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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 29
Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 1 to 3, 8 to 10
L-Asparaginase 6000 IU/m² IV once per day on days 29 to 35
Vincristine (Oncovin) 1.3 mg/m² (maximum dose of 2 mg) IV bolus once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Prednisolone (Millipred) 40 mg/m² PO once per day on days 1 to 10

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

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

Idarubicin (Idamycin) 5 mg/m² IV once per day on days 1, 8, 15, 22
Asparaginase (Elspar) 7500 IU/m² IV once per day on days 10, 13, 16, 19, 22, 25
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15, 22

Glucocorticoid therapy

Prednisone (Sterapred) 40 mg/m² PO or IV once per day on days 1 to 21

35-day course

References

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

Asparaginase (Elspar) 500 IU/kg IV once per day on days 16 to 25
Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15

Glucocorticoid therapy

Prednisone (Sterapred) 40 mg/m²/day PO on days 1 to 21, then tapered off over days 22 to 28

28-day course

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. link to original article dosing details in manuscript have been reviewed by our editors 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. 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

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
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

Prednisolone (Millipred) 50 mg PO once per day on days 1 to 10

10-day course

Regimen variant #2

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

Glucocorticoid therapy

Prednisolone (Millipred) 500 mg PO once per day on days 1 to 10

10-day course

References

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

Prednisone (Sterapred) 125 mg PO twice per day on days 1 to 14, then tapered

One course

Regimen variant #2

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

Glucocorticoid therapy

Prednisone (Sterapred) 250 mg PO four times per day on days 1 to 14, then tapered

One course

References

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

Mercaptopurine (6-MP) 500 mg/m² IV once per day on days 1 to 5
Vincristine (Oncovin) 2 mg IV once on day 1
Methotrexate (MTX) 7.5 mg/m² IV once per day on days 1 to 5

Glucocorticoid therapy

Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

One course

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. 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

BCG vaccine

References

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

Pentostatin (Nipent)

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. 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

Total body irradiation

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. 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

Vincristine liposomal (Marqibo) 2.25 mg/m² IV over 60 minutes once on day 1

7-day cycles

References

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

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-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.
+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.
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
-|<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>
+|<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>
-<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>
+<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>
 |}
 {{TOC limit|limit=3}}
 =Upfront induction therapy=
-==Aminopterin monotherapy {{#subobject:1cf0b5|Regimen=1}}==
+==Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
-===Regimen {{#subobject:be57ed|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.nejm.org/doi/10.1056/NEJM194806032382301 Farber et al. 1948]
-| style="background-color:#ffffbe" |Non-randomized pilot
-|-
-|}
-''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.''
-====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://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
-===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://www.nejm.org/doi/full/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
-|-
-|}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Vincristine (Oncovin)]]
-*[[Methotrexate (MTX)]]
-====Glucocorticoid therapy====
-*[[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://pubmed.ncbi.nlm.nih.gov/6338381 PubMed]
-==Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
 ===Regimen {{#subobject:0f2246|Variant=1}}===
 {| class="wikitable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 72: / Line 24: @@
 |-
 |}
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Asparaginase (Elspar)|L-Asparaginase]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[Prednisolone (Millipred)]]
-===References===
-# '''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] [https://pubmed.ncbi.nlm.nih.gov/12094249 PubMed]
-==Cytarabine, Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone {{#subobject:5a7eda|Regimen=1}}==
-===Regimen {{#subobject:245098|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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
-|-
-|}
-====Preceding treatment====
-*Prednisone pre-phase
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]]
-*[[Daunorubicin (Cerubidine)]]
-*[[Asparaginase (Elspar)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[Dexamethasone (Decadron)]]
-====Subsequent treatment====
-*MARAM consolidation
-===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://pubmed.ncbi.nlm.nih.gov/17658395 PubMed] NCT00015873
-==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone {{#subobject:177f43|Regimen=1}}==
-===Regimen {{#subobject:2c8cee|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[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]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-====Chemotherapy====
-*[[Cytarabine (Ara-C)]]
-*[[Daunorubicin (Cerubidine)]]
-*[[Asparaginase (Elspar)]]
-*[[Teniposide (Vumon)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
-====Subsequent treatment====
-*High-dose MTX
-===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://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://www.nejm.org/doi/full/10.1056/NEJM199802193380803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9468466 PubMed]
-==Daunorubicin, Vincristine, Prednisone {{#subobject:h1huh5|Regimen=1}}==
-===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
-|-
-|}
-====Chemotherapy====
-*[[Daunorubicin (Cerubidine)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
-===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}}==
-===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.''
 ====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 29
-*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
+*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 3, 8 to 10
-*[[Methotrexate (MTX)]] 4 mg/m<sup>2</sup> IV once, '''given 8 to 24 hours after doxorubicin'''
+*[[Asparaginase (Elspar)|L-Asparaginase]] 6000 IU/m<sup>2</sup> IV once per day on days 29 to 35
-*[[Asparaginase (Elspar)]] 25,000 units/m<sup>2</sup> IM once (day not specified)
+*[[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
-*[[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
+*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 10
+====Supportive therapy====
-====Supportive medications====
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 200 mcg/m<sup>2</sup> IV once per day on days 12 to 26
+'''35-day course'''
-*High-risk patients: [[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0 & 1
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
-'''29-day course'''
 ====Subsequent treatment====
+*Consolidation I (see paper for details)
-*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}}==
-===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://www.nejm.org/doi/full/10.1056/NEJM198609113151101 Clavell et al. 1986]
-|1981-1985
-| style="background-color:#91cf61" |Non-randomized
-|-
-|}
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
-*[[Methotrexate (MTX)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[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://pubmed.ncbi.nlm.nih.gov/2943992 PubMed]
+# '''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]
 ==Idarubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:54jbs9|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:3y2de2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 241: / Line 60: @@
 |-
 |}
+''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.''
-''Unlikely to be completed, here for historic context only.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Idarubicin (Idamycin)]]
+*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-*[[Asparaginase (Elspar)]]
+*[[Asparaginase (Elspar)]] 7500 IU/m<sup>2</sup> IV once per day on days 10, 13, 16, 19, 22, 25
-*[[Vincristine (Oncovin)]]
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]] IV
+*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO or IV once per day on days 1 to 21
+'''35-day course'''
+</div></div>
 ===References===
-#'''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] [https://pubmed.ncbi.nlm.nih.gov/15256423/ PubMed] NCT00483132
+#'''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]
-==L-Asparaginase, Vincristine, Dexamethasone {{#subobject:54ea09|Regimen=1}}==
-===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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full 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" |
-|-
-|}
-''Unlikely to be completed, here for historic context only.''
-====Chemotherapy====
-*[[Asparaginase (Elspar)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[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; 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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full 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://www.thelancet.com/journals/lancet/article/PIIS0140673606695585/fulltext 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}}==
-===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://www.nature.com/articles/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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full 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
-|-
-|}
-''Unlikely to be completed, here for historic context only.''
-====Chemotherapy====
-*[[Asparaginase (Elspar)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[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://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://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full 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://www.thelancet.com/journals/lancet/article/PIIS0140673606695585/fulltext 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:#ee6b6e">
 ===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%"|Dates 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://doi.org/10.1016/0145-2126(79)90036-5 Henderson et al. 1979 (CALGB 7113)]
@@ Line 360: / Line 89: @@
 | 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)
 |[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 |style="background-color:#d73027"|Inferior CR rate
-|-
-|[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://onlinelibrary.wiley.com/doi/abs/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" |
 |-
 |}
-''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====
-*[[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
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[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>
-====Subsequent treatment====
-*CCC-1952: Consolidation
 ===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]
+# '''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 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] [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. [https://doi.org/10.1182/blood.V64.1.267.267 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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. [http://www.bloodjournal.org/content/64/1/267.long 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; 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://onlinelibrary.wiley.com/doi/abs/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:#ee6b6e">
 ===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%"|Dates 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)]
+|[https://doi.org/10.1182/blood.V13.12.1126.1126 Frei et al. 1958 (ALGB 01)]
-|NR
+|Not reported
 |style="background-color:#1a9851"|Randomized (E-switch-ic)
 |[[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]; alternate dosing
-|style="background-color:#ffffbf"|Seems not superior
+|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)]
 |1957-1960
 |style="background-color:#1a9851"|Randomized (E-esc)
-|1. [[#Mercaptopurine_monotherapy_88|6-MP]]<br>2. [[#Methotrexate_monotherapy_88|MTX]]
+|1. [[#Mercaptopurine_monotherapy_888|6-MP]]<br>2. [[#Methotrexate_monotherapy_888|MTX]]
-|style="background-color:#ffffbf"|Seems not superior
+|style="background-color:#ffffbf"|Did not meet endpoint of DOR
-|-
-|[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)]]
+*[[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===
-# '''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 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://pubmed.ncbi.nlm.nih.gov/5321112 PubMed]
-==Mercaptopurine & Prednisone {{#subobject:f609f5|Regimen=1}}==
+==Prednisolone monotherapy {{#subobject:5d40b1|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
-===Regimen {{#subobject:c637f6|Variant=1}}===
+===Regimen variant #1 {{#subobject:b66a94|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM196609012750901 Fernbach et al. 1966]
+|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
-|1960-1962
+|Not reported
-|style="background-color:#1a9851"|Randomized (C)
+| style="background-color:#91cf61" |Non-randomized
-|[[#Cyclophosphamide_.26_Prednisone_99|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://pubmed.ncbi.nlm.nih.gov/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;"
+!style="width: 33%"|Study
-===Regimen {{#subobject:b66a94|Variant=1}}===
+!style="width: 33%"|Dates of enrollment
-{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
+|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
+|Not reported
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Glucocorticoid therapy====
-*[[Prednisolone (Millipred)]]
+*[[Prednisolone (Millipred)]] 500 mg PO once per day on days 1 to 10
+'''10-day course'''
+</div></div>
 ===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://pubmed.ncbi.nlm.nih.gov/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}}==
+<div class="toccolours" style="background-color:#ee6b6e">
-===Regimen {{#subobject:07e67b|Variant=1}}===
+===Regimen variant #1 {{#subobject:07e67b|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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.nejm.org/doi/full/10.1056/NEJM195807312590502 Granville et al. 1958]
+|[https://doi.org/10.1056/NEJM195807312590502 Granville et al. 1958]
+|1955-1956
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[Prednisone (Sterapred)]] 125 mg PO twice per day on days 1 to 14, then tapered
-===References===
+'''One course'''
-# 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://pubmed.ncbi.nlm.nih.gov/13566450 PubMed]
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-=Consolidation after upfront therapy=
+===Regimen variant #2 {{#subobject:4te67b|Variant=1}}===
-==Mercaptopurine & Methotrexate {{#subobject:7a01b3|Regimen=1}}==
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
-===Regimen {{#subobject:752310|Variant=1}}===
+!style="width: 33%"|Dates of enrollment
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!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://www.nejm.org/doi/full/10.1056/NEJM198602203140803 Evans et al. 1986]
+|[https://doi.org/10.1056/NEJM195807312590502 Granville et al. 1958]
-|1979-1982
+|1955-1956
-|style="background-color:#1a9851"|Randomized (E-switch-ooc)
+| style="background-color:#91cf61" |Non-randomized
-|WBRT, then [[#Mercaptopurine_.26_Methotrexate_2|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===
-# 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://pubmed.ncbi.nlm.nih.gov/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=
 ==POMP {{#subobject:31219|Regimen=1}}==
 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}}===
-{| class="wikitable" style="width: 40%; 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.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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
 ====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
+*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+'''One course'''
+</div></div>
 ===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://pubmed.ncbi.nlm.nih.gov/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}}==
-===Regimen {{#subobject:028121|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://jamanetwork.com/journals/jama/article-abstract/656675 Selawry & Holland 1965 (ALGB 6313)]
-|1963
-|style="background-color:#1a9851"|Randomized (E-switch-ic)
-|[[#Methotrexate_monotherapy|MTX]]; oral
-| style="background-color:#1a9850" |Superior RFS
-|-
-|[https://jamanetwork.com/journals/jama/article-abstract/343520 Burgert et al. 1969 (ALGB 6311)]
-|NR
-|style="background-color:#1a9851"|Randomized (E-switch-ic)
-|[[#Methotrexate_monotherapy|MTX]]; oral
-| 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://pubmed.ncbi.nlm.nih.gov/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://pubmed.ncbi.nlm.nih.gov/4303512 PubMed]
 =Relapsed or refractory=
-==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e05416|Regimen=1}}==
+==BCG vaccine monotherapy {{#subobject:e05416|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:637e03|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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://doi.org/10.1016/s0140-6736(69)92648-8 Mathé et al. 1969]
+|Not reported
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====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://doi.org/10.1016/s0140-6736(69)92648-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4182654 PubMed]
-==Cyclophosphamide monotherapy {{#subobject:cd166d|Regimen=1}}==
-===Regimen {{#subobject:047e6a|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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://pubmed.ncbi.nlm.nih.gov/13892445 PubMed]
-==Daunorubicin & Prednisone {{#subobject:aa10e0|Regimen=1}}==
-===Regimen {{#subobject:19d9c6|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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)]]
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
 ===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://pubmed.ncbi.nlm.nih.gov/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]
-==L-Asparaginase, Vincristine, Prednisone {{#subobject:87ybf2|Regimen=1}}==
-===Regimen {{#subobject:a61pz6|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://pubmed.ncbi.nlm.nih.gov/6945911 Anderson et al. 1981]
-|NR in abstract
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#L-Asparaginase.2C_Vindesine.2C_Prednisone_99|L-Asparaginase, Vindesine, Prednisone]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Chemotherapy====
-*[[Asparaginase (Elspar)]]
-*[[Vincristine (Oncovin)]]
-====Glucocorticoid therapy====
-*[[Prednisone (Sterapred)]]
-===References===
-# Anderson J, Krivit W, Chilcote R, Pyesmany A, Chard R, Hammond D. Comparison of the therapeutic response of patients with childhood acute lymphoblastic leukemia in relapse to vindesine versus vincristine in combination with prednisone and L-asparaginase: a phase III trial. Cancer Treat Rep. 1981 Nov-Dec;65(11-12):1015-9. [https://pubmed.ncbi.nlm.nih.gov/6945911 PubMed]
 ==Pentostatin monotherapy {{#subobject:aa19e0|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:19d2c6|Variant=1}}===
-{| class="wikitable" style="width: 40%; 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
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Pentostatin (Nipent)]]
+</div></div>
 ===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://pubmed.ncbi.nlm.nih.gov/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: '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:635694|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
@@ Line 700: / Line 299: @@
 !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
 |-
 |}
-''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====
 *[[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://www.nejm.org/doi/full/10.1056/NEJM195904022601401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13644566 PubMed]
+# 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%"|Years of enrollment
+!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-NR
+|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 per day on days 1, 8, 15, 22
+*[[Vincristine liposomal (Marqibo)]] 2.25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+'''7-day cycles'''
-'''28-day cycles'''
+</div></div>
 ===References===
-# '''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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979201/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169518 PubMed] NCT00495079
+# '''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:Historical regimens]]

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

Latest revision as of 12:17, 15 July 2024

Upfront induction therapy

Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone

Regimen

Chemotherapy

Glucocorticoid therapy

Supportive therapy

Subsequent treatment

References

Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

L-Asparaginase, Vincristine, Prednisone

Regimen

Chemotherapy

Glucocorticoid therapy

References

Mercaptopurine & Methotrexate

Regimen

Chemotherapy

References

Prednisolone monotherapy

Regimen variant #1

Glucocorticoid therapy

Regimen variant #2

Glucocorticoid therapy

References

Prednisone monotherapy

Regimen variant #1

Glucocorticoid therapy

Regimen variant #2

Glucocorticoid therapy

References

Late intensification

POMP

Regimen

Chemotherapy

Glucocorticoid therapy

References

Relapsed or refractory

BCG vaccine monotherapy

Regimen

Immunotherapy

References

Pentostatin monotherapy

Regimen

Chemotherapy

References

TBI, then auto HSCT

Regimen

Radiotherapy

References

Vincristine liposomal monotherapy

Regimen

Chemotherapy

References

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