Difference between revisions of "CNS leukemia"

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m (Text replacement - "*Cranial irradiation" to "*Whole-brain irradiation")
m
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=CNS prophylaxis=
 
=CNS prophylaxis=
  
−
==Cytarabine & Methotrexate {{#subobject:c47af4|Regimen=1}}==
+
==IT Cytarabine & Methotrexate {{#subobject:c47af4|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
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|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Methotrexate (MTX)]] 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
 
*[[Methotrexate (MTX)]] 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
 
*[[Cytarabine (Cytosar)]] 100 mg IT once on day 7
 
*[[Cytarabine (Cytosar)]] 100 mg IT once on day 7
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|}
 
|}
 
''Total number of doses depends on risk for CNS relapse based on serum lactate dehydrogenase (LDH) greater than 1400 IU/L and/or proliferative index percentage of S + G2M greater than or equal to 14%.''
 
''Total number of doses depends on risk for CNS relapse based on serum lactate dehydrogenase (LDH) greater than 1400 IU/L and/or proliferative index percentage of S + G2M greater than or equal to 14%.''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Methotrexate (MTX)]] 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
 
*[[Methotrexate (MTX)]] 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2
 
*[[Cytarabine (Cytosar)]] 100 mg IT once on day 7 or 8
 
*[[Cytarabine (Cytosar)]] 100 mg IT once on day 7 or 8
Line 75: Line 75:
 
## '''Update:''' Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29646/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666803/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26308885 PubMed]
 
## '''Update:''' Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29646/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666803/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26308885 PubMed]
  
−
==Cytarabine, Methotrexate, Methylprednisolone {{#subobject:eb3e09|Regimen=1}}==
+
==IT Cytarabine, Methotrexate, Methylprednisolone {{#subobject:eb3e09|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|}
 
|}
 
''Intrathecal treatments are given on days 1 & 8 of induction, day 29 of each series of consolidation blocks, and day 1 of late intensification -- 6 doses total.''
 
''Intrathecal treatments are given on days 1 & 8 of induction, day 29 of each series of consolidation blocks, and day 1 of late intensification -- 6 doses total.''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and methylprednisolone  
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and methylprednisolone  
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and methylprednisolone  
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and methylprednisolone  
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# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
 
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
  
−
==Cytarabine, Methotrexate, Prednisone {{#subobject:d81b63|Regimen=1}}==
+
==IT Cytarabine, Methotrexate, Prednisone {{#subobject:d81b63|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|}
 
|}
 
''Treatments were given after cycles 1, 3, and 5 after platelets greater than 70 × 10<sup>9</sup>/L and within 2 days before the next cycle.''
 
''Treatments were given after cycles 1, 3, and 5 after platelets greater than 70 × 10<sup>9</sup>/L and within 2 days before the next cycle.''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and prednisone  
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and prednisone  
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and prednisone
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and prednisone
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# Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13338/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25733162 PubMed]
 
# Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.13338/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25733162 PubMed]
  
−
==Cytarabine & WBRT {{#subobject:d62e53|Regimen=1}}==
+
==IT Cytarabine & WBRT {{#subobject:d62e53|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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## '''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [http://bloodjournal.hematologylibrary.org/content/123/6/843.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24277073 PubMed]
 
## '''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [http://bloodjournal.hematologylibrary.org/content/123/6/843.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24277073 PubMed]
  
−
==Mercaptopurine & WBRT {{#subobject:fab960|Regimen=1}}==
+
==IT Methotrexate monotherapy {{#subobject:98fb82|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
Mercaptopurine & WBRT: Mercaptopurine & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
===Regimen {{#subobject:846b99|Variant=1}}===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!Study
 
−
![[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 Huguet et al. 2009 (GRAALL-2003)]
 
−
|style="background-color:#91cf61"|Phase II
 
−
|-
 
−
|}
 
−
''Chemoradiation is given before maintenance therapy.''
 
−
====Chemoradiotherapy====
 
−
*[[Mercaptopurine (Purinethol)]] 60 mg/m<sup>2</sup>/day during irradiation
 
−
*[[External_beam_radiotherapy|Whole-brain irradiation]] to 18 Gy (details not provided)
 
−
 
 
−
'''One course'''
 
−
 
 
−
===References===
 
−
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
 
−
 
 
−
==Methotrexate monotherapy {{#subobject:98fb82|Regimen=1}}==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Methotrexate (MTX)]] as follows:
 
*[[Methotrexate (MTX)]] as follows:
 
**Phase 1: 12 mg IT once on day 15
 
**Phase 1: 12 mg IT once on day 15
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## '''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [http://bloodjournal.hematologylibrary.org/content/123/6/843.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24277073 PubMed]
 
## '''Update:''' Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. [http://bloodjournal.hematologylibrary.org/content/123/6/843.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916877/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24277073 PubMed]
  
−
==Methotrexate & Hydrocortisone {{#subobject:d0d04e|Regimen=1}}==
+
==IT Methotrexate & Hydrocortisone {{#subobject:d0d04e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|}
 
|}
 
''Treatment can be started during or after induction.''
 
''Treatment can be started during or after induction.''
−
====Chemotherapy====
+
====CNS chemotherapy====
−
*[[Methotrexate (MTX)]] 15 mg (schedule not specified), admixed with hydrocortisone
+
*[[Methotrexate (MTX)]] 15 mg IT (schedule not specified), admixed with hydrocortisone
 
*[[Hydrocortisone (Cortef)]] 50 mg IT (schedule not specified), admixed with methotrexate
 
*[[Hydrocortisone (Cortef)]] 50 mg IT (schedule not specified), admixed with methotrexate
  
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# Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. Epub 2015 Jun 11. [http://www.bloodjournal.org/content/126/6/746.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26065651 PubMed]
 
# Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. Epub 2015 Jun 11. [http://www.bloodjournal.org/content/126/6/746.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26065651 PubMed]
  
−
==Methotrexate & Methylprednisolone {{#subobject:6a4bad|Regimen=1}}==
+
==IT Methotrexate & Methylprednisolone {{#subobject:6a4bad|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|}
 
|}
 
''It is not explicitly stated but presumably these are admixed and given together.''
 
''It is not explicitly stated but presumably these are admixed and given together.''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Methotrexate (MTX)]] 12 mg IT once prior to each consolidation cycle
 
*[[Methotrexate (MTX)]] 12 mg IT once prior to each consolidation cycle
 
*[[Methylprednisolone (Solumedrol)]] 40 mg IT once prior to each consolidation cycle
 
*[[Methylprednisolone (Solumedrol)]] 40 mg IT once prior to each consolidation cycle
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# Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. [http://www.bloodjournal.org/content/116/17/3171.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20644121 PubMed]
 
# Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. [http://www.bloodjournal.org/content/116/17/3171.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20644121 PubMed]
  
−
==Methotrexate & WBRT {{#subobject:4b9a67|Regimen=1}}==
+
==IT Methotrexate & WBRT {{#subobject:4b9a67|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
Methotrexate & WBRT: Methotrexate & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+
IT Methotrexate & WBRT: '''<u>I</u>'''ntra'''<u>T</u>'''hecal Methotrexate & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
===Regimen {{#subobject:b1f086|Variant=1}}===
 
===Regimen {{#subobject:b1f086|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
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# Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. [http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3470055 PubMed]
 
# Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. [http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3470055 PubMed]
 
## '''Update:''' Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. [http://bloodjournal.hematologylibrary.org/content/78/11/2814.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1835410 PubMed]
 
## '''Update:''' Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. [http://bloodjournal.hematologylibrary.org/content/78/11/2814.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1835410 PubMed]
 +
 +
==Mercaptopurine & WBRT {{#subobject:fab960|Regimen=1}}==
 +
{| class="wikitable" style="float:right; margin-left: 5px;"
 +
|-
 +
|[[#top|back to top]]
 +
|}
 +
Mercaptopurine & WBRT: Mercaptopurine & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
===Regimen {{#subobject:846b99|Variant=1}}===
 +
{| class="wikitable" style="width: 100%; text-align:center;"
 +
!Study
 +
![[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 Huguet et al. 2009 (GRAALL-2003)]
 +
|style="background-color:#91cf61"|Phase II
 +
|-
 +
|}
 +
''Chemoradiation is given before maintenance therapy.''
 +
====Chemoradiotherapy====
 +
*[[Mercaptopurine (Purinethol)]] 60 mg/m<sup>2</sup>/day PO during irradiation
 +
*[[External_beam_radiotherapy|Whole-brain irradiation]] to 18 Gy (details not provided)
 +
 +
'''One course'''
 +
 +
===References===
 +
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
  
 
=CNS treatment=
 
=CNS treatment=
  
−
==Cytarabine & Methotrexate {{#subobject:7536ce|Regimen=1}}==
+
==IT Cytarabine & Methotrexate {{#subobject:7536ce|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
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|}
 
|}
 
''Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).''
 
''Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Methotrexate (MTX)]] as follows:
 
*[[Methotrexate (MTX)]] as follows:
 
**Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
 
**Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
Line 310: Line 310:
 
# Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. [http://jco.ascopubs.org/content/17/8/2461.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10561310 PubMed]
 
# Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. [http://jco.ascopubs.org/content/17/8/2461.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10561310 PubMed]
  
−
==Cytarabine, Methotrexate, Methylprednisolone {{#subobject:833d98|Regimen=1}}==
+
==IT Cytarabine, Methotrexate, Methylprednisolone {{#subobject:833d98|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 325: Line 325:
 
|}
 
|}
 
''Intrathecal treatments are given as follows: eight between days −7 and 21 of induction, four during the first two consolidation blocks, and one at day 29 of consolidation blocks 3 and 6 -- 14 total doses.''
 
''Intrathecal treatments are given as follows: eight between days −7 and 21 of induction, four during the first two consolidation blocks, and one at day 29 of consolidation blocks 3 and 6 -- 14 total doses.''
−
====Chemotherapy====
+
====CNS chemotherapy====
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and methylprednisolone  
 
*[[Cytarabine (Cytosar)]] 40 mg IT mixed with methotrexate and methylprednisolone  
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and methylprednisolone  
 
*[[Methotrexate (MTX)]] 15 mg IT mixed with cytarabine and methylprednisolone  
Line 335: Line 335:
 
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
 
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
  
−
==Cytarabine, Methotrexate, WBRT {{#subobject:2457a6|Regimen=1}}==
+
==IT Cytarabine, Methotrexate, WBRT {{#subobject:2457a6|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 363: Line 363:
 
**First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
 
**First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
 
**Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle
 
**Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle
−
*Therapeutic external radiation is given to patients with CNS disease at presentation
+
*Therapeutic [[External_beam_radiotherapy|whole-brain irradiation]] is given to patients with CNS disease at presentation
  
 
===References===
 
===References===
Line 371: Line 371:
 
## '''Update:''' Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29646/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666803/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26308885 PubMed]
 
## '''Update:''' Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.29646/full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666803/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26308885 PubMed]
  
−
==Mercaptopurine & WBRT {{#subobject:d6ba9e|Regimen=1}}==
+
==IT Methotrexate monotherapy {{#subobject:d4a3c5|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
Mercaptopurine & WBRT: Mercaptopurine & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+
===Regimen {{#subobject:183c87|Variant=1}}===
−
===Regimen {{#subobject:cd21c7|Variant=1}}===
 
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
!Study
 
!Study
Line 386: Line 385:
 
|-
 
|-
 
|}
 
|}
−
''Treatment administered before HSCT or maintanence initiation.''
+
====Chemotherapy====
−
====Chemoradiotherapy====
+
*[[Methotrexate (MTX)]] as follows:
−
*[[Mercaptopurine (Purinethol)]] 60 mg/m<sup>2</sup>/day during irradiation
+
**Prephase: 15 mg IT once at some point between days -7 and -4
−
*[[External_beam_radiotherapy|Whole-brain irradiation]] as follows:
 
−
**15 Gy before HCT (details not provided), or
 
−
**24 Gy before maintenance therapy initiation (details not provided)
 
−
 
 
−
'''One course'''
 
  
 
===References===
 
===References===
 
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
 
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
  
−
==Methotrexate monotherapy {{#subobject:d4a3c5|Regimen=1}}==
+
==IT Methotrexate & WBRT {{#subobject:d129ea|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
===Regimen {{#subobject:183c87|Variant=1}}===
+
IT Methotrexate & WBRT: '''<u>I</u>'''ntra'''<u>T</u>'''hecal Methotrexate & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
===Regimen {{#subobject:f7b824|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
!Study
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 Huguet et al. 2009 (GRAALL-2003)]
+
|[http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html Linker et al. 1987]
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
''Treatment starts while patient is receiving induction therapy.''
 +
====Chemoradiotherapy====
 
*[[Methotrexate (MTX)]] as follows:
 
*[[Methotrexate (MTX)]] as follows:
−
**Prephase: 15 mg IT once at some point between days -7 and -4
+
**Induction: 12 mg IT once per week x 10 doses
 +
**Remainder of first year of therapy: 12 mg IT once per month
 +
*[[External_beam_radiotherapy|Whole-brain irradiation]], 28 Gy total given (no details provided)
  
 
===References===
 
===References===
−
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
+
# Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. [http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3470055 PubMed]
 +
## '''Update:''' Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. [http://bloodjournal.hematologylibrary.org/content/78/11/2814.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1835410 PubMed]
  
−
==Methotrexate & WBRT {{#subobject:d129ea|Regimen=1}}==
+
==Mercaptopurine & WBRT {{#subobject:d6ba9e|Regimen=1}}==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
Methotrexate & WBRT: Methotrexate & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+
Mercaptopurine & WBRT: Mercaptopurine & '''<u>W</u>'''hole '''<u>B</u>'''rain '''<u>R</u>'''adiation '''<u>T</u>'''herapy
−
===Regimen {{#subobject:f7b824|Variant=1}}===
+
===Regimen {{#subobject:cd21c7|Variant=1}}===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
!Study
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html Linker et al. 1987]
+
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 Huguet et al. 2009 (GRAALL-2003)]
 
|style="background-color:#91cf61"|Phase II
 
|style="background-color:#91cf61"|Phase II
 
|-
 
|-
 
|}
 
|}
−
''Treatment starts while patient is receiving induction therapy.''
+
''Treatment administered before HSCT or maintanence initiation.''
 
====Chemoradiotherapy====
 
====Chemoradiotherapy====
−
*[[Methotrexate (MTX)]] as follows:
+
*[[Mercaptopurine (Purinethol)]] 60 mg/m<sup>2</sup>/day PO during irradiation
−
**Induction: 12 mg IT once per week x 10 doses
+
*[[External_beam_radiotherapy|Whole-brain irradiation]] as follows:
−
**Remainder of first year of therapy: 12 mg IT once per month
+
**15 Gy before HCT (details not provided), or
−
*[[External_beam_radiotherapy|Whole-brain irradiation]], 28 Gy total given (no details provided)
+
**24 Gy before maintenance therapy initiation (details not provided)
 +
 
 +
'''One course'''
  
 
===References===
 
===References===
−
# Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. [http://bloodjournal.hematologylibrary.org/content/69/4/1242.full.pdf+html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3470055 PubMed]
+
# '''GRAALL-2003:''' Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. [http://ascopubs.org/doi/full/10.1200/JCO.2015.61.5385 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19124805 PubMed]
−
## '''Update:''' Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. [http://bloodjournal.hematologylibrary.org/content/78/11/2814.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1835410 PubMed]
 
  
 
[[Category:CNS leukemia regimens]]
 
[[Category:CNS leukemia regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:CNS cancers]]
 
[[Category:CNS cancers]]

Revision as of 21:02, 19 June 2018


Section editor
SeemaNagpal.jpg
 Seema Nagpal, MD
Palo Alto, CA
16 regimens on this page
19 variants on this page


Note: these regimens are primarily culled from literature that describes them as part of a comprehensive treatment regimen. If that is the case, the original regimens can be found on the following pages:

CNS prophylaxis

IT Cytarabine & Methotrexate

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Variant #1, 16 doses

Study Evidence
Thomas et al. 2006 Pilot, <20 pts

CNS chemotherapy

Given each cycle for a total of 16 intrathecal treatments

Variant #2, 6 to 8 doses

Study Evidence
Thomas et al. 1999 Phase II
Thomas et al. 2003 Phase II
Ravandi et al. 2010 Phase II

Total number of doses depends on risk for CNS relapse based on serum lactate dehydrogenase (LDH) greater than 1400 IU/L and/or proliferative index percentage of S + G2M greater than or equal to 14%.

CNS chemotherapy

Given each cycle (approximately every 3 weeks) for a total of 6 or 8 intrathecal treatments

References

  1. Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. link to original article contains verified protocol PubMed
  2. Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. Epub 2003 Oct 9. link to original article contains verified protocol PubMed
    1. Update: Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O' Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the frontline treatment of adult patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. Epub 2015 Feb 14. link to original article link to PMC article PubMed
  3. Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. link to original article contains verified protocol PubMed
    1. Update: Fayad L, Thomas D, Romaguera J. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma. 2007 Dec;8 Suppl 2:S57-62. PubMed
  4. Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010 Sep 23;116(12):2070-7. Epub 2010 May 13. link to original article contains verified protocol--parts of the protocol were not explicitly listed in this reference, which instead referred to Thomas et al. 2004 and Kantarjian et al. 2004 link to PMC article PubMed
    1. Update: Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. link to original article link to PMC article PubMed

IT Cytarabine, Methotrexate, Methylprednisolone

back to top

Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Intrathecal treatments are given on days 1 & 8 of induction, day 29 of each series of consolidation blocks, and day 1 of late intensification -- 6 doses total.

CNS chemotherapy

6 doses

References

  1. GRAALL-2003: Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to original article contains verified protocol PubMed

IT Cytarabine, Methotrexate, Prednisone

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Regimen

Study Evidence
Tsukasaki et al. 2007 (JCOG 9801) Non-randomized
Ishida et al. 2015 Non-randomized

Treatments were given after cycles 1, 3, and 5 after platelets greater than 70 × 109/L and within 2 days before the next cycle.

CNS chemotherapy

3 doses

References

  1. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains verified protocol PubMed
  2. Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. link to original article link to PMC article PubMed

IT Cytarabine & WBRT

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Cytarabine & WBRT: Cytarabine & Whole Brain Radiation Therapy

Regimen

Study Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Non-randomized portion of RCT

Note: while this is not chemoradiation in the traditional sense, the delivery of chemotherapy and radiation overlap so may have synergistic effects.

Chemoradiotherapy

References

  1. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed

IT Methotrexate monotherapy

back to top

Regimen

Study Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Non-randomized portion of RCT

CNS chemotherapy

  • Methotrexate (MTX) as follows:
    • Phase 1: 12 mg IT once on day 15
    • Phase 2: 12 mg IT once per day on days 1, 8, 15, 22

References

  1. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article link to PMC article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol link to PMC article PubMed

IT Methotrexate & Hydrocortisone

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Regimen

Study Evidence
Kim et al. 2015 Phase II

Treatment can be started during or after induction.

CNS chemotherapy

Up to 10 doses

References

  1. Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. Epub 2015 Jun 11. link to original article contains verified protocol PubMed

IT Methotrexate & Methylprednisolone

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Regimen

Study Evidence
Lo-Coco et al. 2010 Non-randomized

It is not explicitly stated but presumably these are admixed and given together.

CNS chemotherapy

Total of 3 doses

References

  1. Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. link to original article contains verified protocol PubMed

IT Methotrexate & WBRT

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IT Methotrexate & WBRT: IntraThecal Methotrexate & Whole Brain Radiation Therapy

Regimen

Study Evidence
Linker et al. 1987 Phase II

Treatment is started within 1 week of achieving complete remission.

Chemoradiotherapy

References

  1. Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. link to original article contains verified protocol PubMed
    1. Update: Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. link to original article contains verified protocol PubMed

Mercaptopurine & WBRT

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Mercaptopurine & WBRT: Mercaptopurine & Whole Brain Radiation Therapy

Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Chemoradiation is given before maintenance therapy.

Chemoradiotherapy

One course

References

  1. GRAALL-2003: Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to original article contains verified protocol PubMed

CNS treatment

IT Cytarabine & Methotrexate

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Regimen

Study Evidence
Thomas et al. 1999 Phase II

Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).

CNS chemotherapy

  • Methotrexate (MTX) as follows:
    • Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
    • First 4 weeks after cell count & cytology are negative: 12 mg (6 mg if given via Ommaya reservoir) IT once per week on weeks 1 & 3
    • Remainder of induction: 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2 of each cycle
  • Cytarabine (Cytosar) as follows:
    • Measurable CNS disease: 100 mg IT once per week
    • First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
    • Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle

References

  1. Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. link to original article contains verified protocol PubMed

IT Cytarabine, Methotrexate, Methylprednisolone

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Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Intrathecal treatments are given as follows: eight between days −7 and 21 of induction, four during the first two consolidation blocks, and one at day 29 of consolidation blocks 3 and 6 -- 14 total doses.

CNS chemotherapy

14 doses

References

  1. GRAALL-2003: Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to original article contains verified protocol PubMed

IT Cytarabine, Methotrexate, WBRT

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Cytarabine, Methotrexate, WBRT: Cytarabine, Methotrexate, Whole Brain Radiation Therapy

Regimen

Study Evidence
Thomas et al. 2003 Phase II
Ravandi et al. 2010 Phase II

Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).

Chemoradiotherapy

  • Methotrexate (MTX) as follows:
    • Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
    • First 4 weeks after cell count & cytology are negative: 12 mg (6 mg if given via Ommaya reservoir) IT once per week on weeks 1 & 3
    • Remainder of induction: 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2 of each cycle
  • Cytarabine (Cytosar) as follows:
    • Measurable CNS disease: 100 mg IT once per week
    • First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
    • Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle
  • Therapeutic whole-brain irradiation is given to patients with CNS disease at presentation

References

  1. Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. Epub 2003 Oct 9. link to original article contains verified protocol PubMed
    1. Update: Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O' Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the frontline treatment of adult patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. Epub 2015 Feb 14. link to original article link to PMC article PubMed
  2. Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010 Sep 23;116(12):2070-7. Epub 2010 May 13. link to original article contains verified protocol--parts of the protocol were not explicitly listed in this reference, which instead referred to Thomas et al. 2004 and Kantarjian et al. 2004 link to PMC article PubMed
    1. Update: Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. link to original article link to PMC article PubMed

IT Methotrexate monotherapy

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Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Chemotherapy

  • Methotrexate (MTX) as follows:
    • Prephase: 15 mg IT once at some point between days -7 and -4

References

  1. GRAALL-2003: Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to original article contains verified protocol PubMed

IT Methotrexate & WBRT

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IT Methotrexate & WBRT: IntraThecal Methotrexate & Whole Brain Radiation Therapy

Regimen

Study Evidence
Linker et al. 1987 Phase II

Treatment starts while patient is receiving induction therapy.

Chemoradiotherapy

References

  1. Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. link to original article contains verified protocol PubMed
    1. Update: Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. link to original article contains verified protocol PubMed

Mercaptopurine & WBRT

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Mercaptopurine & WBRT: Mercaptopurine & Whole Brain Radiation Therapy

Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Treatment administered before HSCT or maintanence initiation.

Chemoradiotherapy

One course

References

  1. GRAALL-2003: Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to original article contains verified protocol PubMed
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