Systemic Anti-Cancer Therapy Regimen Library
HSCT Allogeneic conditioning Myeloablative Matched unrelated donor - Bu/Cy/ATG [busulfan, CYCLOPHOSPHamide and Thymoglobuline]
Treatment Overview
Cycle 1 - 11 days
Hydration in addition to that specified is recommended as per institutional practice and may need an individualised approach.
busulfan, initial dose:
- 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).
busulfan, subsequent doses:
- Dose to be determined by therapeutic drug monitoring.
CYCLOPHOSPHamide:
- 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).
- Monitor for syndrome of inappropriate secretion of ADH with high dose CYCLOPHOSPHamide.
Thymoglobuline:
- Dosing and administration in this regimen is specific to the Thymoglobuline® brand of antithymocyte immunoglobulin, rabbit.
- Note: Branded products of antithymocyte immunoglobulin, rabbit are NOT interchangeable including but not limited to, different dosing and administration requirements.
ciclosPORIN:
- Adjust dose according to trough levels as per institutional practice.
- Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.
- Oral ciclosPORIN for graft versus host disease (GVHD) prophylaxis to be continued, duration as per haematologist advice.
Cycle details
Cycle 1 - 11 days
Medication / Procedure | Dose | Route | Days | Max Duration |
---|---|---|---|---|
CLONazepam * | 0.5 mg Once daily | oral administration | -8 | |
CLONazepam * | 0.5 mg Twice daily | oral administration | -7 to -4 | |
CLONazepam * | 0.5 mg Once daily | oral administration | -3 | |
busulfan | 3.2 mg/kg Once daily | intravenous | -7 | 3 hours |
busulfan | [Dose - see details] Once daily | intravenous | -6, -5, -4 | 3 hours |
mesna * | 60 mg/kg Once daily | intravenous | -3, -2 | 24 hours |
sodium chloride | 0.9 % | intravenous | -3, -2 | 120 minutes |
CYCLOPHOSPHamide * | 60 mg/kg Once daily | intravenous | -3, -2 | 120 minutes |
sodium chloride | 0.9 % | intravenous | -3, -2 | 120 minutes |
paracetamol * | 1000 mg flat dosing | oral administration | -3, -2, -1 | |
proMETHazine * | 12.5 mg | intravenous | -3, -2, -1 | 1 minutes |
methylprednisolone * | 1 mg/kg | intravenous | -3, -2, -1 | 5 minutes |
Thymoglobuline * | 0.5 mg/kg | intravenous | -3 | Min: 6 hours |
Thymoglobuline * | 2 mg/kg Once daily | intravenous | -2, -1 | Min: 4 hours |
ciclosPORIN | 1.5 mg/kg Twice daily | intravenous | -1 to 2 | Min: 120 minutes |
ciclosPORIN | [Dose - see details] Twice daily | intravenous | 3 to 11 | Min: 120 minutes |
paracetamol * | 1000 mg flat dosing | oral administration | 0 | |
proMETHazine * | 12.5 mg | intravenous | 0 | 1 minutes |
Allogeneic stem cell transplant | intravenous | 0 | ||
metHOTREXATe | 15 mg/m² | intravenous | 1 | 5 minutes |
metHOTREXATe | 10 mg/m² | intravenous | 3, 6, 11 | 5 minutes |
Hydration in addition to that specified is recommended as per institutional practice and may need an individualised approach.
busulfan, initial dose:
- 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).
busulfan, subsequent doses:
- Dose to be determined by therapeutic drug monitoring.
CYCLOPHOSPHamide:
- 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).
- Monitor for syndrome of inappropriate secretion of ADH with high dose CYCLOPHOSPHamide.
Thymoglobuline:
- Dosing and administration in this regimen is specific to the Thymoglobuline® brand of antithymocyte immunoglobulin, rabbit.
- Note: Branded products of antithymocyte immunoglobulin, rabbit are NOT interchangeable including but not limited to, different dosing and administration requirements.
ciclosPORIN:
- Adjust dose according to trough levels as per institutional practice.
- Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.
- Oral ciclosPORIN for graft versus host disease (GVHD) prophylaxis to be continued, duration as per haematologist advice.
Full details
Cycle 1 - 11 days
Day: -8
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Once daily | oral administration |
Instructions:
Take at night.
|
Day: -7
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Twice daily | oral administration |
Instructions:
Take TWICE a day.
|
|
busulfan | 3.2 mg/kg Once daily | intravenous | 3 hours |
Instructions:
Additional details:
Initial dose: Dose adjustment for patients weight may be required, see Dosing for bodyweight, below. |
Day: -6
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Twice daily | oral administration |
Instructions:
Take TWICE a day.
|
|
busulfan | [Dose - see details] Once daily | intravenous | 3 hours |
Instructions:
Subsequent dose: Dose to be determined by therapeutic drug monitoring. |
Day: -5
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Twice daily | oral administration |
Instructions:
Take TWICE a day.
|
|
busulfan | [Dose - see details] Once daily | intravenous | 3 hours |
Instructions:
Subsequent dose: Dose to be determined by therapeutic drug monitoring. |
Day: -4
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Twice daily | oral administration |
Instructions:
Take TWICE a day.
|
|
busulfan | [Dose - see details] Once daily | intravenous | 3 hours |
Instructions:
Subsequent dose: Dose to be determined by therapeutic drug monitoring. |
Day: -3
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
CLONazepam * | 0.5 mg Once daily | oral administration |
Instructions:
Take in the morning.
|
|
mesna * | 60 mg/kg Once daily | intravenous | 24 hours |
Instructions:
Continuous infusion over 24 hours.
|
sodium chloride | 0.9 % | intravenous | 120 minutes |
Quantity:1000 mL
Instructions:
Prior to CYCLOPHOSPHamide infusion. |
CYCLOPHOSPHamide * | 60 mg/kg Once daily | intravenous | 120 minutes |
Instructions:
Additional details:
|
sodium chloride | 0.9 % | intravenous | 120 minutes |
Quantity:1000 mL
Instructions:
After CYCLOPHOSPHamide infusion, or as per institutional practice. |
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
|
proMETHazine * | 12.5 mg | intravenous | 1 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
methylprednisolone * | 1 mg/kg | intravenous | 5 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
Thymoglobuline * | 0.5 mg/kg | intravenous | Min: 6 hours |
Instructions:
Additional details:
Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.
|
Day: -2
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
mesna * | 60 mg/kg Once daily | intravenous | 24 hours |
Instructions:
Continuous infusion over 24 hours.
|
sodium chloride | 0.9 % | intravenous | 120 minutes |
Quantity:1000 mL
Instructions:
Prior to CYCLOPHOSPHamide infusion. |
CYCLOPHOSPHamide * | 60 mg/kg Once daily | intravenous | 120 minutes |
Instructions:
Additional details:
|
sodium chloride | 0.9 % | intravenous | 120 minutes |
Quantity:1000 mL
Instructions:
After CYCLOPHOSPHamide infusion, or as per institutional practice. |
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
|
proMETHazine * | 12.5 mg | intravenous | 1 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
methylprednisolone * | 1 mg/kg | intravenous | 5 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
Thymoglobuline * | 2 mg/kg Once daily | intravenous | Min: 4 hours |
Instructions:
Additional details:
Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.
|
Day: -1
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
|
proMETHazine * | 12.5 mg | intravenous | 1 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
methylprednisolone * | 1 mg/kg | intravenous | 5 minutes |
Instructions:
ONE hour prior to Thymoglobuline® infusion. |
Thymoglobuline * | 2 mg/kg Once daily | intravenous | Min: 4 hours |
Instructions:
Additional details:
Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.
|
ciclosPORIN | 1.5 mg/kg Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 0
Medication / Procedure | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | 1.5 mg/kg Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
ONE hour prior to return of allogeneic stem cells, or as per institutional practice. |
|
proMETHazine * | 12.5 mg | intravenous | 1 minutes |
Instructions:
ONE hour prior to return of allogeneic stem cells, or as per institutional practice. |
Allogeneic stem cell transplant | intravenous |
Instructions:
Administer as per institutional practice. |
Day: 1
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | 1.5 mg/kg Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
metHOTREXATe | 15 mg/m² | intravenous | 5 minutes |
Instructions:
Administer at least 24 hours after allogeneic stem cell infusion. |
Day: 2
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | 1.5 mg/kg Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 3
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
metHOTREXATe | 10 mg/m² | intravenous | 5 minutes |
Day: 4
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 5
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 6
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
metHOTREXATe | 10 mg/m² | intravenous | 5 minutes |
Day: 7
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 8
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 9
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 10
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
Day: 11
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
ciclosPORIN | [Dose - see details] Twice daily | intravenous | Min: 120 minutes |
Instructions:
Every 12 hours.
|
metHOTREXATe | 10 mg/m² | intravenous | 5 minutes |
Additional details
Section 1: Dosing for bodyweight
Supportive Care Factors
Factor | Value |
---|---|
Anticonvulsant prophylaxis: | Mandatory |
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 |
CMV monitoring: | Recommended |
Emetogenicity: | Variable |
Gastroprotection: | Gastroprotection may be considered |
Graft versus host disease prophylaxis: | Graft versus host disease prophylaxis is mandatory |
Hydration: | Routine hydration recommended |
Hypersensitivity / Infusion related reaction risk: | High - routine premedication recommended |
Irradiated blood components: | Irradiation of blood components is recommended |
Mesna uroprotection: | Routine mesna uroprotection 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 |
Antifungal prophylaxis: Inhibition of CYP3A4 by azole antifungals will lead to reduced ciclosPORIN clearance and increased toxicities. A reduced ciclosPORIN dose is required with close monitoring of ciclosPORIN levels—see prescribing information, or Interactions checker in the NZ Formulary (nzf.org.nz).
CMV monitoring:
- If allograft recipient +/- donor are CMV seropositive:
- CMV quantitative PCR monitoring of CMV viral load should commence day 14 and be repeated once a week.
- Evidence of CMV reactivation necessitates appropriate antiviral treatment.
Emetogenicity:
- MEDIUM days -7 to -4;
- HIGH days -3 and -2;
- MINIMAL days +1, +3, +6 and +11.
References
Andersson BS, Thall PF, Madden T et al. 2002 "Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia". Biol Blood Marrow Transplant ;8(9):477-85.
Ben-Barouch, S., O. Cohen, L. Vidal, et al. 2016. "Busulfan fludarabine vs busulfan cyclophosphamide as a preparative regimen before allogeneic hematopoietic cell transplantation: systematic review and meta-analysis." Bone Marrow Transplant 51(2):232-240.
Copelan, E. A., B. K. Hamilton, B. Avalos, et al. 2013. "Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI." Blood 122(24):3863-3870.
Kashyap A, Wingard J, Cagnoni P et al. 2002 "Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality". Biol Blood Marrow Transplant ;8(9):493-500.
Kim SE, Lee JH, Choi SJ et al. 2005 "Morbidity and non-relapse mortality after allogeneic bone marrow transplantation in adult leukemia patients conditioned with busulfan plus cyclophosphamide: a retrospective comparison of oral versus intravenous busulfan. Haematologica". Feb;90(2):285-6.
Lee, J. H., Y. D. Joo, H. Kim, et al. 2013. "Randomized trial of myeloablative conditioning regimens: busulfan plus cyclophosphamide versus busulfan plus fludarabine." J Clin Oncol 31(6):701-70.
Lei, X. R., H. L. Chen, F. X. Wang, et al. 2015. "Busulfan plus fludarabine compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematologic neoplasms: a meta-analysis." Int J Clin Exp Med 8(8):12064-12075.
Lui H, Zhai Z, Song Z et al. 2013. “Busulfan plus fludarabine as a myeloablative condiitoing regimen compared with buslfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicentre study”. J Hematol Oncol 6(15).
Nagler, A., V. Rocha, M. Labopin, et al. 2013. "Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen--a report from the acute leukemia working party of the European group for blood and marrow transplantation." J Clin Oncol 31(28):3549-3556.
Radich, J. P., T. Gooley, W. Bensinger, et al. 2003. "HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen." Blood 102(1):31-35.
Rambaldi, A., A. Grassi, A. Masciulli, et al. 2015. "Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative regimen for allogeneic haemopoietic stem-cell transplantation in patients with acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial." Lancet Oncol 16(15):1525-1536.
Santos GW, Tutschka PJ, Brookmeyer R et al.1983 "Marrow Transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide". N Engl J Med.Dec 1;309(22):1347-53.
Socie, G., R. A. Clift, D. Blaise, et al. 2001. "Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies." Blood 98(13):3569-3574.
Tutschka PJ, Copelan EA, Klein JP.1987 "Bone Marrow Transplantation for acute leukemia following a new Busulfan and cyclophosphamide regimen". Blood ;70:1382-1388.
Otsuka America Pharmaceutical, Inc. Busulfex Prescribing information January 2015 https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020954s014lbl.pdf (Accessed 27 May 2022).
BC Cancer Drug Manual busulfan monograph 1 May 2018 http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Busulfan%20monograph.pdf (Accessed 15 March 2023).
Sanofi-Aventis New Zealand Limited New Zealand Datasheet 12 December 2018 https://www.medsafe.govt.nz/profs/datasheet/t/thymoglobulineinf.pdf (Accessed 27 May 2022).
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).
* 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.