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

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[B-cell acute lymphoblastic leukemia|main B-ALL page]] for current regimens.
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[[#top|Back to Top]]
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[B-cell acute lymphoblastic leukemia|main B-ALL page]] for current regimens.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}  
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{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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=Upfront induction therapy=
 
=Upfront induction therapy=
−
==Cyclophosphamide, Doxorubicin, L-Asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
+
==Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone {{#subobject:6edd1f|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:0f2246|Variant=1}}===
 
===Regimen {{#subobject:0f2246|Variant=1}}===
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!Study
+
!style="width: 33%"|Study
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.nature.com/leu/journal/v16/n7/full/2402526a.html Takeuchi et al. 2002 (JALSG-ALL93)]
+
|[https://doi.org/10.1038/sj.leu.2402526 Takeuchi et al. 2002 (JALSG-ALL93)]
 +
|1993-1997
 
|style="background-color:#91cf61"|Non-randomized
 
|style="background-color:#91cf61"|Non-randomized
 
|-
 
|-
 
|}
 
|}
−
''Unlikely to be completed, here for historic context only.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]]
+
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 29
−
*[[Doxorubicin (Adriamycin)]]
+
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 3, 8 to 10
−
*[[Asparaginase (Elspar)|L-Asparaginase]]
+
*[[Asparaginase (Elspar)|L-Asparaginase]] 6000 IU/m<sup>2</sup> IV once per day on days 29 to 35
−
*[[Vincristine (Oncovin)]]
+
*[[Vincristine (Oncovin)]] 1.3 mg/m<sup>2</sup> (maximum dose of 2 mg) IV bolus once per day on days 1, 8, 15, 22
−
*[[Prednisolone (Millipred)]]
+
====Glucocorticoid therapy====
−
 
+
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 10
 +
====Supportive therapy====
 +
*[[: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'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Subsequent treatment====
 +
*Consolidation I (see paper for details)
 +
</div></div>
 
===References===
 
===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://www.nature.com/leu/journal/v16/n7/full/2402526a.html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12094249 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]
  
−
==Cytarabine, Daunorubicin, L-Asparaginase, Teniposide, Vincristine, Prednisone {{#subobject:177f43|Regimen=1}}==
+
==Idarubicin, L-Asparaginase, Vincristine, Prednisone {{#subobject:54jbs9|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<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%"|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://doi.org/10.1182/blood-2003-10-3560 Hunault et al. 2004 (GOELAL02)]
 +
|1994-1998
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Idarubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Idarubicin, L-asparaginase, Vincristine, Prednisone]]; oral prednisone
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of response rate
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
===Regimen {{#subobject:2c8cee|Variant=1}}===
+
''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.''
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
<div class="toccolours" style="background-color:#b3e2cd">
−
!Study
+
====Chemotherapy====
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
*[[Asparaginase (Elspar)]] 7500 IU/m<sup>2</sup> IV once per day on days 10, 13, 16, 19, 22, 25
 +
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
====Glucocorticoid therapy====
 +
*[[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] '''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, 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%"|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://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90733-6/abstract Rivera et al. 1991]
+
|[https://doi.org/10.1016/0145-2126(79)90036-5 Henderson et al. 1979 (CALGB 7113)]
 +
|1971-1976
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJM199802193380803 Evans et al. 1998]
+
|[https://doi.org/10.1182/blood.V64.1.267.267 Gottlieb et al. 1984 (CALGB 7612)]
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
|1976-1980
 +
|style="background-color:#1a9851"|Randomized (C)
 +
|[[B-cell_acute_lymphoblastic_leukemia#DOLP|DOLP]]
 +
|style="background-color:#d73027"|Inferior CR rate
 
|-
 
|-
 
|}
 
|}
 +
''Note: The asparaginase dosing shown here was that after a mid-protocol amendment due to excess toxicity.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Cytosar)]]
+
*[[Asparaginase (Elspar)]] 500 IU/kg IV once per day on days 16 to 25
−
*[[Daunorubicin (Cerubidine)]]
+
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 1, 8, 15
−
*[[Asparaginase (Elspar)]]
+
====Glucocorticoid therapy====
−
*[[Teniposide (Vumon)]]
+
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 21, then tapered off over days 22 to 28
−
*[[Vincristine (Oncovin)]]
+
'''28-day course'''
−
*[[Prednisone (Sterapred)]]
+
</div></div>
  
 
===References===
 
===References===
−
# Rivera GK, Raimondi SC, Hancock ML, Behm FG, Pui CH, Abromowitch M, Mirro J Jr, Ochs JS, Look AT, Williams DL, Hancock ML, Evans WE, Kun LE. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. Lancet. 1991 Jan 12;337(8733):61-6. [https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90733-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1670723 PubMed]
+
# '''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]
−
# Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med. 1998 Feb 19;338(8):499-505. [https://www.nejm.org/doi/full/10.1056/NEJM199802193380803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9468466 PubMed]
+
# '''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]
  
−
==L-Asparaginase, Vincristine, Dexamethasone {{#subobject:54ea09|Regimen=1}}==
+
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<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%"|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://doi.org/10.1182/blood.V13.12.1126.1126 Frei et al. 1958 (ALGB 01)]
 +
|Not reported
 +
|style="background-color:#1a9851"|Randomized (E-switch-ic)
 +
|[[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]; alternate dosing
 +
|style="background-color:#ffffbf"|Did not meet endpoints
 +
|-
 +
|[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_888|6-MP]]<br>2. [[#Methotrexate_monotherapy_888|MTX]]
 +
|style="background-color:#ffffbf"|Did not meet endpoint of DOR
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
''Note: this is one of the first combination regimens in hematology/oncology.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====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'''
 +
</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. [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. [https://doi.org/10.1182/blood.V18.4.431.431 link to original article] '''dosing details in manuscript have been reviewed by our editors'''
  
−
===Regimen {{#subobject:4c9de2|Variant=1}}===
+
==Prednisolone monotherapy {{#subobject:5d40b1|Regimen=1}}==
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
<div class="toccolours" style="background-color:#ee6b6e">
−
!Study
+
===Regimen variant #1 {{#subobject:b66a94|Variant=1}}===
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!Comparator
+
!style="width: 33%"|Study
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
 +
|Not reported
 +
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/101/10/3809.long Bostrom et al. 2003 (CCG-1922)]
+
|}
−
|style="background-color:#1a9851"|Phase III (E)
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisone|L-asparaginase, Vincristine, Prednisone]]
+
====Glucocorticoid therapy====
−
|style="background-color:#1a9850"|Superior EFS
+
*[[Prednisolone (Millipred)]] 50 mg PO once per day on days 1 to 10
 +
'''10-day course'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen variant #2 {{#subobject:b6ee94|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full Mitchell et al. 2005 (UK MRC ALL97)]
+
|[https://doi.org/10.1056/NEJM196206282662603 Shanbrom & Miller 1962]
−
|style="background-color:#1a9851"|Phase III (E)
+
|Not reported
−
|[[#L-Asparaginase.2C_Vincristine.2C_Prednisolone|L-asparaginase, Vincristine, Prednisolone]]
+
| style="background-color:#91cf61" |Non-randomized
−
|style="background-color:#1a9850"|Superior EFS
 
 
|-
 
|-
 
|}
 
|}
−
''Unlikely to be completed, here for historic context only.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Glucocorticoid therapy====
−
*[[Asparaginase (Elspar)]]
+
*[[Prednisolone (Millipred)]] 500 mg PO once per day on days 1 to 10
−
*[[Vincristine (Oncovin)]]
+
'''10-day course'''
−
*[[Dexamethasone (Decadron)]]
+
</div></div>
−
 
 
 
===References===
 
===References===
−
# '''CCG-1922:''' Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. [http://www.bloodjournal.org/content/101/10/3809.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12531809 PubMed]
+
# 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]
−
# '''UK MRC ALL97:''' Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15952999 PubMed]
 
  
−
==L-Asparaginase, Vincristine, Prednisolone {{#subobject:65692a|Regimen=1}}==
+
==Prednisone monotherapy {{#subobject:5eeb7e|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen variant #1 {{#subobject:07e67b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[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)]] 125 mg PO twice per day on days 1 to 14, then tapered
 +
'''One course'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen variant #2 {{#subobject:4te67b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM195807312590502 Granville et al. 1958]
 +
|1955-1956
 +
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 250 mg PO four times per day on days 1 to 14, then tapered
 +
'''One course'''
 +
</div></div>
 +
===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. [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]
  
−
===Regimen {{#subobject:4af0d5|Variant=1}}===
+
=Late intensification=
−
{| class="wikitable" style="width: 100%; text-align:center;"
+
==POMP {{#subobject:31219|Regimen=1}}==
−
!Study
+
POMP: '''<u>P</u>'''urinethol (Mercaptopurine), '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
<div class="toccolours" style="background-color:#ee6b6e">
−
!Comparator
+
===Regimen {{#subobject:93b1b3|Variant=1}}===
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full Mitchell et al. 2005 (UK MRC ALL97)]
+
|[https://doi.org/10.1001/jama.1976.03260360023019 Bodey et al. 1976]
−
|style="background-color:#1a9851"|Phase III (C)
+
|1970-03 to 1973-05
−
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
+
| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts
−
|style="background-color:#d73027"|Inferior EFS
 
 
|-
 
|-
 
|}
 
|}
−
''Unlikely to be completed, here for historic context only.''
+
''Note: POMP is still used in maintenance settings; this is marked historic because it is late intensification.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Asparaginase (Elspar)]]
+
*[[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
−
*[[Prednisolone (Millipred)]]
+
*[[Methotrexate (MTX)]] 7.5 mg/m<sup>2</sup> 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'''
 +
</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://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]
  
 +
=Relapsed or refractory=
 +
==BCG vaccine monotherapy {{#subobject:e05416|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:637e03|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[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====
 +
*[[BCG vaccine]]
 +
</div></div>
 
===References===
 
===References===
−
# '''UK MRC ALL97:''' Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO; Medical Research Council Childhood Leukaemia Working Party. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005 Jun;129(6):734-45. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05509.x/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15952999 PubMed]
+
# 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:d039d8|Regimen=1}}==
+
==Pentostatin monotherapy {{#subobject:aa19e0|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:19d2c6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(81)91491-4 Prentice et al. 1981]
 +
|Not reported
 +
| style="background-color:#ffffbe" |Pilot
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
===Regimen {{#subobject:a4174a|Variant=1}}===
+
====Chemotherapy====
−
{| class="wikitable" style="width: 100%; text-align:center;"  
+
*[[Pentostatin (Nipent)]]
−
!Study
+
</div></div>
−
![[Levels_of_Evidence#Evidence|Evidence]]
+
===References===
−
!Comparator
+
# 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]
−
![[Levels_of_Evidence#Efficacy|Efficacy]]
+
==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;"  
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/64/1/267.long Gottlieb et al. 1984]
+
|[https://doi.org/10.1056/NEJM195904022601401 McGovern et al. 1959]
−
|style="background-color:#1a9851"|Randomized (C)
+
| style="background-color:#ffffbe" |Pilot
−
|[[B-cell_acute_lymphoblastic_leukemia#Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Daunorubicin, L-Asparaginase, Vincristine, Prednisone]]
 
−
|style="background-color:#d73027"|Inferior CR rate
 
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pubmed/2665546 van der Does-van den Berg et al. 1989 (DCLSG ALL V)]
+
|}
−
|style="background-color:#1a9851"|Phase III (C)
+
''Note: This is of historic interest and likely the first reported use of autologous HSCT in the treatment of malignancy.''
−
|[[B-cell_acute_lymphoblastic_leukemia#Daunorubicin.2C_L-Asparaginase.2C_Vincristine.2C_Prednisone|Daunorubicin, L-Asparaginase, Vincristine, Prednisone]]
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|style="background-color:#ffffbf"|Seems not superior
+
====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://doi.org/10.1056/NEJM195904022601401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13644566/ PubMed]
 +
==Vincristine liposomal monotherapy {{#subobject:f19406|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:18f662|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|Dates of enrollment
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/101/10/3809.long Bostrom et al. 2003 (CCG-1922)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979201/ O'Brien et al. 2012 (RALLY)]
−
|style="background-color:#1a9851"|Phase III (C)
+
|2007 to not reported
−
|[[#L-Asparaginase.2C_Vincristine.2C_Dexamethasone|L-asparaginase, Vincristine, Dexamethasone]]
+
|style="background-color:#91cf61"|Phase 2 (RT)
−
|style="background-color:#d73027"|Inferior EFS
+
|ORR: 35%
 
|-
 
|-
 
|}
 
|}
−
''Unlikely to be completed, here for historic context only.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Asparaginase (Elspar)]]
+
*[[Vincristine liposomal (Marqibo)]] 2.25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
*[[Vincristine (Oncovin)]]
+
'''7-day cycles'''
−
*[[Prednisone (Sterapred)]]
+
</div></div>
−
 
 
 
===References===
 
===References===
−
# Gottlieb AJ, Weinberg V, Ellison RR, Henderson ES, Terebelo H, Rafla S, Cuttner J, Silver RT, Carey RW, Levy RN, Hutchinson JL, Raich P, Cooper MR, Wiernik P, Anderson JR, Holland JF. Efficacy of daunorubicin in the therapy of adult acute lymphocytic leukemia: a prospective randomized trial by Cancer and Leukemia Group B. Blood. 1984 Jul;64(1):267-74. [http://www.bloodjournal.org/content/64/1/267.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6375760 PubMed]
+
# '''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]
−
# '''DCLSG ALL V:''' van der Does-van den Berg A, van Wering ER, Suciu S, Solbu G, van 't Veer MB, Rammeloo JA, de Koning J, van Zanen GE. Effectiveness of rubidomycin in induction therapy with vincristine, prednisone, and L-asparaginase for standard risk childhood acute lymphocytic leukemia: results of a Dutch phase III study (ALL V); A report on behalf of the Dutch Childhood Leukemia Study Group (DCLSG). Am J Pediatr Hematol Oncol. 1989 Summer;11(2):125-33. [https://www.ncbi.nlm.nih.gov/pubmed/2665546 PubMed]
 
−
# '''CCG-1922:''' Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME; Children's Cancer Group. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 2003 May 15;101(10):3809-17. Epub 2003 Jan 16. [http://www.bloodjournal.org/content/101/10/3809.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12531809 PubMed]
 
−
 
 
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
[[Category:B-cell acute lymphoblastic leukemia regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Acute leukemias]]
+
[[Category:Acute lymphoblastic leukemias]]
−
[[Category:Pediatric cancers]]
+
[[Category:Pediatric hematologic neoplasms]]

Latest revision as of 12:17, 15 July 2024

Back to Top

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

11 regimens on this page
13 variants on this page


Upfront induction therapy

Cyclophosphamide, Doxorubicin, L-asparaginase, Vincristine, Prednisolone

Regimen

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

Chemotherapy

Glucocorticoid therapy

Supportive therapy

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

35-day course

Subsequent treatment

  • Consolidation I (see paper for details)

References

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

Idarubicin, L-Asparaginase, Vincristine, Prednisone

Regimen

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

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

Chemotherapy

Glucocorticoid therapy

35-day course

References

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

L-Asparaginase, Vincristine, Prednisone

Regimen

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

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

Chemotherapy

Glucocorticoid therapy

28-day course

References

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

Mercaptopurine & Methotrexate

Regimen

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

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

Chemotherapy

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

Continued indefinitely

References

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

Prednisolone monotherapy

Regimen variant #1

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

Glucocorticoid therapy

10-day course


Regimen variant #2

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

Glucocorticoid therapy

10-day course

References

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

Prednisone monotherapy

Regimen variant #1

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

Glucocorticoid therapy

One course


Regimen variant #2

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

Glucocorticoid therapy

One course

References

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

Late intensification

POMP

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

Regimen

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

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

Chemotherapy

Glucocorticoid therapy

One course

References

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

Relapsed or refractory

BCG vaccine monotherapy

Regimen

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

Immunotherapy

References

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

Pentostatin monotherapy

Regimen

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

Chemotherapy

References

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

TBI, then auto HSCT

TBI: Total Body Irradiation

Regimen

Study Evidence
McGovern et al. 1959 Pilot

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

Radiotherapy

References

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

Vincristine liposomal monotherapy

Regimen

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

Chemotherapy

7-day cycles

References

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