Chronic myeloid leukemia - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main CML page for current regimens.

8 regimens on this page 8 variants on this page

Chronic phase, first-line therapy

Hydroxyurea & Interferon alfa-2a

Regimen

Study	Years 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
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

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

Chemotherapy

• Hydroxyurea (Hydrea)

Immunotherapy

• Interferon alfa-2a (Roferon-A)

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 PubMed NCT00025402

Interferon alfa monotherapy

Regimen

Study	Years 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

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

Immunotherapy

• Interferon alfa

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	Evidence
Schilling & Meyer 1956	Non-randomized, <20 pts
Unugur et al. 1957	Non-randomized

Of historic interest.

Chemotherapy

• Busulfan (Myleran)

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	Years of enrollment	Evidence
Porter et al. 1994	NR	Non-randomized, <20 pts

Patients had relapsed after allogeneic HSCT

Immunotherapy

• Interferon alfa-2b (Intron-A)
• DLI

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	Years of enrollment	Evidence
Koller & Miller 1986	NR	Pilot, <20 pts (RT)

Chemotherapy

• Hydroxyurea (Hydrea)
• Plicamycin (Mithracin)

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 PubMed

Vincristine & Prednisone

Regimen

Study	Evidence
Marks et al. 1978	Non-randomized

Chemotherapy

• Vincristine (Oncovin)

Glucocorticoid therapy

• Prednisone (Sterapred)

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 PubMed