Acute megakaryoblastic leukemia medical therapy

Jump to navigation Jump to search

Acute megakaryoblastic leukemia Microchapters

Home

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Acute megakaryoblastic leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Acute megakaryoblastic leukemia medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Acute megakaryoblastic leukemia medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Acute megakaryoblastic leukemia medical therapy

CDC on Acute megakaryoblastic leukemia medical therapy

Acute megakaryoblastic leukemia medical therapy in the news

Blogs on Acute megakaryoblastic leukemia medical therapy

Directions to Hospitals Treating Acute megakaryoblastic leukemia

Risk calculators and risk factors for Acute megakaryoblastic leukemia medical therapy

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.

Template:WH Template:WS