Difference between revisions of "Chronic myeloid 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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 [[Chronic myeloid leukemia|main CML page]] for current regimens.
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<span id="BackToTop"></span>
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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
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[[#top|Back to Top]]
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</div>
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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 [[Chronic myeloid leukemia|main CML 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>
 
|}  
 
|}  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Chronic phase, first-line therapy=
 
=Chronic phase, first-line therapy=
 +
==Busulfan monotherapy {{#subobject:91n8u6|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:9buc75|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/10.1016/s0140-6736(53)90885-x Galton 1953]
 +
|1951
 +
| style="background-color:#ffffbe" |Case series
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1056/NEJM199403243301204 Tura et al. 1994 (MI400)]
 +
|1986-1988
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Chronic_myeloid_leukemia#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(95)92596-1 Allan et al. 1995]
 +
|1986-1994
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Chronic_myeloid_leukemia#Interferon_alfa-n1_monotherapy|Interferon alfa-n1]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Busulfan (Myleran)]] 4 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#Galton DA. Myleran in chronic myeloid leukaemia; results of treatment. Lancet. 1953 Jan 31;264(6753):208-13. [https://doi.org/10.1016/s0140-6736(53)90885-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/13097987/ PubMed]
 +
# '''MI400:''' Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, Zaccaria A, Fiacchini M; Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5. [https://doi.org/10.1056/NEJM199403243301204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8114834/ PubMed]
 +
# Allan NC, Richards SM, Shepherd PC; UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet. 1995 Jun 3;345(8962):1392-7. [https://doi.org/10.1016/s0140-6736(95)92596-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7760609/ PubMed]
 +
 +
==Hydroxyurea monotherapy {{#subobject:91i8gc|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#ee6b6e">
 +
===Regimen {{#subobject:1ygc75|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/10.1056/NEJM199403243301204 Tura et al. 1994 (MI400)]
 +
|1986-1988
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Chronic_myeloid_leukemia#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(95)92596-1 Allan et al. 1995]
 +
|1986-1994
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Chronic_myeloid_leukemia#Interferon_alfa-n1_monotherapy|Interferon alfa-n1]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1038/sj.leu.2403006 Hehlmann et al. 2003 (CML-Study II)]
 +
|1991-1994
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Hydroxyurea_.26_Interferon_alfa-2a|Hydroxyurea & Interferon alfa-2a]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Hydroxyurea (Hydrea)]] by the following weight-based criteria:
 +
**70 kg or less: 1500 mg/day PO
 +
**More than 70 kg: 2000 mg/day PO
 +
'''Continued indefinitely'''
 +
</div>
 +
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 +
*Physicians were "free to adjust the dose" to achieve leukocyte counts between 5 to 20 x 10<sup>9</sup>/L, "preferably in the lower part of this range"
 +
</div></div>
 +
===References===
 +
# '''MI400:''' Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, Zaccaria A, Fiacchini M; Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5. [https://doi.org/10.1056/NEJM199403243301204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8114834/ PubMed]
 +
# Allan NC, Richards SM, Shepherd PC; UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet. 1995 Jun 3;345(8962):1392-7. [https://doi.org/10.1016/s0140-6736(95)92596-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7760609/ PubMed]
 +
# '''CML-Study III:''' Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, Gratwohl A. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007 Jun 1;109(11):4686-92. Epub 2007 Feb 22. [http://www.bloodjournal.org/content/109/11/4686.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/17317858/ PubMed] [https://clinicaltrials.gov/study/NCT00002771 NCT00002771]
 +
 
==Hydroxyurea & Interferon alfa-2a {{#subobject:917a16|Regimen=1}}==
 
==Hydroxyurea & Interferon alfa-2a {{#subobject:917a16|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:909575|Variant=1}}===
 
===Regimen {{#subobject:909575|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 20: Line 108:
 
|1991-1994
 
|1991-1994
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Hydroxyurea_monotherapy_88|Hydroxyurea]]
+
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]
 
|style="background-color:#1a9850"|Superior OS
 
|style="background-color:#1a9850"|Superior OS
 
|-
 
|-
Line 27: Line 115:
 
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
|Allo HSCT (no specific conditioning regimen)
 
|Allo HSCT (no specific conditioning regimen)
−
| style="background-color:#91cf60" |Seems to have superior OS
+
| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4777774/ Gratwohl et al. 2015 (CML-Study IIIA)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4777774/ Gratwohl et al. 2015 (CML-Study IIIA)]
Line 43: Line 131:
 
*[[Interferon alfa-2a (Roferon-A)]]
 
*[[Interferon alfa-2a (Roferon-A)]]
 
</div></div>
 
</div></div>
 +
 
===References===
 
===References===
−
# '''CML-Study II:''' Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Queisser W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer JT, Perker M, Scheid C, Schenk M, Weiss J, Meier CR, Kremers S, Labedzki L, Schmeiser T, Lohrmann HP, Heimpel H; German CML Study Group. Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea. Leukemia. 2003 Aug;17(8):1529-37. [https://doi.org/10.1038/sj.leu.2403006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12886239 PubMed]
+
# '''CML-Study II:''' Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Queisser W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer JT, Perker M, Scheid C, Schenk M, Weiss J, Meier CR, Kremers S, Labedzki L, Schmeiser T, Lohrmann HP, Heimpel H; German CML Study Group. Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea. Leukemia. 2003 Aug;17(8):1529-37. [https://doi.org/10.1038/sj.leu.2403006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12886239/ PubMed]
−
# '''CML-Study III:''' Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, Gratwohl A. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007 Jun 1;109(11):4686-92. Epub 2007 Feb 22. [http://www.bloodjournal.org/content/109/11/4686.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/17317858 PubMed] NCT00002771
+
# '''CML-Study III:''' Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, Gratwohl A. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007 Jun 1;109(11):4686-92. Epub 2007 Feb 22. [http://www.bloodjournal.org/content/109/11/4686.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/17317858/ PubMed] [https://clinicaltrials.gov/study/NCT00002771 NCT00002771]
−
# '''CML-Study IIIA:''' Gratwohl A, Pfirrmann M, Zander A, Kröger N, Beelen D, Novotny J, Nerl C, Scheid C, Spiekermann K, Mayer J, Sayer HG, Falge C, Bunjes D, Döhner H, Ganser A, Schmidt-Wolf I, Schwerdtfeger R, Baurmann H, Kuse R, Schmitz N, Wehmeier A, Fischer JT, Ho AD, Wilhelm M, Goebeler ME, Lindemann HW, Bormann M, Hertenstein B, Schlimok G, Baerlocher GM, Aul C, Pfreundschuh M, Fabian M, Staib P, Edinger M, Schatz M, Fauser A, Arnold R, Kindler T, Wulf G, Rosselet A, Hellmann A, Schäfer E, Prümmer O, Schenk M, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, Büsche G, Haferlach C, Schnittger S, Müller MC, Reiter A, Berger U, Saußele S, Hochhaus A, Hehlmann R; SAKK; German CML Study Group. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment. Leukemia. 2016 Mar;30(3):562-9. Epub 2015 Oct 14. [https://www.nature.com/articles/leu2015281 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4777774/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26464170/ PubMed] NCT00025402
+
# '''CML-Study IIIA:''' Gratwohl A, Pfirrmann M, Zander A, Kröger N, Beelen D, Novotny J, Nerl C, Scheid C, Spiekermann K, Mayer J, Sayer HG, Falge C, Bunjes D, Döhner H, Ganser A, Schmidt-Wolf I, Schwerdtfeger R, Baurmann H, Kuse R, Schmitz N, Wehmeier A, Fischer JT, Ho AD, Wilhelm M, Goebeler ME, Lindemann HW, Bormann M, Hertenstein B, Schlimok G, Baerlocher GM, Aul C, Pfreundschuh M, Fabian M, Staib P, Edinger M, Schatz M, Fauser A, Arnold R, Kindler T, Wulf G, Rosselet A, Hellmann A, Schäfer E, Prümmer O, Schenk M, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, Büsche G, Haferlach C, Schnittger S, Müller MC, Reiter A, Berger U, Saußele S, Hochhaus A, Hehlmann R; SAKK; German CML Study Group. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment. Leukemia. 2016 Mar;30(3):562-9. Epub 2015 Oct 14. [https://www.nature.com/articles/leu2015281 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4777774/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26464170/ PubMed] [https://clinicaltrials.gov/study/NCT00025402 NCT00025402]
 
==Interferon alfa monotherapy {{#subobject:7d153e|Regimen=1}}==
 
==Interferon alfa monotherapy {{#subobject:7d153e|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:8dab8f|Variant=1}}===
 
===Regimen {{#subobject:8dab8f|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
Line 60: Line 149:
 
|rowspan=2|1983-1991
 
|rowspan=2|1983-1991
 
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
−
|1. [[#Busulfan_monotherapy_88|Busulfan]]
+
|1. [[#Busulfan_monotherapy|Busulfan]]
 
| style="background-color:#1a9850" |Superior OS
 
| style="background-color:#1a9850" |Superior OS
 
|-
 
|-
−
|2. [[#Hydroxyurea_monotherapy_88|Hydrea]]
+
|2. [[#Hydroxyurea_monotherapy|Hydrea]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
Line 70: Line 159:
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[:Category:Interferons|Interferon alfa]]
+
*[[:Category:Interferon alfas|Interferon alfa]]
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 +
 
===References===
 
===References===
−
# Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Löffler H, Hochhaus A, Heinze B, Georgii A, Bartram CR, Griesshammer M, Bergmann L, Essers U, Falge C, Queisser U, Meyer P, Schmitz N, Eimermacher H, Walther F, Fett W, Kleeberg UR, Kabisch A, Nerl C, Zimmermann R, Meuret G, Tichelli A, Kanz L, Tigges FJ, Schmid L, Brockhaus W, Tobler A, Reiter A, Perker M, Emmerich B, Verpoort K, Zankovich R, Wussow PV, Prummer O, Thiele J, Buhr T, Carbonell F, Ansari H; German CML Study Group. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood. 1994 Dec 15;84(12):4064-77. [http://www.bloodjournal.org/content/84/12/4064.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/7994025 PubMed]
+
# Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Löffler H, Hochhaus A, Heinze B, Georgii A, Bartram CR, Griesshammer M, Bergmann L, Essers U, Falge C, Queisser U, Meyer P, Schmitz N, Eimermacher H, Walther F, Fett W, Kleeberg UR, Kabisch A, Nerl C, Zimmermann R, Meuret G, Tichelli A, Kanz L, Tigges FJ, Schmid L, Brockhaus W, Tobler A, Reiter A, Perker M, Emmerich B, Verpoort K, Zankovich R, Wussow PV, Prummer O, Thiele J, Buhr T, Carbonell F, Ansari H; German CML Study Group. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood. 1994 Dec 15;84(12):4064-77. [http://www.bloodjournal.org/content/84/12/4064.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/7994025/ PubMed]
 +
 
 
=Chronic phase, relapsed or refractory=
 
=Chronic phase, relapsed or refractory=
 
==Busulfan monotherapy {{#subobject:24be30|Regimen=1}}==
 
==Busulfan monotherapy {{#subobject:24be30|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:b774ed|Variant=1}}===
 
===Regimen {{#subobject:b774ed|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/10.1056/NEJM195605242542104 Schilling & Meyer 1956]
 
|[https://doi.org/10.1056/NEJM195605242542104 Schilling & Meyer 1956]
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
|NR
 +
| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts
 
|-
 
|-
 
|[https://doi.org/10.1056/NEJM195704182561602 Unugur et al. 1957]
 
|[https://doi.org/10.1056/NEJM195704182561602 Unugur et al. 1957]
 +
|1953-10 to 1956-01
 
| style="background-color:#91cf61" |Non-randomized
 
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
Line 95: Line 189:
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Schilling RF, Meyer OO. Treatment of chronic granulocytic leukemia with 1, 4-dimethanesulfonyloxybutane (Myleran). N Engl J Med. 1956 May 24;254(21):986-9. [https://doi.org/10.1056/NEJM195605242542104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13322198 PubMed]
+
# Schilling RF, Meyer OO. Treatment of chronic granulocytic leukemia with 1, 4-dimethanesulfonyloxybutane (Myleran). N Engl J Med. 1956 May 24;254(21):986-9. [https://doi.org/10.1056/NEJM195605242542104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13322198/ PubMed]
−
# Unugur A, Schulman E, Dameshek W. Treatment of chronic granulocytic leukemia with Myleran. N Engl J Med. 1957 Apr 18;256(16):727-34. [https://doi.org/10.1056/NEJM195704182561602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13451927 PubMed]
+
# Unugur A, Schulman E, Dameshek W. Treatment of chronic granulocytic leukemia with Myleran. N Engl J Med. 1957 Apr 18;256(16):727-34. [https://doi.org/10.1056/NEJM195704182561602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13451927/ PubMed]
 +
 
 
==Interferon alfa-2b & DLI {{#subobject:5e6fed|Regimen=1}}==
 
==Interferon alfa-2b & DLI {{#subobject:5e6fed|Regimen=1}}==
 
DLI: '''<u>D</u>'''onor '''<u>L</u>'''ymphocyte '''<u>I</u>'''nfusion
 
DLI: '''<u>D</u>'''onor '''<u>L</u>'''ymphocyte '''<u>I</u>'''nfusion
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:26844e|Variant=1}}===
 
===Regimen {{#subobject:26844e|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
Line 108: Line 203:
 
|[https://doi.org/10.1056/NEJM199401133300204 Porter et al. 1994]
 
|[https://doi.org/10.1056/NEJM199401133300204 Porter et al. 1994]
 
|NR
 
|NR
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
| style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts
 
|-
 
|-
 
|}
 
|}
Line 118: Line 213:
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Porter DL, Roth MS, McGarigle C, Ferrara JL, Antin JH. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med. 1994 Jan 13;330(2):100-6. [https://doi.org/10.1056/NEJM199401133300204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8259165 PubMed]
+
# Porter DL, Roth MS, McGarigle C, Ferrara JL, Antin JH. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med. 1994 Jan 13;330(2):100-6. [https://doi.org/10.1056/NEJM199401133300204 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8259165/ PubMed]
 
=Blast crisis=
 
=Blast crisis=
 
==Hydroxyurea & Plicamycin {{#subobject:7d26h7|Regimen=1}}==
 
==Hydroxyurea & Plicamycin {{#subobject:7d26h7|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:af8acb|Variant=1}}===
 
===Regimen {{#subobject:af8acb|Variant=1}}===
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
Line 130: Line 225:
 
|[https://doi.org/10.1056/NEJM198612043152301 Koller & Miller 1986]
 
|[https://doi.org/10.1056/NEJM198612043152301 Koller & Miller 1986]
 
|NR
 
|NR
−
| style="background-color:#ffffbe" |Pilot, <20 pts (RT)
+
| style="background-color:#ffffbe" |Pilot, fewer than 20 pts (RT)
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Hydroxyurea (Hydrea)]]
+
*[[Hydroxyurea (Hydrea)]] by the following laboratory-based criteria:
−
*[[Plicamycin (Mithracin)]]
+
**WBC count more than 100 x 10<sup>9</sup>/L: 4000 mg/day PO
 +
**WBC count more than 75 x 10<sup>9</sup>/L up to 100 x 10<sup>9</sup>/L: 3000 mg/day PO
 +
**WBC count more than 50 x 10<sup>9</sup>/L up to 75 x 10<sup>9</sup>/L: 2000 mg/day PO
 +
**WBC count more than 30 x 10<sup>9</sup>/L up to 50 x 10<sup>9</sup>/L: 1500 mg/day PO
 +
**WBC count more than 15 x 10<sup>9</sup>/L up to 30 x 10<sup>9</sup>/L: 1000 mg/day PO
 +
**WBC count more than 7.5 x 10<sup>9</sup>/L up to 15 x 10<sup>9</sup>/L: 500 mg/day PO
 +
*[[Plicamycin (Mithracin)]] 25 mcg/kg IV over 2 to 4 hours once per day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27
 +
'''21-day course'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Koller CA, Miller DM. Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea. N Engl J Med. 1986 Dec 4;315(23):1433-8. [https://doi.org/10.1056/NEJM198612043152301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2431313/ PubMed]
+
# Koller CA, Miller DM. Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea. N Engl J Med. 1986 Dec 4;315(23):1433-8. [https://doi.org/10.1056/NEJM198612043152301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2431313/ PubMed]
 
==Vincristine & Prednisone {{#subobject:7d31e7|Regimen=1}}==
 
==Vincristine & Prednisone {{#subobject:7d31e7|Regimen=1}}==
−
<div class="toccolours" style="background-color:#eeeeee">
+
<div class="toccolours" style="background-color:#ee6b6e">
 
===Regimen {{#subobject:af8942|Variant=1}}===
 
===Regimen {{#subobject:af8942|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
Line 153: Line 255:
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Vincristine (Oncovin)]]
+
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV once on day 1
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]]
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 7
 +
'''7-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Marks SM, Baltimore D, McCaffrey R. Terminal transferase as a predictor of initial responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia: a co-operative study. N Engl J Med. 1978 Apr 13;298(15):812-4. [https://doi.org/10.1056/NEJM197804132981503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/273142/ PubMed]
+
# Marks SM, Baltimore D, McCaffrey R. Terminal transferase as a predictor of initial responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia: a co-operative study. N Engl J Med. 1978 Apr 13;298(15):812-4. [https://doi.org/10.1056/NEJM197804132981503 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/273142/ PubMed]
 
[[Category:Chronic myeloid leukemia regimens]]
 
[[Category:Chronic myeloid leukemia regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Myeloproliferative neoplasms]]
 
[[Category:Myeloproliferative neoplasms]]
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]

Revision as of 00:34, 14 June 2024

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

8 regimens on this page
8 variants on this page


Chronic phase, first-line therapy

Busulfan monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Galton 1953 1951 Case series
Tura et al. 1994 (MI400) 1986-1988 Phase 3 (C) Interferon alfa-2a Inferior OS
Allan et al. 1995 1986-1994 Phase 3 (C) Interferon alfa-n1 Inferior OS

Chemotherapy

Continued indefinitely

References

  1. Galton DA. Myleran in chronic myeloid leukaemia; results of treatment. Lancet. 1953 Jan 31;264(6753):208-13. link to original article contains dosing details in manuscript PubMed
  2. MI400: Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, Zaccaria A, Fiacchini M; Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5. link to original article PubMed
  3. Allan NC, Richards SM, Shepherd PC; UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet. 1995 Jun 3;345(8962):1392-7. link to original article contains dosing details in manuscript PubMed

Hydroxyurea monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tura et al. 1994 (MI400) 1986-1988 Phase 3 (C) Interferon alfa-2a Inferior OS
Allan et al. 1995 1986-1994 Phase 3 (C) Interferon alfa-n1 Inferior OS
Hehlmann et al. 2003 (CML-Study II) 1991-1994 Phase 3 (C) Hydroxyurea & Interferon alfa-2a Inferior OS

Chemotherapy

  • Hydroxyurea (Hydrea) by the following weight-based criteria:
    • 70 kg or less: 1500 mg/day PO
    • More than 70 kg: 2000 mg/day PO

Continued indefinitely

Dose and schedule modifications

  • Physicians were "free to adjust the dose" to achieve leukocyte counts between 5 to 20 x 109/L, "preferably in the lower part of this range"

References

  1. MI400: Tura S, Baccarani M, Zuffa E, Russo D, Fanin R, Zaccaria A, Fiacchini M; Italian Cooperative Study Group on Chronic Myeloid Leukemia. Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med. 1994 Mar 24;330(12):820-5. link to original article PubMed
  2. Allan NC, Richards SM, Shepherd PC; UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. UK Medical Research Council randomised, multicentre trial of interferon-alpha n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet. 1995 Jun 3;345(8962):1392-7. link to original article contains dosing details in manuscript PubMed
  3. CML-Study III: Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, Gratwohl A. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007 Jun 1;109(11):4686-92. Epub 2007 Feb 22. link to original article does not contain dosing details PubMed NCT00002771

Hydroxyurea & Interferon alfa-2a

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hehlmann et al. 2003 (CML-Study II) 1991-1994 Phase 3 (E-esc) Hydroxyurea Superior OS
Hehlmann et al. 2007 (CML-Study III) 1995-2001 Phase 3 (E-de-esc) Allo HSCT (no specific conditioning regimen) Seems to have superior OS (primary endpoint)
Gratwohl et al. 2015 (CML-Study IIIA) 1997-2004 Phase 3 (C) Allo HSCT (no specific conditioning regimen) Did not meet primary endpoint of OS

Note: One of the few regimens compared in large RCTs against allogeneic HSCT.

Chemotherapy

Immunotherapy

References

  1. CML-Study II: Hehlmann R, Berger U, Pfirrmann M, Hochhaus A, Metzgeroth G, Maywald O, Hasford J, Reiter A, Hossfeld DK, Kolb HJ, Löffler H, Pralle H, Queisser W, Griesshammer M, Nerl C, Kuse R, Tobler A, Eimermacher H, Tichelli A, Aul C, Wilhelm M, Fischer JT, Perker M, Scheid C, Schenk M, Weiss J, Meier CR, Kremers S, Labedzki L, Schmeiser T, Lohrmann HP, Heimpel H; German CML Study Group. Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea. Leukemia. 2003 Aug;17(8):1529-37. link to original article PubMed
  2. CML-Study III: Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A, Hossfeld DK, Huber C, Löffler H, Pralle H, Queisser W, Tobler A, Nerl C, Solenthaler M, Goebeler ME, Griesshammer M, Fischer T, Kremers S, Eimermacher H, Pfreundschuh M, Hirschmann WD, Lechner K, Wassmann B, Falge C, Kirchner HH, Gratwohl A. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007 Jun 1;109(11):4686-92. Epub 2007 Feb 22. link to original article does not contain dosing details PubMed NCT00002771
  3. CML-Study IIIA: Gratwohl A, Pfirrmann M, Zander A, Kröger N, Beelen D, Novotny J, Nerl C, Scheid C, Spiekermann K, Mayer J, Sayer HG, Falge C, Bunjes D, Döhner H, Ganser A, Schmidt-Wolf I, Schwerdtfeger R, Baurmann H, Kuse R, Schmitz N, Wehmeier A, Fischer JT, Ho AD, Wilhelm M, Goebeler ME, Lindemann HW, Bormann M, Hertenstein B, Schlimok G, Baerlocher GM, Aul C, Pfreundschuh M, Fabian M, Staib P, Edinger M, Schatz M, Fauser A, Arnold R, Kindler T, Wulf G, Rosselet A, Hellmann A, Schäfer E, Prümmer O, Schenk M, Hasford J, Heimpel H, Hossfeld DK, Kolb HJ, Büsche G, Haferlach C, Schnittger S, Müller MC, Reiter A, Berger U, Saußele S, Hochhaus A, Hehlmann R; SAKK; German CML Study Group. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment. Leukemia. 2016 Mar;30(3):562-9. Epub 2015 Oct 14. link to original article does not contain dosing details link to PMC article PubMed NCT00025402

Interferon alfa monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hehlmann et al. 1994 1983-1991 Phase 3 (E-switch-ooc) 1. Busulfan Superior OS
2. Hydrea Did not meet primary endpoint of OS

Note: This article does not specify the exact type of interferon alfa.

Immunotherapy

Continued indefinitely

References

  1. Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Queisser W, Löffler H, Hochhaus A, Heinze B, Georgii A, Bartram CR, Griesshammer M, Bergmann L, Essers U, Falge C, Queisser U, Meyer P, Schmitz N, Eimermacher H, Walther F, Fett W, Kleeberg UR, Kabisch A, Nerl C, Zimmermann R, Meuret G, Tichelli A, Kanz L, Tigges FJ, Schmid L, Brockhaus W, Tobler A, Reiter A, Perker M, Emmerich B, Verpoort K, Zankovich R, Wussow PV, Prummer O, Thiele J, Buhr T, Carbonell F, Ansari H; German CML Study Group. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood. 1994 Dec 15;84(12):4064-77. link to original article PubMed

Chronic phase, relapsed or refractory

Busulfan monotherapy

Regimen

Study Dates of enrollment Evidence
Schilling & Meyer 1956 NR Non-randomized, fewer than 20 pts
Unugur et al. 1957 1953-10 to 1956-01 Non-randomized

Chemotherapy

References

  1. Schilling RF, Meyer OO. Treatment of chronic granulocytic leukemia with 1, 4-dimethanesulfonyloxybutane (Myleran). N Engl J Med. 1956 May 24;254(21):986-9. link to original article PubMed
  2. Unugur A, Schulman E, Dameshek W. Treatment of chronic granulocytic leukemia with Myleran. N Engl J Med. 1957 Apr 18;256(16):727-34. link to original article PubMed

Interferon alfa-2b & DLI

DLI: Donor Lymphocyte Infusion

Regimen

Study Dates of enrollment Evidence
Porter et al. 1994 NR Non-randomized, fewer than 20 pts

Note: Patients had relapsed after allogeneic HSCT

Immunotherapy

References

  1. Porter DL, Roth MS, McGarigle C, Ferrara JL, Antin JH. Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med. 1994 Jan 13;330(2):100-6. link to original article PubMed

Blast crisis

Hydroxyurea & Plicamycin

Regimen

Study Dates of enrollment Evidence
Koller & Miller 1986 NR Pilot, fewer than 20 pts (RT)

Chemotherapy

  • Hydroxyurea (Hydrea) by the following laboratory-based criteria:
    • WBC count more than 100 x 109/L: 4000 mg/day PO
    • WBC count more than 75 x 109/L up to 100 x 109/L: 3000 mg/day PO
    • WBC count more than 50 x 109/L up to 75 x 109/L: 2000 mg/day PO
    • WBC count more than 30 x 109/L up to 50 x 109/L: 1500 mg/day PO
    • WBC count more than 15 x 109/L up to 30 x 109/L: 1000 mg/day PO
    • WBC count more than 7.5 x 109/L up to 15 x 109/L: 500 mg/day PO
  • Plicamycin (Mithracin) 25 mcg/kg IV over 2 to 4 hours once per day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27

21-day course

References

  1. Koller CA, Miller DM. Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea. N Engl J Med. 1986 Dec 4;315(23):1433-8. link to original article contains dosing details in manuscript PubMed

Vincristine & Prednisone

Regimen

Study Evidence
Marks et al. 1978 Non-randomized

Chemotherapy

Glucocorticoid therapy

7-day cycles

References

  1. Marks SM, Baltimore D, McCaffrey R. Terminal transferase as a predictor of initial responsiveness to vincristine and prednisone in blastic chronic myelogenous leukemia: a co-operative study. N Engl J Med. 1978 Apr 13;298(15):812-4. link to original article contains dosing details in manuscript PubMed
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