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Home > HSCT Allogeneic conditioning Myeloablative Sibling - Bu/Cy [busulfan and CYCLOPHOSPHamide]

HSCT Allogeneic conditioning Myeloablative Sibling - Bu/Cy [busulfan and CYCLOPHOSPHamide]

Treatment Overview

Cycle 1 - 11 days

Cycle length:
11

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.

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 intravenous -3, -2 120 minutes
sodium chloride 0.9 % intravenous -3, -2 120 minutes
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.

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.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.

Day: -7

Medication Dose Route Max duration Details
CLONazepam * 0.5 mg Twice daily oral administration
Instructions:

Take TWICE a day.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
busulfan 3.2 mg/kg Once daily intravenous 3 hours
Instructions:

Initial dose: Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.

Additional details:

Day: -6

Medication Dose Route Max duration Details
CLONazepam * 0.5 mg Twice daily oral administration
Instructions:

Take TWICE a day.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
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.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
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.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
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.

  • This medicine may make you sleepy and make it dangerous to drive or operate machinery. Limit alcohol intake.
mesna * 60 mg/kg Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and continue for 24 hours after the last dose of CYCLOPHOSPHamide, or as per institutional practice.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to CYCLOPHOSPHamide infusion.
CYCLOPHOSPHamide * 60 mg/kg intravenous 120 minutes
Instructions:
  • Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.
  • Consider hydration in addition to that specified to achieve 3000 ml/m2/24 hours is recommended on days of high dose CYCLOPHOSPHamide and for 24 hours after, or as per institutional practice.


Additional details:
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After CYCLOPHOSPHamide infusion, or as per institutional practice.

Day: -2

Medication Dose Route Max duration Details
mesna * 60 mg/kg Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and continue for 24 hours after the last dose of CYCLOPHOSPHamide, or as per institutional practice.
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to CYCLOPHOSPHamide infusion.
CYCLOPHOSPHamide * 60 mg/kg intravenous 120 minutes
Instructions:
  • Dose adjustment for patients weight may be required, see Dosing for bodyweight, below.
  • Consider hydration in addition to that specified to achieve 3000 ml/m2/24 hours is recommended on days of high dose CYCLOPHOSPHamide and for 24 hours after, or as per institutional practice.


Additional details:
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After CYCLOPHOSPHamide infusion, or 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.

  • Adjust dose according to trough levels as per institutional practice.
  • Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.

Day: 0

Medication / Procedure Dose Route Max duration Details
ciclosPORIN 1.5 mg/kg Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • Adjust dose according to trough levels as per institutional practice.
  • Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.
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.

  • Adjust dose according to trough levels as per institutional practice.
  • Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.
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.

  • Adjust dose according to trough levels as per institutional practice.
  • Switch to oral therapy when tolerated, ensure correct conversion between IV and oral therapy.

Day: 3

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.
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.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 5

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 6

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.
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.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 8

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 9

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 10

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued, duration as per haematologist advice.

Day: 11

Medication Dose Route Max duration Details
ciclosPORIN [Dose - see details] Twice daily intravenous Min: 120 minutes
Instructions:

Every 12 hours.

  • 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 GVHD prophylaxis to be continued past day 11, duration as per haematologist advice.
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

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., PMID: 26429297

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., PMID: 6355849

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. , PMID: 15710597

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., PMID: 12595317

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., PMID: 12374452

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., PMID: 12374454

Lui H, Zhai Z, Song Z et al. 2013. “Busulfan plus fludarabine as a myeloablative conditioning 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 6:1., PMID: 23394705

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., PMID: 23129746

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., PMID: 26457908

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., PMID: 26550118

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., PMID: 23980086

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., PMID: 11739158

Tutschka PJ, Copelan EA, Klein JP.1987 "Bone Marrow Transplantation for acute leukemia following a new Busulfan and cyclophosphamide regimen". Blood 70:1382-1388., PMID: 3311203

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., PMID: 24065243

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

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).

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.