CNS leukemia

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12 regimens on this page
13 variants on this page


Note: these regimens are primarily culled from literature that describes them as part of a comprehensive treatment regimen. Original regimens can be found on the following pages:

CNS prophylaxis

Cytarabine & Methotrexate

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Regimen #1, 16 doses

Study Evidence
Thomas et al. 2006 Pilot, <20 pts

Chemotherapy

Given each cycle for a total of 16 intrathecal treatments

Regimen #2, 6 to 8 doses

Study Evidence
Thomas et al. 1999 Phase II
Thomas et al. 2003 Phase II
Ravandi et al. 2010 Phase II

Total number of doses depends on risk for CNS relapse based on serum lactate dehydrogenase (LDH) >1400 IU/L and/or proliferative index percentage of S + G2M >=14%.

Chemotherapy

Given each cycle (approximately every 3 weeks) for a total of 6 or 8 intrathecal treatments

References

  1. Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. link to original article contains verified protocol PubMed
  2. Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. Epub 2003 Oct 9. link to original article contains verified protocol PubMed
    1. Update: Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O' Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the frontline treatment of adult patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. Epub 2015 Feb 14. link to original article PubMed
  3. Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. link to original article contains verified protocol PubMed
    1. Update: Fayad L, Thomas D, Romaguera J. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma. 2007 Dec;8 Suppl 2:S57-62. PubMed
  4. Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010 Sep 23;116(12):2070-7. Epub 2010 May 13. link to original article contains verified protocol--parts of the protocol were not explicitly listed in this reference, which instead referred to Thomas et al. 2004 and Kantarjian et al. 2004 PubMed
    1. Update: Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. link to original article PubMed

Cytarabine, Methotrexate, Methylprednisolone -> Mercaptopurine & WBRT

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WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Intrathecal treatments are given on days 1 & 8 of induction, day 29 of each series of consolidation blocks, and day 1 of late intensification.

Chemotherapy

6 doses, followed before maintenance therapy initiation by:

Chemoradiotherapy

One course

References

  1. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to early article contains verified protocol PubMed

Cytarabine, Methotrexate, Prednisone

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Regimen

Study Evidence
Tsukasaki et al. 2007 (JCOG 9801) Non-randomized
Ishida et al. 2015 Non-randomized

Treatments were given after cycles 1, 3, and 5 after platelets > 70 × 109/L and within 2 days before the next cycle.

Chemotherapy

3 doses

References

  1. Tsukasaki K, Utsunomiya A, Fukuda H, Shibata T, Fukushima T, Takatsuka Y, Ikeda S, Masuda M, Nagoshi H, Ueda R, Tamura K, Sano M, Momita S, Yamaguchi K, Kawano F, Hanada S, Tobinai K, Shimoyama M, Hotta T, Tomonaga M; Japan Clinical Oncology Group Study JCOG9801. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study JCOG9801. J Clin Oncol. 2007 Dec 1;25(34):5458-64. Epub 2007 Oct 29. link to original article contains verified protocol PubMed
  2. Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R. Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. Br J Haematol. 2015 Jun;169(5):672-82. Epub 2015 Mar 2. link to original article PubMed

Methotrexate -> Cytarabine & WBRT

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WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Rowe et al. 2005 (MRC UKALL XII/ECOG E2993) Non-randomized portion of RCT

Chemotherapy, MTX portion

  • Methotrexate (MTX) as follows:
    • Phase 1: 12 mg IT once on day 15
    • Phase 2: 12 mg IT once per day on days 1, 8, 15, 22

Chemoradiotherapy

  • Cytarabine (Cytosar) as follows:
    • Consolidation & Maintenance: 50 mg IT once per week for 4 weeks, then once per quarter for 4 doses (8 doses, total)
  • Cranial irradiation to 2400 cGy, given during consolidation

References

  1. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16. link to original article contains verified protocol PubMed
    1. Update: Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29. link to original article PubMed
    2. Update: Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. Epub 2009 Feb 24. link to original article PubMed
    3. Update: Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. Epub 2013 Nov 25. link to original article contains verified protocol PubMed

Methotrexate & Hydrocortisone

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Regimen

Study Evidence
Kim et al. 2015 Phase II

Treatment can be started during or after induction.

Chemotherapy

Up to 10 doses

References

  1. Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, Kim DH, Kim K, Jung CW, Kim I, Yoon SS, Park S, Ahn JS, Yang DH, Lee JJ, Lee HS, Kim YS, Mun YC, Kim H, Park JH, Moon JH, Sohn SK, Lee SM, Lee WS, Kim KH, Won JH, Hyun MS, Park J, Lee JH, Shin HJ, Chung JS, Lee H, Eom HS, Lee GW, Cho YU, Jang S, Park CJ, Chi HS, Lee KH; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug 6;126(6):746-56. Epub 2015 Jun 11. link to original article contains verified protocol PubMed

Methotrexate & Methylprednisolone

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Regimen

Study Evidence
Lo-Coco et al. 2010 Non-randomized

It is not explicitly stated but presumably these are admixed and given together.

Chemotherapy

Total of 3 doses

References

  1. Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. link to original article contains verified protocol PubMed

Methotrexate & WBRT

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WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Linker et al. 1987 Phase II

Treatment is started within 1 week of achieving complete remission.

Chemoradiotherapy

  • Methotrexate (MTX) 12 mg IT once per week x 6 doses concurrent with radiation
  • Cranial irradiation, 18 Gy total given in 10 fractions over 12 to 14 days

References

  1. Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. link to original article contains verified protocol PubMed
    1. Update: Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. link to original article contains verified protocol PubMed

CNS treatment

Cytarabine & Methotrexate

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Regimen

Study Evidence
Thomas et al. 1999 Phase II

Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).

Chemotherapy

  • Methotrexate (MTX) as follows:
    • Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
    • First 4 weeks after cell count & cytology are negative: 12 mg (6 mg if given via Ommaya reservoir) IT once per week on weeks 1 & 3
    • Remainder of induction: 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2 of each cycle
  • Cytarabine (Cytosar) as follows:
    • Measurable CNS disease: 100 mg IT once per week
    • First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
    • Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle

References

  1. Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol. 1999 Aug;17(8):2461-70. link to original article contains verified protocol PubMed

Cytarabine, Methotrexate, Methylprednisolone -> Mercaptopurine & WBRT

back to top

WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Intrathecal treatments are given as follows: eight between days −7 and 21 of induction, four during the first two consolidation blocks, and one at day 29 of consolidation blocks 3 and 6.

Chemotherapy

14 doses, followed before HCT or maintanence initiation by:

Chemoradiotherapy

  • Mercaptopurine (Purinethol) 60 mg/m2/day during irradiation
  • Cranial irradiation as follows:
    • 15 Gy before HCT (details not provided), or
    • 24 Gy before maintenance therapy initiation (details not provided)

One course

References

  1. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to early article contains verified protocol PubMed

Cytarabine, Methotrexate, WBRT

back to top

WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Thomas et al. 2003 Phase II
Ravandi et al. 2010 Phase II

Note: while there is measurable CNS disease, both drugs are given every week, alternating, usually separated by at least 48 hours (e.g., on Mondays & Thursdays).

Chemoradiotherapy

  • Methotrexate (MTX) as follows:
    • Measurable CNS disease: 12 mg (6 mg if given via Ommaya reservoir) IT once per week
    • First 4 weeks after cell count & cytology are negative: 12 mg (6 mg if given via Ommaya reservoir) IT once per week on weeks 1 & 3
    • Remainder of induction: 12 mg (6 mg if given via Ommaya reservoir) IT once on day 2 of each cycle
  • Cytarabine (Cytosar) as follows:
    • Measurable CNS disease: 100 mg IT once per week
    • First 4 weeks after cell count & cytology are negative: 100 mg IT once per week on weeks 2 & 4
    • Remainder of induction: 100 mg IT once on day 7 or 8 of each cycle
  • Therapeutic external radiation is given to patients with CNS disease at presentation

References

  1. Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004 Jun 15;103(12):4396-407. Epub 2003 Oct 9. link to original article contains verified protocol PubMed
    1. Update: Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O' Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the frontline treatment of adult patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. Epub 2015 Feb 14. link to original article PubMed
  2. Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010 Sep 23;116(12):2070-7. Epub 2010 May 13. link to original article contains verified protocol--parts of the protocol were not explicitly listed in this reference, which instead referred to Thomas et al. 2004 and Kantarjian et al. 2004 PubMed
    1. Update: Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S, Burger JA, Rytting ME, Ferrajoli A, Wierda WG, Verstovsek S, Champlin R, Kebriaei P, McCue DA, Huang X, Jabbour E, Garcia-Manero G, Estrov Z, Kantarjian HM. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015 Dec 1;121(23):4158-64. Epub 2015 Aug 26. link to original article PubMed

Methotrexate (MTX)

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Regimen

Study Evidence
Huguet et al. 2009 (GRAALL-2003) Phase II

Chemotherapy

  • Methotrexate (MTX) as follows:
    • Prephase: 15 mg IT once at some point between days -7 and -4

References

  1. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lhéritier V, Macintyre E, Béné MC, Ifrah N, Dombret H. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009 Feb 20;27(6):911-8. Epub 2009 Jan 5. Erratum in: J Clin Oncol. 2009 May 20;27(15):2574. Dosage error in article text. link to early article contains verified protocol PubMed

Methotrexate & WBRT

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WBRT: Whole Brain Radiation Therapy

Regimen

Study Evidence
Linker et al. 1987 Phase II

Treatment starts while patient is receiving induction therapy.

Chemoradiotherapy

  • Methotrexate (MTX) as follows:
    • Induction: 12 mg IT once per week x 10 doses
    • Remainder of first year of therapy: 12 mg IT once per month
  • Cranial irradiation, 28 Gy total given (no details provided)

References

  1. Linker CA, Levitt LJ, O'Donnell M, Ries CA, Link MP, Forman SJ, Farbstein MJ. Improved results of treatment of adult acute lymphoblastic leukemia. Blood. 1987 Apr;69(4):1242-8. link to original article contains verified protocol PubMed
    1. Update: Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood. 1991 Dec 1;78(11):2814-22. link to original article contains verified protocol PubMed