefit of Allo-HSCT is evident over chemotherapy without remission.[6]
- In AML-BFM 04 trial, patients were randomized to receive induction therapy with either (Ara-C), liposomal daunorubicin, and etoposide (ADxE) or Ara-C, idarubicin, and etoposide (AIE) regimen. Consolidation therapy with 2-chloro-2-deoxyadenosine (2-CDA) and Ara-C and idarubicin was preceded by second induction therapy with HAM (high-dose Ara-C, mitoxantrone, cytarabine i.th). However, no significant results were obtained regarding event-free survival (EFS) and overall survival (OS).[7]
References
- ↑ Creutzig, U; Reinhardt, D; Diekamp, S; Dworzak, M; Stary, J; Zimmermann, M (2005). "AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity". Leukemia. 19 (8): 1355–1360. doi:10.1038/sj.leu.2403814. ISSN 0887-6924.
- ↑ Taga, Takashi; Shimomura, Yasuto; Horikoshi, Yasuo; Ogawa, Atsushi; Itoh, Masaki; Okada, Masahiko; Ueyama, Junichi; Higa, Takeshi; Watanabe, Arata; Kanegane, Hirokazu; Iwai, Asayuki; Saiwakawa, Yutaka; Kogawa, Kazuhiro; Yamanaka, Junko; Tsurusawa, Masahito (2011). "Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study". Pediatric Blood & Cancer. 57 (1): 36–40. doi:10.1002/pbc.22943. ISSN 1545-5009.
- ↑ Taga, Takashi; Shimomura, Yasuto; Horikoshi, Yasuo; Ogawa, Atsushi; Itoh, Masaki; Okada, Masahiko; Ueyama, Junichi; Higa, Takeshi; Watanabe, Arata; Kanegane, Hirokazu; Iwai, Asayuki; Saiwakawa, Yutaka; Kogawa, Kazuhiro; Yamanaka, Junko; Tsurusawa, Masahito (2011). "Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study". Pediatric Blood & Cancer. 57 (1): 36–40. doi:10.1002/pbc.22943. ISSN 1545-5009.
- ↑ Taga, Takashi; Shimomura, Yasuto; Horikoshi, Yasuo; Ogawa, Atsushi; Itoh, Masaki; Okada, Masahiko; Ueyama, Junichi; Higa, Takeshi; Watanabe, Arata; Kanegane, Hirokazu; Iwai, Asayuki; Saiwakawa, Yutaka; Kogawa, Kazuhiro; Yamanaka, Junko; Tsurusawa, Masahito (2011). "Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study". Pediatric Blood & Cancer. 57 (1): 36–40. doi:10.1002/pbc.22943. ISSN 1545-5009.
- ↑ De Marchi, Federico; Araki, Marito; Komatsu, Norio (2019). "Molecular features, prognosis, and novel treatment options for pediatric acute megakaryoblastic leukemia". Expert Review of Hematology. 12 (5): 285–293. doi:10.1080/17474086.2019.1609351. ISSN 1747-4086.
- ↑ Athale, Uma H.; Razzouk, Bassem I.; Raimondi, Susana C.; Tong, Xin; Behm, Frederick G.; Head, David R.; Srivastava, Deo K.; Rubnitz, Jeffrey E.; Bowman, Laura; Pui, Ching-Hon; Ribeiro, Raul C. (2001). "Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience". Blood. 97 (12): 3727–3732. doi:10.1182/blood.V97.12.3727. ISSN 1528-0020.
- ↑ Schweitzer, Jana; Zimmermann, Martin; Rasche, Mareike; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Reinhardt, Dirk; Klusmann, Jan-Henning (2015). "Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial". Annals of Hematology. 94 (8): 1327–1336. doi:10.1007/s00277-015-2383-2. ISSN 0939-5555.