Stem cell mobilization regimens

Section editor
	Talal Hilal, MD Mayo Clinic Phoenix, AZ THilalMD

Unlike the other chemotherapy regimen pages, this one is not disease-specific. Rather, this is meant to be a gathering point for all stem cell mobilization regimens.

11 regimens on this page 13 variants on this page

Stem cell mobilization, all lines of therapy

These are regimens intended to mobilize stem cells, very incomplete right now but will be filled in over time.

CAD & G-CSF

CAD: Cyclophosphamide, Adriamycin (Doxorubicin), Dexamethasone

Regimen

Study	Evidence
Lokhorst et al. 2009 (HOVON-50)	Non-randomized portion of RCT

This is reported as a stem cell mobilization regimen but presumably has anti-myeloma activity.

Preceding treatment

• TAD versus VAD induction

Chemotherapy

• Cyclophosphamide (Cytoxan) 1000 mg/m² IV once on day 1
• Doxorubicin (Adriamycin) 15 mg/m² IV once per day on days 1 to 4

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Growth factor therapy

• Filgrastim (Neupogen) 5 mcg/kg SC twice per day until collection completed

One course

Subsequent treatment

• High-dose melphalan, then auto HSCT or tandem high-dose melphalan, then auto HSCT (this was not a randomization but was pre-determined by the treating center)

References

1. HOVON-50: Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article contains dosing details in manuscript PubMed NCT00028886
   1. Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed

Cyclophosphamide & G-CSF

Regimen variant #1

Study	Evidence
Oakervee et al. 2005	Phase 2

Chemotherapy

• Cyclophosphamide (Cytoxan) 1500 mg/m² IV once on day 1

Growth factor therapy

• Lenograstim (Granocyte) 263 mcg SC once per day, starting on day 4

Stem cell collection begins on day 10 and continues until at least 2 × 10⁶ CD34+ cells/kg are collected.

Regimen variant #2

Study	Evidence
Royer et al. 2016	Phase 2

Chemotherapy

• Cyclophosphamide (Cytoxan) 3000 mg/m² IV once

Growth factor therapy

• Filgrastim (Neupogen) 10 mcg/kg SC once per day and continued until at least 4 × 10⁶ CD34+ cells/kg are collected

References

1. Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, Agrawal S, Stec J, Schenkein D, Esseltine DL, Cavenagh JD. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun;129(6):755-62. link to original article contains dosing details in manuscript PubMed
2. Royer B, Minvielle S, Diouf M, Roussel M, Karlin L, Hulin C, Arnulf B, Macro M, Cailleres S, Brion A, Brechignac S, Belhadj K, Chretien ML, Wetterwald M, Chaleteix C, Tiab M, Leleu X, Frenzel L, Garderet L, Choquet S, Fuzibet JG, Dauriac C, Forneker LM, Benboubker L, Facon T, Moreau P, Avet-Loiseau H, Marolleau JP; Intergroupe Francophone du Myélome. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2016 Jun 20;34(18):2125-32. Epub 2016 Apr 25. link to original article contains dosing details in abstract PubMed EudraCT 2009-016607-33

Cytarabine & G-CSF

Regimen variant #1, 2000 mg/m² x 8

Study	Evidence
Yanada et al. 2013 (JALSG APL205R)	Phase 2

Note: Target CD34+ cell dose: 2 × 10⁶/kg

Chemotherapy

• Cytarabine (Ara-C) 2000 mg/m² IV over 3 hours twice per day on days 1 to 4 (total dose: 16,000 mg/m²)

Growth factor therapy

• Filgrastim (Neupogen) starting on day 6 (dose, frequency not specified)

Regimen variant #2, 3000 mg/m² x 2

Study	Evidence
Abrey et al. 2003	Phase 2

Chemotherapy

• Cytarabine (Ara-C) 3000 mg/m² IV once per day on days 1 & 2

Growth factor therapy

• Filgrastim (Neupogen) 10 mcg/kg SC once per day, starting on day 4 and continued until stem cell collection complete

References

1. Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 2003 Nov 15;21(22):4151-6. link to original article contains dosing details in manuscript PubMed
2. JALSG APL205R: Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. link to original article contains dosing details in manuscript PubMed UMIN C000000302
3. MMMobil-COI-01: Czerw T, Sadus-Wojciechowska M, Michalak K, Najda J, Mendrek W, Sobczyk-Kruszelnicka M, Glowala-Kosinska M, Chwieduk A, Mitrus I, Smagur A, Holowiecki J, Giebel S. Increased Efficacy of Stem Cell Chemomobilization with Intermediate-Dose Cytarabine Plus Granulocyte Colony-Stimulating Factor (G-CSF) Compared with G-CSF Alone in Patients with Multiple Myeloma: Results of a Randomized Trial. Biol Blood Marrow Transplant. 2019 Feb;25(2):248-255. Epub 2018 Sep 26. link to original article PubMed NCT01908621

Cytarabine, Ifosfamide, G-CSF

Regimen

Study	Evidence
Colombat et al. 2006	Phase 2

Chemotherapy

• Cytarabine (Ara-C) 1000 mg/m² IV every 12 hours on days 1 & 2
• Ifosfamide (Ifex) 1500 mg/m² IV once per day on days 1 to 3

Growth factor therapy

• Filgrastim (Neupogen) (dose/frequency not specified)

References

1. Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A, Berthou C, Bay JO, Delepine R, Desablens B, Camilleri-Broët S, Linassier C, Lamy T. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 2006 Sep;38(6):417-20. link to original article contains dosing details in manuscript PubMed

CYVE & G-CSF

CYVE & G-CSF: CYtarabine, VEpesid (Etoposide), Granulocyte Colony Stimulating Factor

Regimen

Study	Evidence
Soussain et al. 2001	Pilot, >20 pts
Soussain et al. 2008	Phase 2

Note: Target collection dose not described; mobilization took place after the first course of CYVE salvage for CNS lymphoma.

Chemotherapy

• Cytarabine (Ara-C) by the following split schedule:
  • 2000 mg/m² IV over 3 hours once per day on days 2 to 5
  • 50 mg/m² IV over 12 hours once per day on days 1 to 5
• Etoposide (Vepesid) 200 mg/m² IV over 2 hours once per day on days 2 to 5

Growth factor therapy

• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 48 hours after end of chemotherapy

References

1. Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N, Belanger C, Achour E, Ribrag V, Gerber S, Delattre JY, Leblond V. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001 Feb 1;19(3):742-9. link to original article contains dosing details in manuscript PubMed
2. Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F, Casasnovas O, Dupriez B, Souleau B, Taksin AL, Gisselbrecht C, Jaccard A, Omuro A, Sanson M, Janvier M, Kolb B, Zini JM, Leblond V; Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008 May 20;26(15):2512-8. Epub 2008 Apr 14. link to original article contains dosing details in manuscript PubMed

DCEP & G-CSF

DCEP & G-CSF: Dexamethasone, Cyclophosphamide, Etoposide, Platinol (Cisplatin), Granulocyte Colony Stimulating Factor

Regimen

Study	Evidence
Corso et al. 2004	Phase 2

Note: Stem cells are mobilized and collected after each course of therapy.

Glucocorticoid therapy

• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Chemotherapy

• Cyclophosphamide (Cytoxan) 400 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m²)
• Etoposide (Vepesid) 40 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m²)
• Cisplatin (Platinol) 10 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m²)

Supportive therapy

• Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 48 hours after chemotherapy and continuing through stem cell collection

2 cycles (length not specified)

References

1. Corso A, Barbarano L, Zappasodi P, Cairoli R, Alessandrino EP, Mangiacavalli S, Ferrari D, Fava S, Fiumanò M, Frigerio G, Isa L, Luraschi A, Klersy C, De Paoli A, Vergani C, Banfi L, Perego D, Ucci G, Pinotti G, Savarè M, Uziel L, Vismara A, Morra E, Lazzarino M. The VAD-DCEP sequence is an effective pre-transplant therapy in untreated multiple myeloma. Haematologica. 2004 Sep;89(9):1124-7. link to original article contains dosing details in manuscript PubMed

EAR & G-CSF

EAR & G-CSF: Etoposide, Ara-C (Cytarabine), Rituximab, Granulocyte Colony Stimulating Factor

Regimen

Study	Years of enrollment	Evidence
Damon et al. 2009 (CALGB 59909)	2001-2004	Phase 2

Note: Text specified that PJP prophylaxis started during mobilization --although table 1 did not list it-- to continue until 3 months after auto HSCT.

Preceding treatment

• R-M-CHOP x 2 to 3 cycles

Chemotherapy

• Etoposide (Vepesid) 10 mg/kg/day IV continuous infusion over 96 hours, started on day 1 (total dose: 40 mg/kg)
• Cytarabine (Ara-C) 2000 mg/m² IV over 2 hours twice per day on days 1 to 4 (total dose: 16,000 mg/m²)

Targeted therapy

• Rituximab (Rituxan) 375 mg/m² IV once per day on days 6 & 13

Supportive therapy

• Filgrastim (Neupogen) 10 mcg/kg SC once per day, starting on day 14, to continue until peripheral blood stem cell collection is complete
• Levofloxacin (Levaquin) 500 mg PO once per day, starting on day 7, to continue until ANC greater than or equal to 500/uL
• Fluconazole (Diflucan) 200 mg PO once per day, starting on day 6, to continue until ANC greater than or equal to 500/uL
• Acyclovir (Zovirax) 200 mg PO three times per day, starting on day 6, to continue until 1 year after auto HSCT
• Trimethoprim-Sulfamethoxazole (Bactrim DS) prophylaxis

Daily leukapheresis to start when WBC count greater than or equal to 5 x 10⁹/L

Subsequent treatment

• Patients with adequate collection and meeting criteria: CBV with autologous HSCT

References

1. CALGB 59909: Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. link to original article contains dosing details in abstract link to PMC article PubMed

IGEV & G-CSF

IGEV & G-CSF: Ifosfamide, GEmcitabine, Vinorelbine, Granulocyte Colony Stimulating Factor

Regimen

Study	Evidence
Magagnoli et al. 2007	Phase 2

Chemotherapy

• Ifosfamide (Ifex) 2000 mg/m² IV over 2 hours once per day on days 1 to 4
• Gemcitabine (Gemzar) 800 mg/m² IV once per day on days 1 & 4
• Vinorelbine (Navelbine) 20 mg/m² IV once on day 1

Glucocorticoid therapy

• Prednisolone (Millipred) 100 mg PO once per day on days 1 to 4

Supportive therapy

• Mesna (Mesnex) 900 mg/m² IV three times per day on days 1 to 4, given at 0, 2, 4 hours after Ifosfamide (Ifex) (total dose: 10,800 mg/m²)
• Lenograstim (Granocyte) 263 mcg SC once per day on days 7 until at least 3 x 10⁶ CD34+ cells per kg of body weight were collected

Apheresis was performed when the peripheral blood CD34+ cell count exceeded 10 cells/ul.

References

1. Magagnoli M, Spina M, Balzarotti M, Timofeeva I, Isa L, Michieli M, Capizzuto R, Morenghi E, Castagna L, Tirelli U, Santoro A. IGEV regimen and a fixed dose of lenograstim: an effective mobilization regimen in pretreated Hodgkin's lymphoma patients. Bone Marrow Transplant. 2007 Dec;40(11):1019-25. Epub 2007 Oct 1. link to original article contains dosing details in manuscript PubMed

DexaBEAM & G-CSF

DexaBEAM & G-CSF: Dexamethasone, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan, Granulocyte Colony Stimulating Factor

Regimen

Study	Years of enrollment	Evidence
Dreyling et al. 2004	1996-2004	Non-randomized portion of RCT

Glucocorticoid therapy

• Dexamethasone (Decadron) 8 mg PO three times per day on days 1 to 10

Chemotherapy

• Carmustine (BCNU) 60 mg/m² IV once on day 2
• Etoposide (Vepesid) 75 mg/m² IV once per day on days 4 to 7
• Cytarabine (Ara-C) 100 mg/m² IV twice per day on days 4 to 7
• Melphalan (Alkeran) 20 mg/m² IV once on day 3

Growth factor therapy

• G-CSF starting on day 11

A minimum of 1 × 10⁶ CD34+ cells/kg are collected.

References

1. Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. link to original article contains dosing details in manuscript PubMed

Plerixafor & G-CSF

Regimen

Study	Evidence	Comparator	Comparative Efficacy
DiPersio et al. 2009 (Study 3101)	Phase 3 (E-switch-ic)	G-CSF	Superior primary endpoint

Growth factor therapy

• Plerixafor (Mozobil)
• G-CSF

References

1. Study 3101: DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E, Nademanee A, McCarty J, Bridger G, Calandra G; 3101 Investigators. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol. 2009 Oct 1;27(28):4767-73. Epub 2009 Aug 31. link to original article PubMed