Acute megakaryoblastic leukemia medical therapy: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 2: | Line 2: | ||
{{Acute megakaryoblastic leukemia}} | {{Acute megakaryoblastic leukemia}} | ||
* 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.<ref name="CreutzigReinhardt2005">{{cite journal|last1=Creutzig|first1=U|last2=Reinhardt|first2=D|last3=Diekamp|first3=S|last4=Dworzak|first4=M|last5=Stary|first5=J|last6=Zimmermann|first6=M|title=AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity|journal=Leukemia|volume=19|issue=8|year=2005|pages=1355–1360|issn=0887-6924|doi=10.1038/sj.leu.2403814}}</ref> | *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.<ref name="CreutzigReinhardt2005">{{cite journal|last1=Creutzig|first1=U|last2=Reinhardt|first2=D|last3=Diekamp|first3=S|last4=Dworzak|first4=M|last5=Stary|first5=J|last6=Zimmermann|first6=M|title=AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity|journal=Leukemia|volume=19|issue=8|year=2005|pages=1355–1360|issn=0887-6924|doi=10.1038/sj.leu.2403814}}</ref> | ||
The treatment is divided into induction therapy and consolidation therapy. | 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).<ref name="TagaShimomura2011">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | *'''Induction therapy''' — involves two cycles (four weeks apart ) of [[Cytarabine|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).<ref name="TagaShimomura2011">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | ||
* '''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).<ref name="TagaShimomura20112">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | *'''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).<ref name="TagaShimomura20112">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | ||
The doses are given below:<ref name="TagaShimomura20113">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | The doses are given below:<ref name="TagaShimomura20113">{{cite journal|last1=Taga|first1=Takashi|last2=Shimomura|first2=Yasuto|last3=Horikoshi|first3=Yasuo|last4=Ogawa|first4=Atsushi|last5=Itoh|first5=Masaki|last6=Okada|first6=Masahiko|last7=Ueyama|first7=Junichi|last8=Higa|first8=Takeshi|last9=Watanabe|first9=Arata|last10=Kanegane|first10=Hirokazu|last11=Iwai|first11=Asayuki|last12=Saiwakawa|first12=Yutaka|last13=Kogawa|first13=Kazuhiro|last14=Yamanaka|first14=Junko|last15=Tsurusawa|first15=Masahito|title=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|journal=Pediatric Blood & Cancer|volume=57|issue=1|year=2011|pages=36–40|issn=15455009|doi=10.1002/pbc.22943}}</ref> | ||
| Line 13: | Line 13: | ||
'''''MC regimen:''''' | '''''MC regimen:''''' | ||
* Ara-C at 100 mg/m2 /day continuous infusion for 5 days and | *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 | *Mitoxantrone at 3.5 mg/m2 by 60 min infusion on days 2–4 | ||
'''''EC regimen''''' | '''''EC regimen''''' | ||
* High-dose Ara-C 1 g/m2 every 12 hrs on days 1–5, | *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 | *Etoposide 66 mg/m2 by 2 h infusion on days 2–4), and | ||
'''''AVC2 regimen''''' | '''''AVC2 regimen''''' | ||
* Ara-C at 100 mg/m2 /day on days 1–5, | *Ara-C at 100 mg/m2 /day on days 1–5, | ||
* Pirarubicin 35 mg/m2 by 60 min infusion on day 2, and | *Pirarubicin 35 mg/m2 by 60 min infusion on day 2, and | ||
* Vincristine at 0.7 mg/m2 on day 5 | *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 | 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.<ref name="De MarchiAraki20192">{{cite journal|last1=De Marchi|first1=Federico|last2=Araki|first2=Marito|last3=Komatsu|first3=Norio|title=Molecular features, prognosis, and novel treatment options for pediatric acute megakaryoblastic leukemia|journal=Expert Review of Hematology|volume=12|issue=5|year=2019|pages=285–293|issn=1747-4086|doi=10.1080/17474086.2019.1609351}}</ref> | ||
* 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.<ref name="AthaleRazzouk2001">{{cite journal|last1=Athale|first1=Uma H.|last2=Razzouk|first2=Bassem I.|last3=Raimondi|first3=Susana C.|last4=Tong|first4=Xin|last5=Behm|first5=Frederick G.|last6=Head|first6=David R.|last7=Srivastava|first7=Deo K.|last8=Rubnitz|first8=Jeffrey E.|last9=Bowman|first9=Laura|last10=Pui|first10=Ching-Hon|last11=Ribeiro|first11=Raul C.|title=Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience|journal=Blood|volume=97|issue=12|year=2001|pages=3727–3732|issn=1528-0020|doi=10.1182/blood.V97.12.3727}}</ref> | *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.<ref name="AthaleRazzouk2001">{{cite journal|last1=Athale|first1=Uma H.|last2=Razzouk|first2=Bassem I.|last3=Raimondi|first3=Susana C.|last4=Tong|first4=Xin|last5=Behm|first5=Frederick G.|last6=Head|first6=David R.|last7=Srivastava|first7=Deo K.|last8=Rubnitz|first8=Jeffrey E.|last9=Bowman|first9=Laura|last10=Pui|first10=Ching-Hon|last11=Ribeiro|first11=Raul C.|title=Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience|journal=Blood|volume=97|issue=12|year=2001|pages=3727–3732|issn=1528-0020|doi=10.1182/blood.V97.12.3727}}</ref> | ||
* 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).<ref name="SchweitzerZimmermann2015">{{cite journal|last1=Schweitzer|first1=Jana|last2=Zimmermann|first2=Martin|last3=Rasche|first3=Mareike|last4=von Neuhoff|first4=Christine|last5=Creutzig|first5=Ursula|last6=Dworzak|first6=Michael|last7=Reinhardt|first7=Dirk|last8=Klusmann|first8=Jan-Henning|title=Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial|journal=Annals of Hematology|volume=94|issue=8|year=2015|pages=1327–1336|issn=0939-5555|doi=10.1007/s00277-015-2383-2}}</ref> | *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).<ref name="SchweitzerZimmermann2015">{{cite journal|last1=Schweitzer|first1=Jana|last2=Zimmermann|first2=Martin|last3=Rasche|first3=Mareike|last4=von Neuhoff|first4=Christine|last5=Creutzig|first5=Ursula|last6=Dworzak|first6=Michael|last7=Reinhardt|first7=Dirk|last8=Klusmann|first8=Jan-Henning|title=Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial|journal=Annals of Hematology|volume=94|issue=8|year=2015|pages=1327–1336|issn=0939-5555|doi=10.1007/s00277-015-2383-2}}</ref> | ||
==References== | ==References== | ||
Revision as of 03:58, 19 April 2021
|
Acute megakaryoblastic leukemia Microchapters |
|
Differentiating Acute megakaryoblastic leukemia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Acute megakaryoblastic leukemia medical therapy On the Web |
|
American Roentgen Ray Society Images of Acute megakaryoblastic leukemia medical therapy |
|
Directions to Hospitals Treating Acute megakaryoblastic leukemia |
|
Risk calculators and risk factors for Acute megakaryoblastic leukemia 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.