Difference between revisions of "B-cell acute lymphoblastic leukemia - historical"

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[B-cell acute lymphoblastic leukemia|main B-ALL page]] for current regimens.
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[B-cell acute lymphoblastic leukemia|main B-ALL page]] for current regimens.
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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=Upfront induction therapy=
 
=Upfront induction therapy=
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==Aminopterin monotherapy {{#subobject:1cf0b5|Regimen=1}}==
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==Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
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<div class="toccolours" style="background-color:#ee6b6e">
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|-
 
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|[[#top|back to top]]
 
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|}
 
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===Regimen {{#subobject:be57ed|Variant=1}}===
 
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{| class="wikitable" style="width: 50%; text-align:center;"
 
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!style="width: 25%"|Study
 
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
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|[https://www.nejm.org/doi/10.1056/NEJM194806032382301 Farber et al. 1948]
 
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| style="background-color:#ffffbe" |Non-randomized pilot
 
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|-
 
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|}
 
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''Of major historical interest, being one of the first published cancer chemotherapy experiments in man that led to an active non-clinical-trial intervention (to be distinguished from the trial of diopterin and teropterin [http://science.sciencemag.org/content/106/2764/619.long published in Science in 1947]). This agent is no longer available but was used clinically for several decades.''
 
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====Chemotherapy====
 
−
*[[Aminopterin]]
 
−
 
 
−
===References===
 
−
# Farber S, Mercer RD, Sylvester RF, Wolff JA, Diamond LK. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med. 1948 Jun 3;238(23):787-93. [https://www.nejm.org/doi/10.1056/NEJM194806032382301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18860765 PubMed]
 
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==COMP {{#subobject:2ec876|Regimen=1}}==
 
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COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
 
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===Regimen {{#subobject:0ecc0a|Variant=1}}===
 
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{| class="wikitable" style="width: 100%; text-align:center;"
 
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!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
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!style="width: 25%"|Comparator
 
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!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
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|-
 
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|[https://www.nejm.org/doi/full/10.1056/NEJM198303103081003 Anderson et al. 1983]
 
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| style="background-color:#1a9851" |Phase III (E)
 
−
|Modified LSA<sub>2</sub>-L<sub>2</sub>
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
===References===
 
−
# Anderson JR, Wilson JF, Jenkin DT, Meadows AT, Kersey J, Chilcote RR, Coccia P, Exelby P, Kushner J, Siegel S, Hammond D. Childhood non-Hodgkin's lymphoma: the results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med. 1983 Mar 10;308(10):559-65. [https://www.nejm.org/doi/full/10.1056/NEJM198303103081003 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6338381 PubMed]
 
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==Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
 
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{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|-
 
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|[[#top|back to top]]
 
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|}
 
 
===Regimen {{#subobject:0f2246|Variant=1}}===
 
===Regimen {{#subobject:0f2246|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
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{| class="wikitable" style="width: 60%; text-align:center;"  
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!style="width: 25%"|Study
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!style="width: 33%"|Study
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
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|[https://www.nature.com/leu/journal/v16/n7/full/2402526a.html Takeuchi et al. 2002 (JALSG-ALL93)]
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|[https://doi.org/10.1038/sj.leu.2402526 Takeuchi et al. 2002 (JALSG-ALL93)]
 +
|1993-1997
 
|style="background-color:#91cf61"|Non-randomized
 
|style="background-color:#91cf61"|Non-randomized
 
|-
 
|-
 
|}
 
|}
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''Unlikely to be completed, here for historic context only.''
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<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]]
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*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 29
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*[[Doxorubicin (Adriamycin)]]
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*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 3, 8 to 10
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*[[Asparaginase (Elspar)|L-Asparaginase]]
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*[[Asparaginase (Elspar)|L-Asparaginase]] 6000 IU/m<sup>2</sup> IV once per day on days 29 to 35
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*[[Vincristine (Oncovin)]]
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*[[Vincristine (Oncovin)]] 1.3 mg/m<sup>2</sup> (maximum dose of 2 mg) IV bolus once per day on days 1, 8, 15, 22
−
*[[Prednisolone (Millipred)]]
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====Glucocorticoid therapy====
−
 
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*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 10
−
===References===
+
====Supportive therapy====
−
# '''JALSG-ALL93:''' Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002 Jul;16(7):1259-66. [https://www.nature.com/leu/journal/v16/n7/full/2402526a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12094249 PubMed]
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*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 200 mcg/m<sup>2</sup> IV once per day on days 12 to 26
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'''35-day course'''
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==Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone {{#subobject:5a7eda|Regimen=1}}==
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</div>
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{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#cbd5e8">
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|-
 
−
|[[#top|back to top]]
 
−
|}
 
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===Regimen {{#subobject:245098|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PIIS014067360761126X/fulltext Pieters et al. 2007 (Interfant-99)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
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====Preceding treatment====
 
−
*Prednisone pre-phase
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]]
 
−
*[[Daunorubicin (Cerubidine)]]
 
−
*[[Asparaginase (Elspar)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Dexamethasone (Decadron)]]
 
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*MARAM consolidation
+
*Consolidation I (see paper for details)
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''Interfant-99:''' Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, Hovi L, LeBlanc T, Szczepanski T, Ferster A, Janka G, Rubnitz J, Silverman L, Stary J, Campbell M, Li CK, Mann G, Suppiah R, Biondi A, Vora A, Valsecchi MG. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007 Jul 21;370(9583):240-250. [https://www.thelancet.com/journals/lancet/article/PIIS014067360761126X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17658395 PubMed]
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# '''JALSG-ALL93:''' Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002 Jul;16(7):1259-66. [https://doi.org/10.1038/sj.leu.2402526 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12094249/ PubMed]
  
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==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone {{#subobject:177f43|Regimen=1}}==
+
==Idarubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:54jbs9|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#ee6b6e">
−
|-
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===Regimen {{#subobject:3y2de2|Variant=1}}===
−
|[[#top|back to top]]
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{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
|}
+
!style="width: 20%"|Study
−
===Regimen {{#subobject:2c8cee|Variant=1}}===
+
!style="width: 20%"|Dates of enrollment
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|Study
+
!style="width: 20%"|Comparator
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90733-6/abstract Rivera et al. 1991]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJM199802193380803 Evans et al. 1998]
+
|[https://doi.org/10.1182/blood-2003-10-3560 Hunault et al. 2004 (GOELAL02)]
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
|1994-1998
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Idarubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Idarubicin, L-asparaginase, Vincristine, Prednisone]]; oral prednisone
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of response rate
 
|-
 
|-
 
|}
 
|}
 +
''Note: This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]]
+
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
−
*[[Daunorubicin (Cerubidine)]]
+
*[[Asparaginase (Elspar)]] 7500 IU/m<sup>2</sup> IV once per day on days 10, 13, 16, 19, 22, 25
−
*[[Asparaginase (Elspar)]]
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*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
−
*[[Teniposide (Vumon)]]
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====Glucocorticoid therapy====
−
*[[Vincristine (Oncovin)]]
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*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO or IV once per day on days 1 to 21
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*[[Prednisone (Sterapred)]]
+
'''35-day course'''
−
====Subsequent treatment====
+
</div></div>
−
*High-dose MTX
 
−
 
 
 
===References===
 
===References===
−
# Rivera GK, Raimondi SC, Hancock ML, Behm FG, Pui CH, Abromowitch M, Mirro J Jr, Ochs JS, Look AT, Williams DL, Murphy SB, Dahl GV, Kalwinsky DK, Evans WE, Kun LE, Simone JV, Crist WM. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. Lancet. 1991 Jan 12;337(8733):61-6. [https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90733-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1670723 PubMed]
+
#'''GOELAL02:''' Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, Lamy T, Pignon B, Jouet JP, Garidi R, Caillot D, Berthou C, Guyotat D, Sadoun A, Sotto JJ, Lioure B, Casassus P, Solal-Celigny P, Stalnikiewicz L, Audhuy B, Blanchet O, Baranger L, Béné MC, Ifrah N; GOELAMS (Groupe Ouest-Est des Leucémies Airguës et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004 Nov 15;104(10):3028-37. Epub 2004 Jul 15. [https://doi.org/10.1182/blood-2003-10-3560 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15256423/ PubMed] [https://clinicaltrials.gov/study/NCT00483132 NCT00483132]
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# Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med. 1998 Feb 19;338(8):499-505. [https://www.nejm.org/doi/full/10.1056/NEJM199802193380803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9468466 PubMed]
 
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==Doxorubicin, Methotrexate, Vincristine, Prednisone {{#subobject:96590c|Regimen=1}}==
 
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{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:dee4bf|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM198609113151101 Clavell et al. 1986]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Prednisone (Sterapred)]]
 
−
 
 
−
===References===
 
−
# Clavell LA, Gelber RD, Cohen HJ, Hitchcock-Bryan S, Cassady JR, Tarbell NJ, Blattner SR, Tantravahi R, Leavitt P, Sallan SE. Four-agent induction and intensive asparaginase therapy for treatment of childhood acute lymphoblastic leukemia. N Engl J Med. 1986 Sep 11;315(11):657-63. [https://www.nejm.org/doi/full/10.1056/NEJM198609113151101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2943992 PubMed]
 
−
 
 
−
==L-Asparaginase, Vincristine, Dexamethasone {{#subobject:54ea09|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen {{#subobject:4c9de2|Variant=1}}===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|Comparator
 
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.3.911 Veerman et al. 1996 (DCOG ALL-VI)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/101/10/3809.long Bostrom et al. 2003 (CCG-1922)]
 
−
|style="background-color:#1a9851"|Phase III (E)
 
−
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-asparaginase, Vincristine, Prednisone]]
 
−
|style="background-color:#1a9850"|Superior EFS
 
−
|-
 
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full Mitchell et al. 2005 (UK MRC ALL97)]
 
−
|style="background-color:#1a9851"|Phase III (E)
 
−
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisolone|L-asparaginase, Vincristine, Prednisolone]]
 
−
|style="background-color:#1a9850"|Superior EFS
 
−
|-
 
−
|[https://www.sciencedirect.com/science/article/pii/S1470204509702281 Veerman et al. 2009 (DCOG ALL-9)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Unlikely to be completed, here for historic context only.''
 
−
====Chemotherapy====
 
−
*[[Asparaginase (Elspar)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Dexamethasone (Decadron)]]
 
−
 
 
−
===References===
 
−
# '''DCOG ALL-VI:''' Veerman AJ, Hählen K, Kamps WA, Van Leeuwen EF, De Vaan GA, Solbu G, Suciu S, Van Wering ER, Van der Does-Van der Berg A. High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia: results of protocol ALL VI from the Dutch Childhood Leukemia Study Group. J Clin Oncol. 1996 Mar;14(3):911-8. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.3.911 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8622039 PubMed]
 
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# '''CCG-1922:''' Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. [http://www.bloodjournal.org/content/101/10/3809.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12531809 PubMed]
 
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# '''UK MRC ALL97:''' Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15952999 PubMed]
 
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## '''Update:''' Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM; Medical Research Council; National Cancer Research Network Childhood Leukaemia Working Party. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet. 2006 Oct 14;368(9544):1339-48. [https://www.thelancet.com/journals/lancet/article/PIIS0140673606695585/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17046466 PubMed]
 
−
# '''DCOG ALL-9:''' Veerman AJ, Kamps WA, van den Berg H, van den Berg E, Bökkerink JP, Bruin MC, van den Heuvel-Eibrink MM, Korbijn CM, Korthof ET, van der Pal K, Stijnen T, van Weel Sipman MH, van Weerden JF, van Wering ER, van der Does-van den Berg A; Dutch Childhood Oncology Group. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004). Lancet Oncol. 2009 Oct;10(10):957-66. Epub 2009 Sep 9. [https://www.sciencedirect.com/science/article/pii/S1470204509702281 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/19747876 PubMed]
 
−
 
 
−
==L-Asparaginase, Vincristine, Prednisolone {{#subobject:65692a|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:4af0d5|Variant=1}}===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|Comparator
 
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.nature.com/articles/2401704 Hann et al. 2000 (MRC UKALL XI)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full Mitchell et al. 2005 (UK MRC ALL97)]
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
 
−
|style="background-color:#d73027"|Inferior EFS
 
−
|-
 
−
|}
 
−
''Unlikely to be completed, here for historic context only.''
 
−
====Chemotherapy====
 
−
*[[Asparaginase (Elspar)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Prednisolone (Millipred)]]
 
−
 
 
−
===References===
 
−
# '''MRC UKALL XI:''' Hann I, Vora A, Richards S, Hill F, Gibson B, Lilleyman J, Kinsey S, Mitchell C, Eden OB; UK Medical Research Council's Working Party on Childhood Leukaemia. Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. Leukemia. 2000 Mar;14(3):356-63. [https://www.nature.com/articles/2401704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10720126 PubMed]
 
−
# '''UK MRC ALL97:''' Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15952999 PubMed]
 
−
## '''Update:''' Vora A, Mitchell CD, Lennard L, Eden TO, Kinsey SE, Lilleyman J, Richards SM; Medical Research Council; National Cancer Research Network Childhood Leukaemia Working Party. Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial. Lancet. 2006 Oct 14;368(9544):1339-48. [https://www.thelancet.com/journals/lancet/article/PIIS0140673606695585/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17046466 PubMed]
 
  
 
==L-Asparaginase, Vincristine, Prednisone {{#subobject:d039d8|Regimen=1}}==
 
==L-Asparaginase, Vincristine, Prednisone {{#subobject:d039d8|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:a4174a|Variant=1}}===
 
===Regimen {{#subobject:a4174a|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Dates of enrollment
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.sciencedirect.com/science/article/pii/0145212679900365 Henderson et al. 1979 (CALGB 7113)]
+
|[https://doi.org/10.1016/0145-2126(79)90036-5 Henderson et al. 1979 (CALGB 7113)]
 +
|1971-1976
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
 
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/64/1/267.long Gottlieb et al. 1984 (CALGB 7612)]
+
|[https://doi.org/10.1182/blood.V64.1.267.267 Gottlieb et al. 1984 (CALGB 7612)]
 +
|1976-1980
 
|style="background-color:#1a9851"|Randomized (C)
 
|style="background-color:#1a9851"|Randomized (C)
 
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 
|style="background-color:#d73027"|Inferior CR rate
 
|style="background-color:#d73027"|Inferior CR rate
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pubmed/2665546 van der Does-van den Berg et al. 1989 (DCLSG ALL V)]
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1991.tb04415.x Eden et al. 1991 (MRC UKALL VIII)]
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 
−
|style="background-color:#ffffbf"|Seems not superior
 
−
|-
 
−
|[https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.3.527 Tubergen et al. 1993 (CCG-105)]
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|-
 
−
|[http://www.bloodjournal.org/content/101/10/3809.long Bostrom et al. 2003 (CCG-1922)]
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
 
−
|style="background-color:#d73027"|Inferior EFS
 
 
|-
 
|-
 
|}
 
|}
−
''Unlikely to be completed, here for historic context only.''
+
''Note: The asparaginase dosing shown here was that after a mid-protocol amendment due to excess toxicity.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Asparaginase (Elspar)]]
+
*[[Asparaginase (Elspar)]] 500 IU/kg IV once per day on days 16 to 25
−
*[[Vincristine (Oncovin)]]
+
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1, 8, 15
−
*[[Prednisone (Sterapred)]]
+
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 21, then tapered off over days 22 to 28
 +
'''28-day course'''
 +
</div></div>
  
 
===References===
 
===References===
−
# '''CALGB 7113:''' Henderson ES, Scharlau C, Cooper MR, Haurani FI, Silver RT, Brunner K, Carey RW, Falkson G, Blom J, Nawabi IV, Levine AS, Bank A, Cuttner J, Cornwell GG 3rd, Henry P, Nissen NI, Wiernik PH, Leone L, Wohl H, Rai K, James GW, Weinberg V, Glidewell O, Holland JF. Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113. Leuk Res. 1979;3(6):395-407. [https://www.sciencedirect.com/science/article/pii/0145212679900365 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/297176 PubMed]
+
# '''CALGB 7113:''' Henderson ES, Scharlau C, Cooper MR, Haurani FI, Silver RT, Brunner K, Carey RW, Falkson G, Blom J, Nawabi IV, Levine AS, Bank A, Cuttner J, Cornwell GG 3rd, Henry P, Nissen NI, Wiernik PH, Leone L, Wohl H, Rai K, James GW, Weinberg V, Glidewell O, Holland JF. Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113. Leuk Res. 1979;3(6):395-407. [https://doi.org/10.1016/0145-2126(79)90036-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/297176/ PubMed]
−
# '''CALGB 7612:''' Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN, Hutchinson JL, Raich P, Cooper MR, Wiernik P, Anderson JR, Holland JF. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984 Jul;64(1):267-74. [http://www.bloodjournal.org/content/64/1/267.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6375760 PubMed]
+
# '''CALGB 7612:''' Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN, Hutchinson JL, Raich P, Cooper MR, Wiernik P, Anderson JR, Holland JF. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984 Jul;64(1):267-74. [https://doi.org/10.1182/blood.V64.1.267.267 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6375760/ PubMed]
−
# '''DCLSG ALL V:''' van der Does-van den Berg A, van Wering ER, Suciu S, Solbu G, van 't Veer MB, Rammeloo JA, de Koning J, van Zanen GE. Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V); A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG). Am J Pediatr Hematol Oncol. 1989 Summer;11(2):125-33. [https://www.ncbi.nlm.nih.gov/pubmed/2665546 PubMed]
 
−
# '''MRC UKALL VIII:''' Eden OB, Lilleyman JS, Richards S, Shaw MP, Peto J. Results of Medical Research Council Childhood Leukaemia Trial UKALL VIII (report to the Medical Research Council on behalf of the Working Party on Leukaemia in Childhood). Br J Haematol. 1991 Jun;78(2):187-96. [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1991.tb04415.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2064956 PubMed]
 
−
# '''CCG-105:''' Tubergen DG, Gilchrist GS, O'Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, Hammond GD. Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: a Childrens Cancer Group phase III trial. J Clin Oncol. 1993 Mar;11(3):527-37. [https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.3.527 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8445428 PubMed]
 
−
# '''CCG-1922:''' Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. [http://www.bloodjournal.org/content/101/10/3809.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12531809 PubMed]
 
  
 
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
 
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:1fc958|Variant=1}}===
 
===Regimen {{#subobject:1fc958|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Dates of enrollment
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/13/12/1126.long Frei et al. 1958 (ALGB 01)]
+
|[https://doi.org/10.1182/blood.V13.12.1126.1126 Frei et al. 1958 (ALGB 01)]
−
|style="background-color:#1a9851"|Randomized (E)
+
|Not reported
−
|6-MP & MTX (alternate dosing)
+
|style="background-color:#1a9851"|Randomized (E-switch-ic)
−
|style="background-color:#ffffbf"|Seems not superior
+
|[[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]; alternate dosing
 +
|style="background-color:#ffffbf"|Did not meet endpoints
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/18/4/431.short Frei et al. 1961 (ALGB 03)]
+
|[https://doi.org/10.1182/blood.V18.4.431.431 Frei et al. 1961 (ALGB 03)]
−
|style="background-color:#1a9851"|Randomized (E)
+
|1957-1960
−
|1. 6-MP<br> 2. MTX
+
|style="background-color:#1a9851"|Randomized (E-esc)
−
|style="background-color:#ffffbf"|Seems not superior
+
|1. [[#Mercaptopurine_monotherapy_888|6-MP]]<br>2. [[#Methotrexate_monotherapy_888|MTX]]
−
|-
+
|style="background-color:#ffffbf"|Did not meet endpoint of DOR
−
|[http://www.bloodjournal.org/content/26/5/642.long Frei et al. 1965]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
 
|-
 
|-
 
|}
 
|}
 
''Note: this is one of the first combination regimens in hematology/oncology.''
 
''Note: this is one of the first combination regimens in hematology/oncology.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mercaptopurine (6-MP)]]
+
*[[Mercaptopurine (6-MP)]] 1.5 mg/kg PO twice per day
−
*[[Methotrexate (MTX)]]
+
*[[Methotrexate (MTX)]] by the following age-based criteria:
−
 
+
**Less than 2 years old: 1.25 mg PO once per day
 +
**2 to 10 years old: 2.5 mg PO once per day
 +
**Older than 10 years old: 5 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 
===References===
 
===References===
−
# '''ALGB 01:''' Frei E 3rd, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, Silver RT, Gold GL, Regelson W. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood. 1958 Dec;13(12):1126-48. [http://www.bloodjournal.org/content/13/12/1126.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13596417 PubMed]
+
# '''ALGB 01:''' Frei E 3rd, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, Silver RT, Gold GL, Regelson W. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood. 1958 Dec;13(12):1126-48. [https://doi.org/10.1182/blood.V13.12.1126.1126 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13596417/ PubMed]
−
# '''ALGB 03:''' Frei E, Freireich EJ, Gehan E, Pinkel D, Holland JF, Selawry O, Haurani F, Spurr CL, Hayes DM, James GW, Rothberg H, Sodee DB, Rundles RW, Schroeder LR, Hoogstraten B, Wolman IJ, Traggis DG, Cooper T, Gendel BR, Ebaugh F, Taylor R. Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6-Mercaptopurine and Methotrexate. Blood. 1961;18(4):431-454. [http://www.bloodjournal.org/content/18/4/431.short link to original article]
+
# '''ALGB 03:''' Frei E, Freireich EJ, Gehan E, Pinkel D, Holland JF, Selawry O, Haurani F, Spurr CL, Hayes DM, James GW, Rothberg H, Sodee DB, Rundles RW, Schroeder LR, Hoogstraten B, Wolman IJ, Traggis DG, Cooper T, Gendel BR, Ebaugh F, Taylor R. Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6-Mercaptopurine and Methotrexate. Blood. 1961;18(4):431-454. [https://doi.org/10.1182/blood.V18.4.431.431 link to original article] '''dosing details in manuscript have been reviewed by our editors'''
−
# Frei E 3rd, Karon M, Levin RH, Freireich EJ, Taylor RJ, Hananian J, Selawry O, Holland JF, Hoogstraten B, Wolman IJ, Abir E, Sawitsky A, Lee S, Mills SD, Burgert EO Jr, Spurr CL, Patterson RB, Ebaugh FG, James GW 3rd, Moon JH. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood. 1965 Nov;26(5):642-56. [http://www.bloodjournal.org/content/26/5/642.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/5321112 PubMed]
 
  
−
==Mercaptopurine & Prednisone {{#subobject:f609f5|Regimen=1}}==
+
==Prednisolone monotherapy {{#subobject:5d40b1|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen variant #1 {{#subobject:b66a94|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
−
|}
+
|Not reported
−
===Regimen {{#subobject:c637f6|Variant=1}}===
+
| style="background-color:#91cf61" |Non-randomized
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|Comparator
 
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM196609012750901 Fernbach et al. 1966]
 
−
|style="background-color:#1a9851"|Randomized (C)
 
−
|Cyclophosphamide & Prednisone
 
−
|style="background-color:#ffffbf"|Seems not superior
 
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Mercaptopurine (6-MP)]]
+
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]]
+
*[[Prednisolone (Millipred)]] 50 mg PO once per day on days 1 to 10
−
 
+
'''10-day course'''
−
===References===
+
</div></div><br>
−
# Fernbach DJ, Griffith KM, Haggard ME, Holcomb TM, Sutow WW, Vietti TJ, Windmiller J. Chemotherapy of acute leukemia in childhood: comparison of cyclophosphamide and mercaptopurine. N Engl J Med. 1966 Sep 1;275(9):451-6. [https://www.nejm.org/doi/full/10.1056/NEJM196609012750901 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/5917939 PubMed]
+
<div class="toccolours" style="background-color:#ee6b6e">
−
 
+
===Regimen variant #2 {{#subobject:b6ee94|Variant=1}}===
−
==Prednisolone monotherapy {{#subobject:5d40b1|Regimen=1}}==
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
−
|}
+
|Not reported
−
===Regimen {{#subobject:b66a94|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
 
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Prednisolone (Millipred)]]
+
====Glucocorticoid therapy====
 +
*[[Prednisolone (Millipred)]] 500 mg PO once per day on days 1 to 10
 +
'''10-day course'''
 +
</div></div>
 
===References===
 
===References===
−
# Shanbrom E, Miller S. Critical evaluation of massive steroid therapy of acute leukemia. N Engl J Med. 1962 Jun 28;266:1354-8. [https://www.nejm.org/doi/full/10.1056/NEJM196206282662603 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13911203 PubMed]
+
# Shanbrom E, Miller S. Critical evaluation of massive steroid therapy of acute leukemia. N Engl J Med. 1962 Jun 28;266:1354-8. [https://doi.org/10.1056/NEJM196206282662603 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/13911203/ PubMed]
  
 
==Prednisone monotherapy {{#subobject:5eeb7e|Regimen=1}}==
 
==Prednisone monotherapy {{#subobject:5eeb7e|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen variant #1 {{#subobject:07e67b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.1056/NEJM195807312590502 Granville et al. 1958]
−
|}
+
|1955-1956
−
===Regimen {{#subobject:07e67b|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM195807312590502 Granville et al. 1958]
 
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
−
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
−
*[[Prednisone (Sterapred)]]
+
====Glucocorticoid therapy====
−
===References===
+
*[[Prednisone (Sterapred)]] 125 mg PO twice per day on days 1 to 14, then tapered
−
# Granville NB, Rubio F Jr, Unugur A, Schulman E, Dameshek W. Treatment of acute leukemia in adults with massive doses of prednisone and prednisolone. N Engl J Med. 1958 Jul 31;259(5):207-13. [https://www.nejm.org/doi/full/10.1056/NEJM195807312590502 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13566450 PubMed]
+
'''One course'''
−
 
+
</div></div><br>
−
=Consolidation after upfront therapy=
+
<div class="toccolours" style="background-color:#ee6b6e">
−
==Mercaptopurine & Methotrexate {{#subobject:7a01b3|Regimen=1}}==
+
===Regimen variant #2 {{#subobject:4te67b|Variant=1}}===
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[[#top|back to top]]
+
|[https://doi.org/10.1056/NEJM195807312590502 Granville et al. 1958]
−
|}
+
|1955-1956
−
===Regimen {{#subobject:752310|Variant=1}}===
+
| style="background-color:#91cf61" |Non-randomized
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|Comparator
 
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM198602203140803 Evans et al. 1986]
 
−
|style="background-color:#1a9851"|Randomized (E)
 
−
|WBRT, then 6-MP & MTX (conventional dosing)
 
−
|style="background-color:#d3d3d3"|Not reported
 
 
|-
 
|-
 
|}
 
|}
−
''Note: although this is a randomized trial, the report focuses on this arm, which includes HD-MTX, and not the comparison.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Preceding treatment====
+
====Glucocorticoid therapy====
−
*[[#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-Asparaginase, Vincristine, Prednisone induction]]
+
*[[Prednisone (Sterapred)]] 250 mg PO four times per day on days 1 to 14, then tapered
−
====Chemotherapy====
+
'''One course'''
−
*[[Mercaptopurine (6-MP)]]
+
</div></div>
−
*[[Methotrexate (MTX)]]
 
−
 
 
 
===References===
 
===References===
−
# Evans WE, Crom WR, Abromowitch M, Dodge R, Look AT, Bowman WP, George SL, Pui CH. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia: identification of a relation between concentration and effect. N Engl J Med. 1986 Feb 20;314(8):471-7. [https://www.nejm.org/doi/full/10.1056/NEJM198602203140803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3456079 PubMed]
+
# Granville NB, Rubio F Jr, Unugur A, Schulman E, Dameshek W. Treatment of acute leukemia in adults with massive doses of prednisone and prednisolone. N Engl J Med. 1958 Jul 31;259(5):207-13. [https://doi.org/10.1056/NEJM195807312590502 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/13566450/ PubMed]
  
 
=Late intensification=
 
=Late intensification=
 
==POMP {{#subobject:31219|Regimen=1}}==
 
==POMP {{#subobject:31219|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
POMP: '''<u>P</u>'''urinethol (Mercaptopurine), '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
 
POMP: '''<u>P</u>'''urinethol (Mercaptopurine), '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
 +
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:93b1b3|Variant=1}}===
 
===Regimen {{#subobject:93b1b3|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://jamanetwork.com/journals/jama/fullarticle/344212 Bodey et al. 1976]
+
|[https://doi.org/10.1001/jama.1976.03260360023019 Bodey et al. 1976]
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
|1970-03 to 1973-05
 +
| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts
 
|-
 
|-
 
|}
 
|}
 
''Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.''
 
''Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mercaptopurine (6-MP)]]
+
*[[Mercaptopurine (6-MP)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Vincristine (Oncovin)]]
+
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
−
*[[Methotrexate (MTX)]]
+
*[[Methotrexate (MTX)]] 7.5 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
*[[Prednisone (Sterapred)]]
+
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 +
'''One course'''
 +
</div></div>
 
===References===
 
===References===
−
# Bodey GP, Freireich EJ, Gehan E, McCredie KB, Rodriguez V, Gutterman J, Burgess MA. Late intensification therapy for acute leukemia in remission: chemotherapy and immunotherapy. JAMA. 1976 Mar 8;235(10):1021-5. [https://jamanetwork.com/journals/jama/fullarticle/344212 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/946184 PubMed]
+
# Bodey GP, Freireich EJ, Gehan E, McCredie KB, Rodriguez V, Gutterman J, Burgess MA. Late intensification therapy for acute leukemia in remission: chemotherapy and immunotherapy. JAMA. 1976 Mar 8;235(10):1021-5. [https://doi.org/10.1001/jama.1976.03260360023019 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/946184/ PubMed]
−
 
 
−
=Maintenance after upfront therapy=
 
−
==Methotrexate monotherapy {{#subobject:478e97|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:028121|Variant=1}}===
 
−
{| class="wikitable" style="width: 100%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|Comparator
 
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/656675 Selawry & Holland 1965 (ALGB 6313)]
 
−
|style="background-color:#1a9851"|Randomized (E)
 
−
|PO MTX
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/343520 Burgert et al. 1969 (ALGB 6311)]
 
−
|style="background-color:#1a9851"|Randomized (E)
 
−
|PO MTX
 
−
| style="background-color:#ffffbf" |Seems not superior
 
−
|-
 
−
|}
 
−
====Preceding treatment====
 
−
*Vincristine & Prednisone induction
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] IV or IM
 
−
 
 
−
===References===
 
−
# '''ALGB 6313:''' Selawry OS, Holland JF; Acute Leukemia Group B. New treatment schedule with improved survival in childhood leukemia: intermittent parenteral vs daily oral administration of methotrexate for maintenance of induced remission. JAMA. 1965 Oct 4;194(1):75-81. [https://jamanetwork.com/journals/jama/article-abstract/656675 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/5896942 PubMed]
 
−
# '''ALGB 6311:''' Burgert EO, Valvo F, Petzold G, Holland JF; Acute Leukemia Group B. Acute lymphocytic leukemia in children: maintenance therapy with methotrexat administered intermittently. JAMA. 1969 Feb 3;207(5):923-8. [https://jamanetwork.com/journals/jama/article-abstract/343520 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/4303512 PubMed]
 
  
 
=Relapsed or refractory=
 
=Relapsed or refractory=
−
==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e05416|Regimen=1}}==
+
==BCG vaccine monotherapy {{#subobject:e05416|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:637e03|Variant=1}}===
 
===Regimen {{#subobject:637e03|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.sciencedirect.com/science/article/pii/S0140673669926488 Mathé et al. 1969]
+
|[https://doi.org/10.1016/s0140-6736(69)92648-8 Mathé et al. 1969]
 +
|Not reported
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[Bacillus Calmette-Guérin (BCG)]]
+
*[[BCG vaccine]]
−
===References===
+
</div></div>
−
# Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697-9. [https://www.sciencedirect.com/science/article/pii/S0140673669926488 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/4182654 PubMed]
 
−
 
 
−
==Cyclophosphamide monotherapy {{#subobject:cd166d|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:047e6a|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/331608 Fernbach et al. 1962]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
===References===
 
−
# Fernbach DJ, Sutow WW, Thurman WG, Vietti TJ. Clinical evaluation of cyclophosphamide: a new agent for the treatment of children with acute leukemia. JAMA. 1962 Oct 6;182:30-7. [https://jamanetwork.com/journals/jama/article-abstract/331608 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13892445 PubMed]
 
−
 
 
−
==Daunorubicin & Prednisone {{#subobject:aa10e0|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen {{#subobject:19d9c6|Variant=1}}===
 
−
{| class="wikitable" style="width: 50%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM196901232800401 Holton et al. 1969]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]]
 
−
*[[Prednisone (Sterapred)]]
 
 
===References===
 
===References===
−
# Holton CP, Vietti TJ, Nora AH, Donaldson MH, Stuckey WJ Jr, Watkins WL, Lane DM. Clinical study of daunomycin and prednisone for induction of remission in children with advanced leukemia. N Engl J Med. 1969 Jan 23;280(4):171-4. [https://www.nejm.org/doi/full/10.1056/NEJM196901232800401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/5248383 PubMed]
+
# Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697-9. [https://doi.org/10.1016/s0140-6736(69)92648-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4182654/ PubMed]
  
 
==Pentostatin monotherapy {{#subobject:aa19e0|Regimen=1}}==
 
==Pentostatin monotherapy {{#subobject:aa19e0|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:19d2c6|Variant=1}}===
 
===Regimen {{#subobject:19d2c6|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(81)91491-4/fulltext Prentice et al. 1981]
+
|[https://doi.org/10.1016/S0140-6736(81)91491-4 Prentice et al. 1981]
 +
|Not reported
 
| style="background-color:#ffffbe" |Pilot
 
| style="background-color:#ffffbe" |Pilot
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Pentostatin (Nipent)]]
 
*[[Pentostatin (Nipent)]]
 +
</div></div>
 
===References===
 
===References===
−
# Prentice HG, Russell NH, Lee N, Ganeshaguru K, Blacklock H, Piga A, Smyth JF, Hoffbrand AV. Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia. Lancet. 1981 Dec 5;2(8258):1250-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(81)91491-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6118669 PubMed]
+
# Prentice HG, Russell NH, Lee N, Ganeshaguru K, Blacklock H, Piga A, Smyth JF, Hoffbrand AV. Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia. Lancet. 1981 Dec 5;2(8258):1250-4. [https://doi.org/10.1016/S0140-6736(81)91491-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6118669/ PubMed]
−
 
 
 
==TBI, then auto HSCT {{#subobject:1a2735|Regimen=1}}==
 
==TBI, then auto HSCT {{#subobject:1a2735|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
TBI: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 +
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:635694|Variant=1}}===
 
===Regimen {{#subobject:635694|Variant=1}}===
−
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJM195904022601401 McGovern et al. 1959]
+
|[https://doi.org/10.1056/NEJM195904022601401 McGovern et al. 1959]
 
| style="background-color:#ffffbe" |Pilot
 
| style="background-color:#ffffbe" |Pilot
 
|-
 
|-
 
|}
 
|}
−
''This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.''
+
''Note: This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Radiotherapy====
 
====Radiotherapy====
 
*[[External_beam_radiotherapy|Total body irradiation]]
 
*[[External_beam_radiotherapy|Total body irradiation]]
 +
</div></div>
 +
===References===
 +
# McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. [https://doi.org/10.1056/NEJM195904022601401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13644566/ PubMed]
 +
==Vincristine liposomal monotherapy {{#subobject:f19406|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:18f662|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|Dates of enrollment
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979201/ O'Brien et al. 2012 (RALLY)]
 +
|2007 to not reported
 +
|style="background-color:#91cf61"|Phase 2 (RT)
 +
|ORR: 35%
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Vincristine liposomal (Marqibo)]] 2.25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
'''7-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. [https://www.nejm.org/doi/full/10.1056/NEJM195904022601401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13644566 PubMed]
+
# '''RALLY:''' O'Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, Ben-Yehuda D, Stock W, Coutre S, Douer D, Heffner LT, Larson M, Seiter K, Smith S, Assouline S, Kuriakose P, Maness L, Nagler A, Rowe J, Schaich M, Shpilberg O, Yee K, Schmieder G, Silverman JA, Thomas D, Deitcher SR, Kantarjian H. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013 Feb 20;31(6):676-83. Epub 2012 Nov 19. [https://doi.org/10.1200/jco.2012.46.2309 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979201/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169518/ PubMed] [https://clinicaltrials.gov/study/NCT00495079 NCT00495079]
−
 
 
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Acute leukemias]]
+
[[Category:Acute lymphoblastic leukemias]]
−
[[Category:Pediatric cancers]]
+
[[Category:Pediatric hematologic neoplasms]]

Latest revision as of 12:17, 15 July 2024

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main B-ALL page for current regimens.

11 regimens on this page
13 variants on this page


Upfront induction therapy

Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone

Regimen

Study Dates of enrollment Evidence
Takeuchi et al. 2002 (JALSG-ALL93) 1993-1997 Non-randomized

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • G-CSF 200 mcg/m2 IV once per day on days 12 to 26

35-day course

Subsequent treatment

  • Consolidation I (see paper for details)

References

  1. JALSG-ALL93: Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002 Jul;16(7):1259-66. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hunault et al. 2004 (GOELAL02) 1994-1998 Phase 3 (C) Idarubicin, L-asparaginase, Vincristine, Prednisone; oral prednisone Did not meet primary endpoint of response rate

Note: This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

Glucocorticoid therapy

35-day course

References

  1. GOELAL02: Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, Lamy T, Pignon B, Jouet JP, Garidi R, Caillot D, Berthou C, Guyotat D, Sadoun A, Sotto JJ, Lioure B, Casassus P, Solal-Celigny P, Stalnikiewicz L, Audhuy B, Blanchet O, Baranger L, Béné MC, Ifrah N; GOELAMS (Groupe Ouest-Est des Leucémies Airguës et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004 Nov 15;104(10):3028-37. Epub 2004 Jul 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00483132

L-Asparaginase, Vincristine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Henderson et al. 1979 (CALGB 7113) 1971-1976 Non-randomized
Gottlieb et al. 1984 (CALGB 7612) 1976-1980 Randomized (C) DOLP Inferior CR rate

Note: The asparaginase dosing shown here was that after a mid-protocol amendment due to excess toxicity.

Chemotherapy

Glucocorticoid therapy

28-day course

References

  1. CALGB 7113: Henderson ES, Scharlau C, Cooper MR, Haurani FI, Silver RT, Brunner K, Carey RW, Falkson G, Blom J, Nawabi IV, Levine AS, Bank A, Cuttner J, Cornwell GG 3rd, Henry P, Nissen NI, Wiernik PH, Leone L, Wohl H, Rai K, James GW, Weinberg V, Glidewell O, Holland JF. Combination chemotherapy and radiotherapy for acute lymphocytic leukemia in adults: results of CALGB protocol 7113. Leuk Res. 1979;3(6):395-407. link to original article dosing details in manuscript have been reviewed by our editors PubMed
  2. CALGB 7612: Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN, Hutchinson JL, Raich P, Cooper MR, Wiernik P, Anderson JR, Holland JF. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984 Jul;64(1):267-74. link to original article PubMed

Mercaptopurine & Methotrexate

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Frei et al. 1958 (ALGB 01) Not reported Randomized (E-switch-ic) 6-MP & MTX; alternate dosing Did not meet endpoints
Frei et al. 1961 (ALGB 03) 1957-1960 Randomized (E-esc) 1. 6-MP
2. MTX 		Did not meet endpoint of DOR

Note: this is one of the first combination regimens in hematology/oncology.

Chemotherapy

  • Mercaptopurine (6-MP) 1.5 mg/kg PO twice per day
  • Methotrexate (MTX) by the following age-based criteria:
    • Less than 2 years old: 1.25 mg PO once per day
    • 2 to 10 years old: 2.5 mg PO once per day
    • Older than 10 years old: 5 mg PO once per day

Continued indefinitely

References

  1. ALGB 01: Frei E 3rd, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, Silver RT, Gold GL, Regelson W. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood. 1958 Dec;13(12):1126-48. link to original article PubMed
  2. ALGB 03: Frei E, Freireich EJ, Gehan E, Pinkel D, Holland JF, Selawry O, Haurani F, Spurr CL, Hayes DM, James GW, Rothberg H, Sodee DB, Rundles RW, Schroeder LR, Hoogstraten B, Wolman IJ, Traggis DG, Cooper T, Gendel BR, Ebaugh F, Taylor R. Studies of Sequential and Combination Antimetabolite Therapy in Acute Leukemia: 6-Mercaptopurine and Methotrexate. Blood. 1961;18(4):431-454. link to original article dosing details in manuscript have been reviewed by our editors

Prednisolone monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Shanbrom & Miller 1962 Not reported Non-randomized

Glucocorticoid therapy

10-day course


Regimen variant #2

Study Dates of enrollment Evidence
Shanbrom & Miller 1962 Not reported Non-randomized

Glucocorticoid therapy

10-day course

References

  1. Shanbrom E, Miller S. Critical evaluation of massive steroid therapy of acute leukemia. N Engl J Med. 1962 Jun 28;266:1354-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Prednisone monotherapy

Regimen variant #1

Study Dates of enrollment Evidence
Granville et al. 1958 1955-1956 Non-randomized

Glucocorticoid therapy

One course


Regimen variant #2

Study Dates of enrollment Evidence
Granville et al. 1958 1955-1956 Non-randomized

Glucocorticoid therapy

One course

References

  1. Granville NB, Rubio F Jr, Unugur A, Schulman E, Dameshek W. Treatment of acute leukemia in adults with massive doses of prednisone and prednisolone. N Engl J Med. 1958 Jul 31;259(5):207-13. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Late intensification

POMP

POMP: Purinethol (Mercaptopurine), Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study Dates of enrollment Evidence
Bodey et al. 1976 1970-03 to 1973-05 Non-randomized, fewer than 20 pts

Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.

Chemotherapy

Glucocorticoid therapy

One course

References

  1. Bodey GP, Freireich EJ, Gehan E, McCredie KB, Rodriguez V, Gutterman J, Burgess MA. Late intensification therapy for acute leukemia in remission: chemotherapy and immunotherapy. JAMA. 1976 Mar 8;235(10):1021-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Relapsed or refractory

BCG vaccine monotherapy

Regimen

Study Dates of enrollment Evidence
Mathé et al. 1969 Not reported Non-randomized

Immunotherapy

References

  1. Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, De Vassal F. Active immunotherapy for acute lymphoblastic leukaemia. Lancet. 1969 Apr 5;1(7597):697-9. link to original article PubMed

Pentostatin monotherapy

Regimen

Study Dates of enrollment Evidence
Prentice et al. 1981 Not reported Pilot

Chemotherapy

References

  1. Prentice HG, Russell NH, Lee N, Ganeshaguru K, Blacklock H, Piga A, Smyth JF, Hoffbrand AV. Therapeutic selectivity of and predication of response to 2'-deoxycoformycin in acute leukaemia. Lancet. 1981 Dec 5;2(8258):1250-4. link to original article PubMed

TBI, then auto HSCT

TBI: Total Body Irradiation

Regimen

Study Evidence
McGovern et al. 1959 Pilot

Note: This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.

Radiotherapy

References

  1. McGovern JJ Jr, Russell PS, Atkins L, Webster EW. Treatment of terminal leukemic relapse by total-body irradiation and intravenous infusion of stored autologous bone marrow obtained during remission. N Engl J Med. 1959 Apr 2;260(14):675-83. link to original article PubMed

Vincristine liposomal monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
O'Brien et al. 2012 (RALLY) 2007 to not reported Phase 2 (RT) ORR: 35%

Chemotherapy

7-day cycles

References

  1. RALLY: O'Brien S, Schiller G, Lister J, Damon L, Goldberg S, Aulitzky W, Ben-Yehuda D, Stock W, Coutre S, Douer D, Heffner LT, Larson M, Seiter K, Smith S, Assouline S, Kuriakose P, Maness L, Nagler A, Rowe J, Schaich M, Shpilberg O, Yee K, Schmieder G, Silverman JA, Thomas D, Deitcher SR, Kantarjian H. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013 Feb 20;31(6):676-83. Epub 2012 Nov 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00495079
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