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Home > HSCT Allogeneic conditioning Reduced intensity Sibling - Flu/Mel [fludarabine and melphalan]

HSCT Allogeneic conditioning Reduced intensity Sibling - Flu/Mel [fludarabine and melphalan]

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.


melphalan:

  • Consider oral cryotherapy on Day -1 by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.

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 25 mg/m² Once daily intravenous -7 to -3 30 minutes
sodium chloride 0.9 % intravenous -2 120 minutes
melphalan 140 mg/m² intravenous -2 30 minutes
sodium chloride 0.9 % intravenous -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.


melphalan:

  • Consider oral cryotherapy on Day -1 by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.

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: -7

Medication Dose Route Max duration Details
fludarabine 25 mg/m² Once daily intravenous 30 minutes Additional details:

Day: -6

Medication Dose Route Max duration Details
fludarabine 25 mg/m² Once daily intravenous 30 minutes Additional details:

Day: -5

Medication Dose Route Max duration Details
fludarabine 25 mg/m² Once daily intravenous 30 minutes Additional details:

Day: -4

Medication Dose Route Max duration Details
fludarabine 25 mg/m² Once daily intravenous 30 minutes Additional details:

Day: -3

Medication Dose Route Max duration Details
fludarabine 25 mg/m² Once daily intravenous 30 minutes Additional details:

Day: -2

Medication Dose Route Max duration Details
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

Prior to melphalan infusion.
melphalan 140 mg/m² intravenous 30 minutes
Instructions:
  • Consider oral cryotherapy by giving patient ice to suck starting 15 minutes prior to, during and up to one hour after the melphalan infusion.
  • The total time from preparation to the completion of the infusion should not exceed 90 minutes.
Additional details:
sodium chloride 0.9 % intravenous 120 minutes
Quantity:1000 mL
Instructions:

After melphalan infusion.

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
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:

  • MINIMAL days -7 to -3 and days +1, +3, +6 and +11;
  • HIGH day -2.

References

Bryant, A., I. Nivison-Smith, E. S. Pillai, et al. 2014. "Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients." Bone Marrow Transplant 49(1):17-23., PMID: 24056743

Baron, F., M. Labopin, A. Peniket, et al. 2015. "Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation." Cancer 121(7):1048-1055., PMID: 25424330

Robin, M., R. Porcher, C. Wolschke, et al. 2016. "Outcome after Transplantation According to Reduced-Intensity Conditioning Regimen in Patients Undergoing Transplantation for Myelofibrosis." Biol Blood Marrow Transplant., PMID: 26970380

Rondelli, D., J. D. Goldberg, L. Isola, et al. 2014. "MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis." Blood 124(7):1183-1191., PMID: 24963042

Eom, K. S., S. H. Shin, J. H. Yoon, et al. 2013. "Comparable long-term outcomes after reduced-intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high-risk acute lymphoblastic leukemia in complete remission." Am J Hematol 88(8):634-641., PMID: 23620000

Rodriguez, R., A. Nademanee, N. Ruel, et al. 2006. "Comparison of reduced-intensity and conventional myeloablative regimens for allogeneic transplantation in non-Hodgkin's lymphoma." Biol Blood Marrow Transplant 12(12):1326-1334., PMID: 17162215

Thomson, K. J., E. C. Morris, A. Bloor, et al. 2009. "Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-Hodgkin's lymphoma." J Clin Oncol 27(3):426-432., PMID: 19064981

Pinana, J. L., R. Martino, J. Gayoso, et al. 2010. "Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials." Haematologica., PMID: 20107156

Alvarez, I., A. Sureda, M. D. Caballero, et al. 2006. "Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol." Biol Blood Marrow Transplant 12(2):172-183., PMID: 16443515

Anderlini P, Saliba R, Acholonu S et al. 2008."Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience Haematologica. Feb;93(2):257-64., PMID: 18223284

Chen, R., J. M. Palmer, L. Popplewell, et al. 2011. "Reduced intensity allogeneic hematopoietic cell transplantation can induce durable remission in heavily pretreated relapsed Hodgkin lymphoma." Ann Hematol 90(7):803-808., PMID: 21210120

Sahebi, F., Y. Shen, S. H. Thomas, et al. 2013. "Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study." Br J Haematol 160(2):199-206., PMID: 23151215

Shimoni, A., I. Hardan, F. Ayuk, et al. 2010. "Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myeloma: long-term follow-up." Cancer 116(15):3621-3630., PMID: 20564132

Kroger, N., A. Shimoni, G. Schilling, et al. 2010. "Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation." Br J Haematol 148(2):323-331., PMID: 19912215

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).

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

Nakagaki M, Button E, Keating A, Marsh J, Mitchell C, Birchley A, Kennedy GA. Hyperhydration is not necessary for high-dose melphalan in stem cell transplantation. Bone Marrow Transplant. 2020 Apr;55(4):827-829. doi: 10.1038/s41409-019-0586-1. Epub 2019 Jun 11., PMID: 31186515

* 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.