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Home > HSCT Autologous conditioning - carmustine and thiotepa [Part THREE of MARIETTA for Diffuse large B-cell lymphoma with secondary CNS involvement]

HSCT Autologous conditioning - carmustine and thiotepa [Part THREE of MARIETTA for Diffuse large B-cell lymphoma with secondary CNS involvement]

Treatment Overview

This regimen is Part THREE of MARIETTA.


For Part ONE and TWO, see LYM NHL B-cell Diffuse large - with secondary CNS involvement - MATRix and R-ICE [Part ONE and TWO of MARIETTA].

For the Treatment Schema, see Additional details.


This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably. 

Cycle 1 - 60 days

Cycle length:
60

Hydration is recommended as per institutional practice and may need an individualised approach.


carmustine and thiotepa:

  • Dose adjustment for patients weight may be required.
  • See Dosing for bodyweight in Additional details.
  • Refer to latest literature or access https://anztct.org.au (registration required).

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from Day 5 until engraftment.

Cycle details

Cycle 1 - 60 days

Medication / Procedure Dose Route Days Max Duration
carmustine * 400 mg/m² intravenous -6 3 hours Min: 134 minutes
thiotepa 5 mg/kg Twice daily intravenous -5, -4 120 minutes
paracetamol * 1000 mg flat dosing oral administration 0
proMETHazine * 12.5 mg intravenous 0 1 minutes
Autologous stem cell transplant intravenous 0
filgrastim 5 microgram/kg Once daily subcutaneous injection 5

Hydration is recommended as per institutional practice and may need an individualised approach.


carmustine and thiotepa:

  • Dose adjustment for patients weight may be required.
  • See Dosing for bodyweight in Additional details.
  • Refer to latest literature or access https://anztct.org.au (registration required).

filgrastim: Give filgrastim 5 microgram/kg subcutaneously ONCE daily from Day 5 until engraftment.

Full details

Cycle 1 - 60 days

Day: -6

Medication Dose Route Max duration Details
carmustine * 400 mg/m² intravenous 3 hours Min: 134 minutes
Instructions:
  • Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.
  • Do not exceed an infusion rate of 3 mg/m2 per minute. 
  • Prepare solution in PVC-free bag and administer via polyethylene lined administration set.
  • Protect bag and administration line from light.
Additional details:

Day: -5

Medication Dose Route Max duration Details
thiotepa 5 mg/kg Twice daily intravenous 120 minutes
Instructions:
  • Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.
  • Every 12 hours.
  • Administer via a 0.2 micron in-line filter.
Additional details:

Day: -4

Medication Dose Route Max duration Details
thiotepa 5 mg/kg Twice daily intravenous 120 minutes
Instructions:
  • Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.
  • Every 12 hours.
  • Administer via a 0.2 micron in-line filter.
Additional details:

Day: 0

Medication / Procedure Dose Route Max duration Details
paracetamol * 1000 mg flat dosing oral administration
Instructions:

ONE hour prior to return of autologous stem cells, or as per institutional practice.
proMETHazine * 12.5 mg intravenous 1 minutes
Instructions:

ONE hour prior to return of autologous stem cells, or as per institutional practice.
Autologous stem cell transplant intravenous
Instructions:

Administer as per institutional practice.

Day: 5

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 5 until engraftment.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Additional details

Section 1: Treatment Schema

Section 2: Dosing for bodyweight

Supportive Care Factors

Factor Value
Antifungal prophylaxis: Routine antifungal prophylaxis recommended
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
Emetogenicity: Variable
Gastroprotection: Gastroprotection may be considered
Growth factor support: Recommended for primary prophylaxis
Hydration: Routine hydration recommended
Hypersensitivity / Infusion related reaction risk: High - routine premedication recommended
Irradiated blood components: Irradiation of blood components is recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Sinusoidal obstruction syndrome prophylaxis: Sinsuoidal obstruction prophylaxis may be considered
Tumour lysis syndrome prophylaxis: Tumour lysis syndrome prophylaxis may be considered

Emetogenicity: HIGH day -6; LOW days -5 and -4.


References

Doorduijn, J. K., G. W. van Imhoff, B. van der Holt, et al. 2017. "Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation: results of the HOVON 80 phase 2 study." Hematol Oncol 35(4): 497-503., PMID: 27530779

Ferreri, A. J. M., J. K. Doorduijn, A. Re, et al. 2021. "MATRix-RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): an international, single-arm, phase 2 trial." Lancet Haematol 8(2): e110-e121., PMID: 33513372

Ferreri, A. J., G. Donadoni, M. G. Cabras, et al. 2015. "High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial." J Clin Oncol 33(33):3903-3910., PMID: 26282634

Janson, B., P. Van Koeverden, S. W. Yip, et al. 2012. "Carmustine infusion reactions are more common with rapid administration." Support Care Cancer 20(10): 2531-2535., PMID: 22252549

Korfel, A., T. Elter, E. Thiel, et al. 2013. "Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas." Haematologica 98(3):364-370., PMID: 23242601

Bubalo J, Carpenter PA, et al; American Society for Blood and Marrow Transplantation practice guideline committee. Conditioning chemotherapy dose adjustment in obese patients: a review and position statement by the American Society for Blood and Marrow Transplantation practice guideline committee. Biol Blood Marrow Transplant. 2014 May;20(5):600-16. doi: 10.1016/j.bbmt.2014.01.019. Epub 2014 Jan 23., PMID: 24462742

Adienne SA FDA prescribing information Tepadina 1/2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208264s000lbl.pdf (accessed 26 May 2022).

Emcure NZ Limited BiCNU New Zealand Datasheet 29 April 2020 https://www.medsafe.govt.nz/profs/datasheet/b/bicnuinj.pdf Accessed 25 May 2022).

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

New Zealand Blood Service Transfusion Medicine Handbook Third Edition, 2016 https://www.nzblood.co.nz/assets/Transfusion-Medicine/PDFs/111G122.pdf (accessed 16 June 2022).

Doyle J, Raggatt M, Slavin M, McLachlan SA, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust. 2019 Jun;210(10):462-468. doi: 10.5694/mja2.50160. Epub 2019 May 19., PMID: 31104328

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.