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

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=Upfront induction therapy=
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<br>'''This is a placeholder for now; we'll be moving regimens here soon.'''
+
==Aminopterin monotherapy {{#subobject:1cf0b5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:be57ed|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM194806032382301 Farber et al. 1948]
 +
|1947-1948
 +
| style="background-color:#ffffbe" |Non-randomized pilot
 +
|-
 +
|}
 +
''Note: This regimen is 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.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Aminopterin]]
 +
</div></div>
 +
===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://doi.org/10.1056/NEJM194806032382301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18860765 PubMed]
 +
==COMP {{#subobject:2ec876|Regimen=1}}==
 +
COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:0ecc0a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM198303103081003 Anderson et al. 1983]
 +
|1977-1979
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|Modified LSA<sub>2</sub>-L<sub>2</sub>
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Vincristine (Oncovin)]]
 +
*[[Methotrexate (MTX)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
</div></div>
 +
===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://doi.org/10.1056/NEJM198303103081003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6338381 PubMed]
 +
==Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone {{#subobject:5a7eda|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:245098|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(07)61126-x Pieters et al. 2007 (Interfant-99)]
 +
|1999-2005
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[B-cell_acute_lymphoblastic_leukemia#Prednisone_monotherapy|Prednisone pre-phase]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cytarabine (Ara-C)]]
 +
*[[Daunorubicin (Cerubidine)]]
 +
*[[Asparaginase (Elspar)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Dexamethasone (Decadron)]]
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*MARAM consolidation
 +
</div></div>
 +
===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://doi.org/10.1016/s0140-6736(07)61126-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/17658395 PubMed] NCT00015873
 +
==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone {{#subobject:177f43|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:2c8cee|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/0140-6736(91)90733-6 Rivera et al. 1991]
 +
|NR in abstract
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
|-
 +
|[https://doi.org/10.1056/NEJM199802193380803 Evans et al. 1998]
 +
|1988-1991
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cytarabine (Ara-C)]]
 +
*[[Daunorubicin (Cerubidine)]]
 +
*[[Asparaginase (Elspar)]]
 +
*[[Teniposide (Vumon)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*High-dose MTX
 +
</div></div>
 +
===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://doi.org/10.1016/0140-6736(91)90733-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1670723 PubMed]
 +
# 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://doi.org/10.1056/NEJM199802193380803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9468466 PubMed]
 +
==Daunorubicin, Vincristine, Prednisone {{#subobject:h1huh5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:h1cc9b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1002/1097-0142(197402)33:2%3C545::aid-cncr2820330233%3E3.0.co;2-m Halazun et al. 1974 (ALGB 6801)]
 +
|1968-1971
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[#Vincristine_.26_Prednisone|Vincristine & Prednisone]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Daunorubicin (Cerubidine)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
</div></div>
 +
===References===
 +
#Mathé G, Hayat M, Schwarzenberg L, Amiel JL, Schneider M, Cattan A, Schlumberger JR, Jasmin C. Acute lymphoblastic leukaemia treated with a combination of prednisone, vincristine, and rubidomycin: Value of pathogen-free rooms. Lancet. 1967 Aug 19;2(7512):380-2. [https://doi.org/10.1016/s0140-6736(67)92004-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4166329/ PubMed]
 +
#'''ALGB 6801:''' Halazun JF, Wagner HR, Gaeta JF, Sinks LF. Proceedings: Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia. Cancer. 1974 Feb;33(2):545-54. [https://doi.org/10.1002/1097-0142(197402)33:2%3C545::aid-cncr2820330233%3E3.0.co;2-m link to original article] [https://pubmed.ncbi.nlm.nih.gov/4521474/ PubMed]
 +
==Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Prednisone {{#subobject:h1h91c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:hbn19b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3595424/ Vrooman et al. 2013 (DFCI 00-01)]
 +
|2000-2004
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 trial
 +
|-
 +
|}
 +
''Note: the MTX dose reported in the manuscript appears to be erroneous, but is replicated here.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
 +
*[[Methotrexate (MTX)]] 4 mg/m<sup>2</sup> IV once, '''given 8 to 24 hours after doxorubicin'''
 +
*[[Asparaginase (Elspar)]] 25,000 units/m<sup>2</sup> IM once (day not specified)
 +
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 0, 7, 14, 21
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day IV or PO on days 0 to 28
 +
====Supportive therapy====
 +
*High-risk patients: [[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0 & 1
 +
'''29-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Intensification
 +
</div></div>
 +
===References===
 +
#'''DFCI 00-01:''' Vrooman LM, Stevenson KE, Supko JG, O'Brien J, Dahlberg SE, Asselin BL, Athale UH, Clavell LA, Kelly KM, Kutok JL, Laverdière C, Lipshultz SE, Michon B, Schorin M, Relling MV, Cohen HJ, Neuberg DS, Sallan SE, Silverman LB. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013 Mar 20;31(9):1202-10. Epub 2013 Jan 28. [https://doi.org/10.1200/jco.2012.43.2070 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3595424/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23358966/ PubMed] NCT00165178
 +
==Doxorubicin, Methotrexate, Vincristine, Prednisone {{#subobject:96590c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:dee4bf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM198609113151101 Clavell et al. 1986]
 +
|1981-1985
 +
| style="background-color:#91cf61" |Non-randomized
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Methotrexate (MTX)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
</div></div>
 +
===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://doi.org/10.1056/NEJM198609113151101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2943992 PubMed]
 +
==L-Asparaginase, Vincristine, Dexamethasone {{#subobject:54ea09|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4c9de2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1996.14.3.911 Veerman et al. 1996 (DCOG ALL-VI)]
 +
|1984-1988
 +
| 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)]
 +
|1993-1995
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-asparaginase, Vincristine, Prednisone]]
 +
|style="background-color:#1a9850"|Superior EFS
 +
|-
 +
|[https://doi.org/10.1111/j.1365-2141.2005.05509.x Mitchell et al. 2005 (UK MRC ALL97)]
 +
|1997-2002
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisolone|L-asparaginase, Vincristine, Prednisolone]]
 +
|style="background-color:#1a9850"|Superior EFS
 +
|-
 +
|[https://doi.org/10.1016/s1470-2045(09)70228-1 Veerman et al. 2009 (DCOG ALL-9)]
 +
|1997-2004
 +
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Asparaginase (Elspar)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Dexamethasone (Decadron)]]
 +
</div></div>
 +
===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; Dutch Childhood Oncology Group. 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://doi.org/10.1200/JCO.1996.14.3.911 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622039 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://pubmed.ncbi.nlm.nih.gov/12531809 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://doi.org/10.1111/j.1365-2141.2005.05509.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15952999 PubMed] NCT00003437
 +
## '''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://doi.org/10.1016/s0140-6736(06)69558-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1016/s1470-2045(09)70228-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19747876 PubMed] NTR460
 +
==L-Asparaginase, Vincristine, Prednisolone {{#subobject:65692a|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4af0d5|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1038/sj.leu.2401704 Hann et al. 2000 (MRC UKALL XI)]
 +
|1990-1997
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1111/j.1365-2141.2005.05509.x Mitchell et al. 2005 (UK MRC ALL97)]
 +
|1997-2002
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
 +
|style="background-color:#d73027"|Inferior EFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Asparaginase (Elspar)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisolone (Millipred)]]
 +
</div></div>
 +
===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://doi.org/10.1038/sj.leu.2401704 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1111/j.1365-2141.2005.05509.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/15952999 PubMed] NCT00003437
 +
## '''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://doi.org/10.1016/s0140-6736(06)69558-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17046466 PubMed]
 +
==L-Asparaginase, Vincristine, Prednisone {{#subobject:d039d8|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a4174a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://cancerres.aacrjournals.org/content/37/2/535.long Ortega et al. 1977 (CCG 101/143)]
 +
|1971-NR
 +
| style="background-color:#91cf61" |Non-randomized (RT)
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://pubmed.ncbi.nlm.nih.gov/2665546 van der Does-van den Berg et al. 1989 (DCLSG ALL V)]
 +
|1979-1982
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1111/j.1365-2141.1991.tb04415.x Eden et al. 1991 (MRC UKALL VIII)]
 +
|1979-1982
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.1993.11.3.527 Tubergen et al. 1993 (CCG-105)]
 +
|1983-1989
 +
|style="background-color:#1a9851"|Phase 3 (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)]
 +
|1993-1995
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
 +
|style="background-color:#d73027"|Inferior EFS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1895867/ Matloub et al. 2006 (CCG-1952)]
 +
|1996-2000
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Asparaginase (Elspar)]]
 +
*[[Vincristine (Oncovin)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
'''28-day course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*CCC-1952: Consolidation
 +
</div></div>
 +
===References===
 +
# '''CCG 101/143:''' Ortega JA, Nesbit ME Jr, Donaldson MH, Hittle RE, Weiner J, Karon M, Hammond D. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res. 1977 Feb;37(2):535-40. [https://cancerres.aacrjournals.org/content/37/2/535.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/264412 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; Dutch Childhood Leukemia Study Group. 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://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1111/j.1365-2141.1991.tb04415.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1200/JCO.1993.11.3.527 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://pubmed.ncbi.nlm.nih.gov/12531809 PubMed]
 +
# '''CCG-1952:''' Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children's Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. Blood. 2006 Aug 15;108(4):1165-73. Epub 2006 Apr 11. [https://doi.org/10.1182/blood-2005-12-011809 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1895867/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16609069/ PubMed] NCT00002744
 +
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1fc958|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!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)]
 +
|NR
 +
|style="background-color:#1a9851"|Randomized (E-switch-ic)
 +
|[[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]; alternate dosing
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1182/blood.V18.4.431.431 Frei et al. 1961 (ALGB 03)]
 +
|1957-1960
 +
|style="background-color:#1a9851"|Randomized (E-esc)
 +
|1. [[#Mercaptopurine_monotherapy_88|6-MP]]<br>2. [[#Methotrexate_monotherapy_88|MTX]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[http://www.bloodjournal.org/content/26/5/642.long Frei et al. 1965]
 +
|NR
 +
| 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.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Mercaptopurine (6-MP)]]
 +
*[[Methotrexate (MTX)]]
 +
</div></div>
 +
===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://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. [https://doi.org/10.1182/blood.V18.4.431.431 link to original article]
 +
# 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://pubmed.ncbi.nlm.nih.gov/5321112 PubMed]
 +
==Mercaptopurine & Prednisone {{#subobject:f609f5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c637f6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM196609012750901 Fernbach et al. 1966]
 +
|1960-1962
 +
|style="background-color:#1a9851"|Randomized (C)
 +
|[[#Cyclophosphamide_.26_Prednisone_99|Cyclophosphamide & Prednisone]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Mercaptopurine (6-MP)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 +
</div></div>
 +
===References===
 +
# 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://doi.org/10.1056/NEJM196609012750901 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5917939 PubMed]
  
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]

Revision as of 01:34, 9 February 2023

Back to Top

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 NCCN Guidelines. Is there a regimen missing from this list? See the main pediatric B-ALL page for current regimens.

17 regimens on this page
17 variants on this page


Upfront induction therapy

Aminopterin monotherapy

Regimen

Study Years of enrollment Evidence
Farber et al. 1948 1947-1948 Non-randomized pilot

Note: This regimen is 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 published in Science in 1947). This agent is no longer available but was used clinically for several decades.

Chemotherapy

References

  1. 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. link to original article PubMed

COMP

COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Anderson et al. 1983 1977-1979 Phase 3 (E-de-esc) Modified LSA2-L2 Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. 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. link to original article PubMed

Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone

Regimen

Study Years of enrollment Evidence
Pieters et al. 2007 (Interfant-99) 1999-2005 Non-randomized portion of RCT

Preceding treatment

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

  • MARAM consolidation

References

  1. 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. link to original article PubMed NCT00015873

Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone

Regimen

Study Years of enrollment Evidence
Rivera et al. 1991 NR in abstract Non-randomized portion of RCT
Evans et al. 1998 1988-1991 Non-randomized portion of RCT

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

  • High-dose MTX

References

  1. 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. link to original article PubMed
  2. 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. link to original article PubMed

Daunorubicin, Vincristine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Halazun et al. 1974 (ALGB 6801) 1968-1971 Phase 3 (E-RT-esc) Vincristine & Prednisone Did not meet primary endpoint of CR rate

Chemotherapy

Glucocorticoid therapy

References

  1. Mathé G, Hayat M, Schwarzenberg L, Amiel JL, Schneider M, Cattan A, Schlumberger JR, Jasmin C. Acute lymphoblastic leukaemia treated with a combination of prednisone, vincristine, and rubidomycin: Value of pathogen-free rooms. Lancet. 1967 Aug 19;2(7512):380-2. link to original article PubMed
  2. ALGB 6801: Halazun JF, Wagner HR, Gaeta JF, Sinks LF. Proceedings: Daunorubicin cardiac toxicity in children with acute lymphocytic leukemia. Cancer. 1974 Feb;33(2):545-54. link to original article PubMed

Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Prednisone

Regimen

Study Years of enrollment Evidence
Vrooman et al. 2013 (DFCI 00-01) 2000-2004 Non-randomized portion of phase 3 trial

Note: the MTX dose reported in the manuscript appears to be erroneous, but is replicated here.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

29-day course

Subsequent treatment

  • Intensification

References

  1. DFCI 00-01: Vrooman LM, Stevenson KE, Supko JG, O'Brien J, Dahlberg SE, Asselin BL, Athale UH, Clavell LA, Kelly KM, Kutok JL, Laverdière C, Lipshultz SE, Michon B, Schorin M, Relling MV, Cohen HJ, Neuberg DS, Sallan SE, Silverman LB. Postinduction dexamethasone and individualized dosing of Escherichia Coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study--Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013 Mar 20;31(9):1202-10. Epub 2013 Jan 28. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00165178

Doxorubicin, Methotrexate, Vincristine, Prednisone

Regimen

Study Years of enrollment Evidence
Clavell et al. 1986 1981-1985 Non-randomized

Chemotherapy

Glucocorticoid therapy

References

  1. 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. link to original article PubMed

L-Asparaginase, Vincristine, Dexamethasone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Veerman et al. 1996 (DCOG ALL-VI) 1984-1988 Non-randomized
Bostrom et al. 2003 (CCG-1922) 1993-1995 Phase 3 (E-switch-ic) L-asparaginase, Vincristine, Prednisone Superior EFS
Mitchell et al. 2005 (UK MRC ALL97) 1997-2002 Phase 3 (E-switch-ic) L-asparaginase, Vincristine, Prednisolone Superior EFS
Veerman et al. 2009 (DCOG ALL-9) 1997-2004 Non-randomized

Chemotherapy

Glucocorticoid therapy

References

  1. 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; Dutch Childhood Oncology Group. 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. link to original article PubMed
  2. 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. link to original article PubMed
  3. 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. link to original article PubMed NCT00003437
    1. 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. link to original article PubMed
  4. 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. link to original article PubMed NTR460

L-Asparaginase, Vincristine, Prednisolone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hann et al. 2000 (MRC UKALL XI) 1990-1997 Non-randomized portion of RCT
Mitchell et al. 2005 (UK MRC ALL97) 1997-2002 Phase 3 (C) L-asparaginase, Vincristine, Dexamethasone Inferior EFS

Chemotherapy

Glucocorticoid therapy

References

  1. 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. link to original article PubMed
  2. 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. link to original article PubMed NCT00003437
    1. 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. link to original article PubMed

L-Asparaginase, Vincristine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ortega et al. 1977 (CCG 101/143) 1971-NR Non-randomized (RT)
van der Does-van den Berg et al. 1989 (DCLSG ALL V) 1979-1982 Phase 3 (C) DOLP Seems not superior
Eden et al. 1991 (MRC UKALL VIII) 1979-1982 Phase 3 (C) DOLP Seems not superior
Tubergen et al. 1993 (CCG-105) 1983-1989 Phase 3 (C) DOLP Not reported
Bostrom et al. 2003 (CCG-1922) 1993-1995 Phase 3 (C) L-asparaginase, Vincristine, Dexamethasone Inferior EFS
Matloub et al. 2006 (CCG-1952) 1996-2000 Non-randomized portion of phase 3 RCT

Chemotherapy

Glucocorticoid therapy

28-day course

Subsequent treatment

  • CCC-1952: Consolidation

References

  1. CCG 101/143: Ortega JA, Nesbit ME Jr, Donaldson MH, Hittle RE, Weiner J, Karon M, Hammond D. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res. 1977 Feb;37(2):535-40. link to original article PubMed
  2. 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; Dutch Childhood Leukemia Study Group. 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. PubMed
  3. 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. link to original article PubMed
  4. 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. link to original article PubMed
  5. 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. link to original article PubMed
  6. CCG-1952: Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children's Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. Blood. 2006 Aug 15;108(4):1165-73. Epub 2006 Apr 11. link to original article link to PMC article PubMed NCT00002744

Mercaptopurine & Methotrexate

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Frei et al. 1958 (ALGB 01) NR Randomized (E-switch-ic) 6-MP & MTX; alternate dosing Seems not superior
Frei et al. 1961 (ALGB 03) 1957-1960 Randomized (E-esc) 1. 6-MP
2. MTX 		Seems not superior
Frei et al. 1965 NR Non-randomized

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

Chemotherapy

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
  3. 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. link to original article PubMed

Mercaptopurine & Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fernbach et al. 1966 1960-1962 Randomized (C) Cyclophosphamide & Prednisone Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. 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. link to original article PubMed
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