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Home > HSCT Allogeneic conditioning Myeloablative Matched unrelated donor - Flu/Bu4/ATG [fludarabine, busulfan, and Thymoglobuline]

HSCT Allogeneic conditioning Myeloablative Matched unrelated donor - Flu/Bu4/ATG [fludarabine, busulfan, and Thymoglobuline]

Treatment Overview

Cycle 1 - 11 days

Cycle length:
11

Hydration 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.

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
fludarabine * 40 mg/m² Once daily intravenous -5 to -2 60 minutes
CLONazepam * 0.5 mg Once daily oral administration -6
CLONazepam * 0.5 mg Twice daily oral administration -5 to -2
CLONazepam * 0.5 mg Once daily oral administration -1
busulfan 3.2 mg/kg Once daily intravenous -5 3 hours
busulfan [Dose - see details] Once daily intravenous -4, -3, -2 3 hours
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 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.

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: -6

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: -5

Medication Dose Route Max duration Details
fludarabine * 40 mg/m² Once daily intravenous 60 minutes Additional 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: -4

Medication Dose Route Max duration Details
fludarabine * 40 mg/m² Once daily intravenous 60 minutes Additional 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
fludarabine * 40 mg/m² Once daily intravenous 60 minutes Additional 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.
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:

Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.

  • Administer over a minimum of 6 hours via a 0.22 micron in-line filter.
Additional details:

Day: -2

Medication Dose Route Max duration Details
fludarabine * 40 mg/m² Once daily intravenous 60 minutes Additional 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.
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:

Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.

  • If the initial dose is well tolerated, subsequent doses may be administered over a minimum of 4 hours.
  • Administer via a 0.22 micron in-line filter.
Additional details:

Day: -1

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.
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:

Dosing and administration is specific to the Thymoglobuline® brand ONLY and is NOT interchangeable with other brands of antithymocyte immunoglobulin, rabbit.

  • If the initial dose is well tolerated, subsequent doses may be administered over a minimum of 4 hours.
  • Administer via a 0.22 micron in-line filter.
Additional 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
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 -5, -4, -3 and -2;
  • MINIMAL days +1, +3, +6 and +11.

References

Palmer, J., J. S. McCune, M. A. Perales, et al. 2016. "Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee." Biol Blood Marrow Transplant 22(11):1915-1925.

Andersson, B. S., M. de Lima, P. F. Thall, et al. 2008. "Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS." Biol Blood Marrow Transplant 14(6):672-684.

Andersson, B. S., P. F. Thall, B. C. Valdez, et al. 2017. "Fludarabine with pharmacokinetically guided IV busulfan is superior to fixed-dose delivery in pretransplant conditioning of AML/MDS patients." Bone Marrow Transplant 52(4):580-587.

Rubio, M. T., M. D'Aveni-Piney, M. Labopin, et al. 2017. "Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party." J Hematol Oncol 10(1):31.

Bhurani, D., M. Schifter and I. Kerridge. 2008. "Folinic acid administration following MTX as prophylaxis for GVHD in allogeneic HSCT centres in Australia and New Zealand." Bone Marrow Transplant 42(8):547-550.

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.

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.

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.

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):701-709.

Liu, H., X. Zhai, Z. Song, et al. 2013. "Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study." J Hematol Oncol 6:15.

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).

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).

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

Regimen details sometimes vary slightly from the published literature after recommendation by expert committee consensus.

* 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.