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Home > HSCT Allogeneic conditioning Myeloablative Matched unrelated donor - Cy/TBI3/ATG [CYCLOPHOSPHamide followed by total body irradiation and Thymoglobuline] [3 day]

HSCT Allogeneic conditioning Myeloablative Matched unrelated donor - Cy/TBI3/ATG [CYCLOPHOSPHamide followed by total body irradiation and Thymoglobuline] [3 day]

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.


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
mesna * 60 mg/kg Once daily intravenous -5, -4 24 hours
sodium chloride 0.9 % intravenous -5, -4 120 minutes
CYCLOPHOSPHamide * 60 mg/kg Once daily intravenous -5, -4 120 minutes
sodium chloride 0.9 % intravenous -5, -4 120 minutes
Total body irradiation -3, -2, -1
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.


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: -5

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 Once daily 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.

Day: -4

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 Once daily 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.

Day: -3

Medication / Procedure Dose Route Max duration Details
Total body irradiation
Instructions:

Administer 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:

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 / Procedure Dose Route Max duration Details
Total body irradiation
Instructions:

Administer 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:

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 / Procedure Dose Route Max duration Details
Total body irradiation
Instructions:

Administer 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:

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
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:

  • HIGH days -5 and -4;
  • Radiotherapy-induced nausea and vomiting (RINV) -3, -2 and -1;
  • MINIMAL days +1, +3, +6 and +11.

References

Bredeson, C., J. LeRademacher, K. Kato, et al. 2013. "Prospective cohort study comparing intravenous busulfan to total body irradiation in hematopoietic cell transplantation." Blood 122(24):3871-3878.

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.

Copelan, E. A., B. R. Avalos, K. W. Ahn, et al. 2015. "Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation." Biol Blood Marrow Transplant 21(3):552-558.

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

Hartman, AR, Williams, SF, Dillon, JJ. 1998 "Survival, disease-free survival and adverse effects of conditioning for allogeneic bone marrow transplantation with busulfan/cyclophosphamide vs total body irradiation: a meta-analysis. "Bone Marrow Transplant ; 22:439.

Holter-Chakrabarty, J. L., N. Pierson, M. J. Zhang, et al. 2015. "The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia." Biol Blood Marrow Transplant 21(7):1251-1257.

Litzow, MR, Perez, WS, Klein, JP, et al. 2002 "Comparison of outcome following allogeneic bone marrow transplantation with cyclophosphamide-total body irradiation versus busulphan-cyclophosphamide conditioning regimens for acute myelogenous leukaemia in first remission". Br J Haematol ; 119 (4):1115.

Marks DI, Forman SJ, Blume KG et al. 2006."A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission".Biol Blood Marrow Transplant. Apr;12(4):438-53.

Marks, D. I., T. Wang, W. S. Perez, et al. 2010. "The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission." Blood 116(3):366-374, PMID: 20404137

Nagler, A., B. N. Savani, M. Labopin, et al. 2015. "Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis." Lancet Haematol 2(9):e384-392.

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.

Oliansky, D. M., B. Camitta, P. Gaynon, et al. 2012. "Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review." Biol Blood Marrow Transplant 18(4):505-522.

Oliansky, D. M., R. A. Larson, D. Weisdorf, et al. 2012. "The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review." Biol Blood Marrow Transplant 18(1):18-36 e16.

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

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).

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).

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.