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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main CML page for current regimens.
Last updated on 2024-07-23:8 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	Shorter OS
Allan et al. 1995 	1986-1994 	Phase 3 (C)	Interferon alfa-n1	Shorter OS
====Chemotherapy====
*Busulfan (Myleran) 4 mg PO once per day
Continued indefinitely
===References===
#Galton DA. Myleran in chronic myeloid leukaemia; results of treatment. Lancet. 1953 Jan 31;264(6753):208-13. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==Hydroxyurea monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tura et al. 1994 (MI400) 	1986-1988 	Phase 3 (C)	Interferon alfa-2a 	Shorter OS
Allan et al. 1995 	1986-1994 	Phase 3 (C)	Interferon alfa-n1 	Shorter OS
Hehlmann et al. 2003 (CML-Study II)	1991-1994 	Phase 3 (C)	Hydroxyurea & Interferon alfa-2a	Shorter 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===
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
==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 	Longer OS
Hehlmann et al. 2007 (CML-Study III) 	1995-2001 	Phase 3 (E-de-esc)	Allo HSCT (no specific conditioning regimen)	Seems to have longer 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====
*Hydroxyurea (Hydrea) 40 mg/kg/day (route not specified; see dose modifications)
====Immunotherapy====
*Interferon alfa-2a (Roferon-A) 5,000,000 IU/m2/day (route not specified; see dose modifications)
Continued indefinitely
====Dose and schedule modifications====
*Hydroxyurea was adapted to normal WBC counts (5 to 15 x 109/L)
*Interferon alfa-2a was adapted to 2000 to 4000 WBC/ul and tolerability
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC 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. link to original article does not contain dosing details link to PMC article EuroPMC 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	Longer OS
Hehlmann et al. 1994	1983-1991 	Phase 3 (E-switch-ooc)	2. Hydrea 	Did not meet primary endpoint of OS
Note: This article does not specify the exact type of interferon alfa.
====Immunotherapy====
*Interferon alfa
Continued indefinitely
===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. link to original article EuroPMC
=Chronic phase, relapsed or refractory=
==Busulfan monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Schilling & Meyer 1956	Not reported 	Non-randomized, fewer than 20 pts
Unugur et al. 1957 	1953-10 to 1956-01 	Non-randomized
====Chemotherapy====
*Busulfan (Myleran)
===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. link to original article EuroPMC
# 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 EuroPMC
==Interferon alfa-2b & DLI==
DLI: Donor Lymphocyte Infusion
===Regimen===
Study 	Dates of enrollment	Evidence
Porter et al. 1994	Not reported 	Non-randomized, fewer than 20 pts
Note: Patients had relapsed after allogeneic HSCT
====Immunotherapy====
*Interferon alfa-2b (Intron-A)
*DLI
===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. link to original article EuroPMC
=Blast crisis=
==Hydroxyurea & Plicamycin==
===Regimen===
Study 	Dates of enrollment	Evidence
Koller & Miller 1986	Not reported 	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 on days 1 to 21
**WBC count more than 75 x 109/L up to 100 x 109/L: 3000 mg/day PO on days 1 to 21
**WBC count more than 50 x 109/L up to 75 x 109/L: 2000 mg/day PO on days 1 to 21
**WBC count more than 30 x 109/L up to 50 x 109/L: 1500 mg/day PO on days 1 to 21
**WBC count more than 15 x 109/L up to 30 x 109/L: 1000 mg/day PO on days 1 to 21
**WBC count more than 7.5 x 109/L up to 15 x 109/L: 500 mg/day PO on days 1 to 21
*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
21-day course
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Vincristine & Prednisone==
===Regimen===
Study 	Dates of enrollment	Evidence
Marks et al. 1978	Not reported 	Non-randomized
====Chemotherapy====
*Vincristine (Oncovin) 2 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 7
7-day cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Chronic myeloid leukemia regimens
Category:Disease-specific pages
Category:Myeloproliferative neoplasms
Category:Historical regimens