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Allogeneic reduced intensity conditioning fludarabine and melphalan

This protocol was published over 10 years ago and has been assessed by the reference committee as suitable to be reviewed as required. The review due date has been removed. If something in this protocol requires reference committee consideration, please click on the feedback button at the bottom of the page.

Read more about the as required review process in this factsheet.

There is evidence to support the use of post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis with this conditioning protocol.
Refer to ID 4428 GVHD prophylaxis Post-transplant cyclophosphamide (PTCy) for more details if intending to use PTCy instead of the GVHD prophylaxis listed below in the treatment schedule detail (e.g. ciclosporin and methotrexate).
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Drug Dose Route Day
Fludarabine 25 mg/m2 IV infusion -7 to -3
Melphalan 140 mg/m2 IV infusion -2
Infusion of stem cells 0

Alternative dosing regimens have been published using fludarabine 25 to 30 mg/m2 for 4 to 5 days in combination with melphalan 120 mg/m2, 140 mg/m2 or 180 mg/m2.rrr This may vary as per institutional standard practice, including dose reductions in patients over the age of 60 years of age.

Notes:
  • Alemtuzumab can be added to this protocol, doses of alemtuzumab vary in the literature and the optimal dose has not been established. Please refer to the evidence section for more information.
  • Antithymocyte globulins can be added to this protocol. Select link for information regarding antithymocyte globulins formulations and dosages.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Day -7 to -3
Fludarabine 25 mg/m2 (IV infusion) in 100 mL sodium chloride 0.9% over 30 minutes
Day -2
Melphalan 140 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 15 to 20 minutes

(or as per local institution). Infusion to be completed no later than 60 minutes after reconstitution
Day -1
ciclosPORIN 1.5 mg/kg (IV infusion) TWICE a day (12 hours apart) over 2 to 6 hours and continue until oral therapy can be tolerated
Day 0
Infusion of stem cells
Day 1
Methotrexate 15 mg/m2 (IV bolus) over 3 to 5 minutes (at least 24 hrs after stem cell/marrow infusion)
Day 3, 6, 11
Methotrexate 10 mg/m2 (IV bolus) over 3 to 5 minutes

Note: folinic acid rescue could be considered 24 hours post each methotrexate dose as it is associated with reduced toxicity and does not increase the risks of GVHD or graft rejection.r 

Drug Dose Route Day
Fludarabine 25 mg/m2 IV infusion -7 to -3
Melphalan 140 mg/m2 IV infusion -2
Infusion of stem cells 0

Alternative dosing regimens have been published using fludarabine 25 to 30 mg/m2 for 4 to 5 days in combination with melphalan 120 mg/m2, 140 mg/m2 or 180 mg/m2.rrr This may vary as per institutional standard practice, including dose reductions in patients over the age of 60 years of age.

Notes:
  • Alemtuzumab can be added to this protocol, doses of alemtuzumab vary in the literature and the optimal dose has not been established. Please refer to the evidence section for more information.
  • Antithymocyte globulins can be added to this protocol. Select link for information regarding antithymocyte globulins formulations and dosages.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Day -7 to -3
Fludarabine 25 mg/m2 (IV infusion) in 100 mL sodium chloride 0.9% over 30 minutes
Day -2
Melphalan 140 mg/m2 (IV infusion) in 250 mL sodium chloride 0.9% over 15 to 20 minutes

(or as per local institution). Infusion to be completed no later than 60 minutes after reconstitution
Day -1
ciclosPORIN 1.5 mg/kg (IV infusion) TWICE a day (12 hours apart) over 2 to 6 hours and continue until oral therapy can be tolerated
Day 0
Infusion of stem cells
Day 1
Methotrexate 15 mg/m2 (IV bolus) over 3 to 5 minutes (at least 24 hrs after stem cell/marrow infusion)
Day 3, 6, 11
Methotrexate 10 mg/m2 (IV bolus) over 3 to 5 minutes

Note: folinic acid rescue could be considered 24 hours post each methotrexate dose as it is associated with reduced toxicity and does not increase the risks of GVHD or graft rejection.r 

  • Haematological malignancies and non malignant haematological conditions
Venous access

Central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Antiemetics for multi-day protocols

Patients being treated with multi-day anticancer protocols should receive antiemetics tailored to the emetogenic risk of the drugs administered each day during treatment and for two days after completion of the anticancer protocol.

No standard antiemetic regimen exists for multi-day anticancer protocols. A combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies. 

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Proton pump inhibitor

Consider commencing a PPI on admission (or at the start of conditioning regimen) and continue throughout transplant.

Due to profound and long lasting inhibition of gastric acid, avoid concomitant administration with drugs such as mycophenolate mofetil, posaconazole syrup or itraconazole capsules (Of note, PPI is allowed with posaconazole tablet formulation).

In cases where PPI may be considered inappropriate, substitution with a H2 antagonist may be a suitable alternative at the discretion of the transplant physician.
Drug dosing in obese patients undergoing conditioning chemotherapy in BMT

There is limited evidence on dosing in this patient group due to a lack of randomised clinical trials and under reporting of data. Consider individual patient clinical factors (including organ dysfunction), pharmacokinetic and pharmacodynamic properties of anticancer drugs in the chosen regimen, recent published evidence and the availability of therapeutic drug monitoring when determining dose selection.

See ASBMT opens in a new tab or window for more information about dose adjustment of specific drugs in conditioning regimens in overweight and obese patients.
GVHD prophylaxis

Ciclosporin (CSA) and methotrexate

Commence CSA on day -1 (IV formulation) and change to PO formulation once tolerated. Adjust dose according to trough levels (target level = 150 to 300 ng/mL) 

Methotrexate to be given by IV bolus on day + 1, 3, 6 and 11

Note: if PO CSA therapy is changed to the IV formulation, the IV CSA dose is one-third to one-half of the previous total daily oral dose (Neoral® brand).
EBV monitoring

Reactivation of Epstein-Barr virus (EBV) infection and post-transplant lymphoproliferative disorder (PTLD) is a significant risk after allogeneic blood and marrow transplant (BMT). Regular EBV monitoring is highly recommended with this regimen. Consider regular monitoring for EBV reactivation by qPCR for 3 to 6 months post transplant and then as clinically indicated. Preemptive treatment is recommended.
CMV pre-transplant prophylaxis

In patients at high risk of CMV reactivation consider CMV prophylaxis. Practice may differ between institutions.
SOS prophylaxis

Stratify according to risk profile.

Read more about sinusoidal obstruction syndrome (SOS/VOD).
Tumour lysis risk

Assess patient for risk of developing tumour lysis syndrome.

Read more about the prevention and management of tumour lysis syndrome.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis

PJP prophylaxis is recommended.

Read about prophylaxis of pneumocystis jiroveci (carinii) in cancer patients
Antiviral prophylaxis (HSV)

Antiviral prophylaxis is recommended.

Read about antiviral prophylaxis drugs and doses
Antifungal prophylaxis

Antifungal prophylaxis is recommended.

Read more about antifungal prophylaxis drugs and doses.
Growth factor support

Consider the use of filgrastim from day +5 until recovery

Access the PBS website opens in a new tab or window
Blood product support

All transplant recipients are to receive irradiated blood products. Additionally, those patients who are CMV serologically negative are to receive CMV-negative or leukodepleted blood products (i.e. CMV safe), as dictated by local clinical policies.

Read more about the indications for the use of irradiated blood components opens in a new tab or window and cytomegalovirus (CMV) seronegative components opens in a new tab or window
Blood tests

FBC, EUC, eGFR, LFTs as required each day or as per clinician discretion. 
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility opens in a new tab or window
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
The International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) guideline does not address dose adjustment for kidney dysfunction in stem cell mobilisation, bone marrow transplantation and cellular therapies. In these circumstances, the transplant team should be consulted if the patient has kidney dysfunction and is requiring one of the drugs referred to in ADDIKD as part of their treatment. The dose recommendations in kidney dysfunction (i.e.renal impairment) displayed have been included for historical reference only.

Note: All dose reductions are calculated as a percentage of the starting dose

Renal impairment
Creatinine clearance (mL/min)
30 to 50 Reduce melphalan by 25% and fludarabine by 50%
less than 30

Reduce melphalan by 50%; fludarabine contraindicated
GVHD Prophylaxis
Ciclosporin Elimination is primarily biliary and renal failure does not alter ciclosporin clearance significantly. Monitor trough ciclosporin levels and adjust dose accordingly to avoid toxicity (target level = 150 to 300 ng/mL).
Methotrexate Dose reduction should be considered in significant renal impairment (50% dose reduction in methotrexate dose if eGFR between 25 to 50% of normal), significant pleural effusion, significant liver dysfunction such as hyperbilirubinaemia (>150 micromol/L) and/or severe mucositis.

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources:  

For more information see References & Disclaimer.

Fludarabine
  Interaction Clinical management
Dipyridamole Reduced efficacy of fludarabine possible due to inhibition of adenosine uptake Avoid combination or monitor for decreased clinical response to fludarabine
Melphalan (intravenous)
  Interaction Clinical management
Carmustine Increased risk of pulmonary toxicity. Intravenous melphalan may reduce the threshold for carmustine induced pulmonary toxicity Monitor closely for pulmonary toxicity
Ciclosporin Additive nephrotoxicity Monitor kidney function and ciclosporin levels: dose reduction of ciclosporin may be necessary when used with high dose melphalan
Methotrexate
  Interaction Clinical management
Ciprofloxacin

NSAIDS

Probenecid

Proton pump inhibitors (e.g. esomeprazole, omeprazole, pantoprazole)		 Increased toxicity of methotrexate possible due to reduced clearance Avoid combination or monitor for methotrexate toxicity

Important note: with high-dose methotrexate therapy, many of these drug combinations are contraindicated
Sulphonamides and penicillins (e.g. sulfamethoxazole (in Bactrim®, Septrin®), piperacillin (in Tazocin®) etc.) Increased toxicity of methotrexate possible due to displacement from serum protein binding Avoid combination or monitor for methotrexate toxicity
Trimethoprim Increased toxicity of methotrexate possible due to additive antifolate activity Avoid combination or monitor for methotrexate toxicity
Mercaptopurine Increased toxicity of mercaptopurine possible due to reduced clearance Avoid combination or monitor for mercaptopurine toxicity
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely
Hepatotoxic drugs (e.g. azathioprine, leflunomide, retinoids, sulfasalazine) Additive hepatotoxicity Avoid combination or monitor liver function closely
Folic acid (e.g. as in multivitamins)

Asparaginase (administered immediately prior or concurrently)		 Reduced efficacy of methotrexate possible due antagonism of its action Avoid combination or monitor for decreased clinical response to methotrexate
Note: asparaginase administered shortly after methotrexate can enhance its efficacy and reduce its toxicity
Infliximab Altered methotrexate concentration Monitor for signs of methotrexate toxicity or reduced efficacy
Azole antifungals
For a table of selected drug-drug interactions with azole antifungals link to the full text article by Chau et al 2014 opens in a new tab or window (refer to table 2)
Ciclosporin
  Interaction Clinical management
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely
Potassium sparing drugs (e.g. amiloride, eplerenone, spironolactone, ACE inhibitors, angiotensin II receptor antagonists etc.) Additive risk of hyperkalaemia Monitor potassium level closely if combination is used
Corticosteroids Corticosteroids are CYP3A4 substrates. Case reports of inhibition of CYP3A4 by corticosteroids, including high dose methylprednisolone and prednisolone, leading to increased levels of both agents If used in combination monitor ciclosporin level and assess for signs of steroid excess
Digoxin Digitalis toxicity due to decreased digoxin clearance Avoid combination or monitor for digitalis toxicity; dose reduction or withdrawal may be required
Etoposide Increased toxicity of etoposide possible due to reduced clearance Monitor for etoposide toxicity; adjust dose as needed
Colchicine, HMG-CoA reductase inhibitors (statins) Reduced clearance of colchicine and statins and etoposide, thereby enhancing the potential of these drugs to induce muscular toxicity, including muscle pain and weakness, myositis and occasionally rhabdomyolysis. If used concurrently, monitor closely for myotoxicity. Consider lower initial and maintenance dose of statin and cease immediately if signs and symptoms of myopathy occur
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of ciclosporin possible due to reduced clearance Avoid combination or monitor for ciclosporin toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John's wort etc.) Reduced efficacy of ciclosporin possible due to increased clearance Avoid combination or monitor for decreased clinical response to ciclosporin
Drugs metabolised by CYP3A4 (e.g. atorvastatin, benzodiazepines, calcineurin inhibitors, clarithromycin, dihydroergotamine, simvastatin, etc.) Increased effect/toxicity of these drugs possible due to inhibition of CYP3A4 by ciclosporin resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity Note: simvastatin and ivabradine contraindicated
Drugs undergoing P-gp-mediated elimination (e.g. dabigatran, loperamide, phenytoin etc.) Increased effects/toxicity of these drugs possible due to inhibition of P-gp by ciclosporin resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity
Infliximab Reduced ciclosporin concentrations possible due to increased clearance Monitor ciclosporin blood concentrations; adjust dosage as appropriate
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. If treating VTE, avoid use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window  inhibitors.

Dabigatran: avoid combination with strong P‑gp opens in a new tab or window inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update opens in a new tab or window

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day -7 to -3

Anti-cancer drug patient assessment tool prior to each day of treatment.

Prime IV line(s).

Access CVAD.

Note: a large volume of intravenous fluid may be given with this protocol. If weight increases by more than 1 kg from baseline or fluid balance becomes positive by one litre or any other signs of fluid overload are present, review by medical officer (diuretics may be required).

Hydration if prescribed.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Fludarabine

Administer fludarabine:
  • via IV infusion over 30 minutes
  • flush with ~ 50 mL of sodium chloride 0.9%.

Continue safe handling precautions until 7 days after completion of drug(s).

Day -2

Anti-cancer drug patient assessment tool prior to each day of treatment.

Note: a large volume of intravenous fluid may be given with this protocol. If weight increases by more than 1 kg from baseline or fluid balance becomes positive by one litre or any other signs of fluid overload are present, review by medical officer (diuretics may be required).

Hydration if prescribed.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Melphalan 

Prior to administration:

Consider administration of oral cryotherapy (ice) 15 minutes prior to and during melphalan infusion and up to one hour after infusion

Prehydration:
  • administer 1000 mL sodium chloride 0.9%  over ~ 2 hours
Administer melphalan (irritant with vesicant properties):
  • via IV infusion over 15 to 20 minutes
  • flush with ~100 mL of sodium chloride 0.9%
  • the infusion must be completed no later than 60 minutes after reconstitution
Post hydration:
  • administer 1000 mL sodium chloride 0.9% ~ over 2 hours

Continue safe handling precautions until 7 days after completion of drug(s).

Day -1

Anti-cancer drug patient assessment tool prior to each day of treatment.

Note: a large volume of intravenous fluid may be given with this protocol. If weight increases by more than 1 kg from baseline or fluid balance becomes positive by one litre or any other signs of fluid overload are present, review by medical officer (diuretics may be required).

Hydration if prescribed.

Verify antiemetics taken or administer as prescribed.

Ciclosporin 

  • administer via IV infusion over 2 to 6 hours (or as per institution; can be administered as divided doses or as a continuous 24 hour infusion)
  • use non PVC containers and tubing
  • flush with 100 mL sodium chloride 0.9%
  • facial flushing and headache may occur with too rapid infusion of ciclosporin: reduce infusion rate 
  • patients should be under continuous observation for at least the first 30 minutes following the start of the infusion and at frequent intervals thereafter
  • administer second dose of ciclosporin 12 hours after first dose.

Continue ciclosporin twice a day ongoing or as per haematologist advice

Continue safe handling precautions until 7 days after completion of drug(s).

Day 0

Anti-cancer drug patient assessment tool prior to each day of treatment.

Note: a large volume of intravenous fluid may be given with this protocol. If weight increases by more than 1 kg from baseline or fluid balance becomes positive by one litre or any other signs of fluid overload are present, review by medical officer (diuretics may be required).

Hydration if prescribed.

Treatment - Time out  

Continue GVHD prophylaxis as prescribed.

Commence antiviral and antifungal prophylaxis as prescribed.

Administer stem cells as per institutional guidelines.

Continue safe handling precautions until 7 days after completion of drug(s).

Day +1, 3, 6 and 11

Anti-cancer drug patient assessment tool prior to each day of treatment.

Note: a large volume of intravenous fluid may be given with this protocol. If weight increases by more than 1 kg from baseline or fluid balance becomes positive by one litre or any other signs of fluid overload are present, review by medical officer (diuretics may be required).

Hydration if prescribed.

Continue ciclosporin as prescribed.

Continue antiviral and antifungal prophylaxis as prescribed.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Methotrexate

Administer methotrexate:
  • via IV bolus via a side port of freely flowing IV fluids, over 3 to 5 minutes 
    OR
  • via a minibag, over 5 to 15 minutes
  • flush with ~50 mL of sodium chloride 0.9%.

Deaccess CVAD.

Continue safe handling precautions until 7 days after completion of drug(s).

Discharge information

Antiemetics - as/if prescribed.

Growth factor support - as/if prescribed, and arrangements for administration.

Ciclosporin capsules - with written instructions on how to take them.

Prophylaxis medications - as/if prescribed, i.e. antifungals, antivirals, PJP prophylaxis, tumour lysis prophylaxis.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Extravasation, tissue or vein injury

The unintentional instillation or leakage of a drug or substance out of a blood vessel into surrounding tissue. This has the potential to cause damage to affected tissue.

Read more about extravasation management
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Paraesthesia

'Pins and needles' and/or burning sensations in the hands and feet. It is associated with ciclosporin and usually occurs during the first week of treatment with a tendency to lessen over time. 
Taste and smell alteration

Read more about taste and smell changes

Early (onset days to weeks)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Hypertension

High blood pressure is commonly associated with many anti-cancer drugs. Pre-existing hypertension should be controlled prior to initiation of drugs capable of causing hypertension.
Nephrotoxicity

Kidney dysfunction resulting from damage to the glomeruli, tubules or renal vasculature.
Oesophagitis

Inflammation of the mucosal lining of the oesophagus.  It can progress to ulceration, haemorrhage, secondary infection and pain.
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following anti-cancer treatment, radiation therapy to the head, neck or oesophagus, and high-dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis and stomatitis
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Sinusoidal obstruction syndrome (SOS)

A serious and potentially fatal complication, presenting with hepatomegaly and/or right upper quadrant pain, jaundice and ascites. SOS typically occurs in the first 30 days following blood and marrow transplantation (BMT) although it can occur later.

Read more about sinusoidal obstruction syndrome (SOS/VOD)

Late (onset weeks to months)
Alopecia

Hair loss may occur from all parts of the body. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia and scalp cooling
Cognitive changes (chemo fog)

Changes in cognition characterised by memory loss, forgetfulness and feeling vague. This is also referred to as 'chemo brain' or 'chemo fog'.

Read more about cognitive changes (chemo fog) 
Drug induced gingival hyperplasia

Enlargement of the gingiva (gums).  In some cases, the gums may start to cover the teeth. Some patients may also experience bleeding and tenderness in the gums as a result of the enlargement.
Hirsutism

Excessive male-pattern hair growth in women is associated with ciclosporin; coarse dark hair can grow on the face, chest and back, under the arms and in the pubic area.
Neurotoxicity

Neurotoxicity related to fludarabine is a rare but potentially serious adverse event characterised by visual disturbances, altered mental state and CNS toxicity. Seizures leading to paralysis or coma have been reported in the literature. Periodic neurologic assessments are recommended.

Delayed (onset months to years)
Pulmonary toxicity

Pulmonary toxicity may include damage to the lungs, airways, pleura and pulmonary circulation. 

Read more about pulmonary toxicity associated with anti-cancer drugs

Fludarabine and melphalan (FluMel) reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) was initially described by the MD Anderson group, with a 2001 paper by Giralt et al.r The MD Anderson group demonstrated good engraftment and response rates balanced against tolerable toxicities in a cohort with a mixed range of haematological malignancies. The efficacy of FluMel HSCT has subsequently been demonstrated across a wide range of malignant and non-malignant haematological conditions. Key studies demonstrating the efficacy and toxicities of this regimen are tabulated below, after a brief overarching summary of evidence by disease group. 

Acute myeloid leukaemia and high-risk myelodysplasia 

Large registry studies support the long-term efficacy of FluMel RIC allograft in the acute myeloid leukaemia/myelodysplasia (AML/MDS) cohort. An EBMT registry study comparing FluMel to fludarabine and busulfan (FluBu) RIC allograft reported 2-year non-relapse mortality (NRM), overall survival (OS) and disease-free survival (DFS) of 20%, 62% and 60%, respectively, in the FluMel arm at a median follow-up of 3.5 years, with better disease control, higher treatment-related mortality (TRM) and comparable survival outcomes to FluBu conditioningr. An ABMTRR review with a median follow-up of 3.4 years reported a 1 year NRM, 3 year OS and DFS of 22%, 57% and 51% in patients with myeloid malignancies, 88% of whom had AML/MDS.r This study found NRM, OS and DFS outcomes in AML appeared better in those in complete remission 1 (CR1), human leukocyte antigen (HLA)-identical sibling transplants, cytomegalovirus (CMV) negative, and in the presence of chronic graft versus host disease (cGVHD). The optimal melphalan dose is unclear, with these registry studies including doses varying from 120-150 mg/m2 without comparison between dosing groups. Two studies comparing FluMel 140 and 180 demonstrated no clear survival benefit and higher non-lethal toxicity of the FluMel 180 regimen.rr One study comparing FluMel 100 and 140 found no difference in survival outcomes with the lower melphalan doser; another comparing FluMel 100 to FluMel 140/180 found similar survival outcomes if transplanted in CR, but due to low numbers, could not compare outcomes in active disease.r

Myelofibrosis

There is good evidence for the efficacy of FluMel RIC allograft in treatment of myelofibrosis (MF). A multicentre retrospective review comparing long-term transplant outcomes between FluBu and FluMel RIC allograft for MF found 7yr progression-free survival (PFS) and OS of 52% in the FluMel arm, with lower relapse rates (4% vs. 35.7%, p=0.008) and a trend to higher NRM (43% vs 31%, p=0.068) in the FluMel group, with no significant difference in OS outcomes between groups (52% vs 59%, p=0.08)r. A phase II prospective clinical trial investigated FluMel RIC allograft for MF comparing related to unrelated donor transplants and found superior engraftment and survival outcomes in patients undergoing transplants from related donors.r At a median of 25 months follow-up, they reported graft failure, NRM, OS and PFS rates of 6%, 22%, 75% and 71% in patients with related donors, compared with 36%, 59%, 32% and 32% in patients with unrelated donors. This suggests the potential to improve survival outcomes with patient/donor selection in this disease cohort.

Acute lymphoblastic leukaemia

FluMel RIC allograft appears to be a feasible conditioning regimen for acute lymphoblastic leukaemia (ALL), though evidence supporting its use limited. The largest study in this cohort is a retrospective review by Eom and colleagues, comparing 60 patients undergoing FluMel RIC allograft to 120 patients undergoing cyclophosphamide and total body irradiation (CyTBI) myeloablative conditioning (MAC) allograft. r Patients undergoing FluMel RIC allograft were significantly older (46 versus 33yrs, p < 0.001), patient characteristics were otherwise similar. At a median follow-up of 67 months, FluMel RIC and CyTBI MAC allograft had similar 5yr NRM (21% vs 24%, p=0.54) and OS (54% vs 58%, p=0.18); however a higher relapse rate was seen in the FluMel group (34% vs 26%), with a trend to lower DFS (51% vs 55%, p=0.07). Higher relapse risk was only seen in the subgroup of Philadelphia chromosome-positive patients undergoing FluMel RIC allograft.

Non-Hodgkin lymphoma

An early study by Rodriguez et al. found that, in a mixed cohort of patients with non-Hodgkin lymphoma (NHL) of different subtypes, FluMel RIC allograft appears to have comparable survival outcomes to TBI or busulfan and cyclophosphamide (BuCy) based MAC allograftr. Despite significantly higher relapse rates in the FluMel RIC group (28% vs 13%, p=0.05), survival did not differ significantly between groups, with 1yr TRM 28% vs 33% (p=0.40), 2yr OS 53% vs 52% (p=0.99), and 2yr PFS 40% vs 46% (p=0.46), respectively.
A subsequent ABMTRR registry study by Bryant et al. found FluMel RIC allograft appears to yield similar transplant outcomes for both lymphoid and myeloid malignancies when compared as disease groups.r A wide range of malignancies were compared (see table), with NHL accounting for 58% of patients within the lymphoid group and AML accounting for 71% of patients in the myeloid group. 3yr OS of 59% vs 57% (p=0.5) and 3yr DFS of 48% vs 51% (p=0.8) were reported in the lymphoid and myeloid groups, respectively, with lower rates of CR achieved in lymphoid malignancies (75% vs 90%, p=0.001).r
FluMel RIC allograft outcomes appear to vary by NHL subtype, with more aggressive disease subtypes having poorer outcomes. Sub-analysis of the ABMTRR study demonstrated a trend toward poorer 3yr OS in patients with diffuse large B-cell lymphoma (DLBCL) compared with chronic lymphocytic leukaemia (CLL)/follicular lymphoma (FL) (33% vs 64%, p=0.06). A multicentre retrospective review reported similar survival outcomes in a cohort of 48 patients with DLBCL undergoing FluMel RIC allograft with alemtuzumab, with 4yr NRM, OS and PFS of 32%, 47% and 48%, respectively.r Chemosensitive patients had significantly better 4yr OS than chemo-refractory patients (54% vs 12%, p=0.016).
Pinana and colleagues investigated FluMel RIC allograft for a cohort of 37 patients with FL, finding 4yr NRM, OS and DFS of 37%, 57% and 55%, respectively.r A trend toward improved OS was seen in patients in CR at transplant, compared with those with PR or PD (71%, 48% and 29%, p=0.09). Approximately one-third of this cohort received melphalan dosing of 80 mg/m2, though outcomes were not compared to the alternative 140 mg/m2 dose. A subsequent study by Ono et al. of 19 patients with FL undergoing RIC allograft with FluMel 140 mg/m2 conditioning reported 5yr TRM, OS and PFS of 15.8%, 84.2% and 84.2%, with no cases of disease progression at 75 months follow-up.r
Studies reporting outcomes of FluMel RIC allograft for mantle cell lymphoma (MCL) is less clear, with evidence limited to small retrospective reviews. A study by Cruz et al. of 21 patients with MCL undergoing FluMel RIC allograft found high engraftment rates, low 4yr NRM of 19.5%, and high 5yr OS and PFS of 80%. r 
Evidence for FluMel RIC allograft in T-cell lymphomas (TCL) is similarly limited. A small study of 27 patients with mature TCL’s by Delioukina and colleagues showed high neutrophil engraftment rates, with 2yr NRM, OS and PFS of 22%, 55% and 47%, respectively.r A trend to poorer outcomes was seen in cutaneous TCL compared with other histologies, with a 2-year OS of 45% vs 62% (p=0.38) and NRM of 27% versus 19% (p=NR).

Hodgkin lymphoma

Early retrospective reviews of transplant outcomes in Hodgkin lymphoma (HL) patients undergoing FluMel RIC yielded 2 yr OS in the range of 48-64% and PFS 27-32%.rrr A study of 67 patients with HL undergoing FluMel RIC allograft by Peggs et al. investigated the impact of GVH prophylaxis on outcomes.r The authors reported superior outcomes with alemtuzumab/ciclosporin compared with methotrexate/ciclosporin GVHD prophylaxis, with lower GVHD rates in the alemtuzumab group (29 vs. 42.9%, p=0.0034), and a corresponding trend to improved 4yr OS (39% vs 62%, p=0.0724) and 4yr PFS (25% vs 39%, p=0.0586). Chemosensitivity appears to predict transplant outcomes, with several studies reporting superior survival in HL patients with chemosensitive compared with chemo-refractory disease.rr A 2014 study by Chen et al. suggested that pre-treatment with potent agents such as brentuximab vedotin (BV) may result in better pre-transplant disease control/fitness and superior transplant outcomes.r The authors compared 21 contemporary BV-exposed patients to a historical cohort of 23 BV-naïve patients undergoing FluMel RIC allograft; there were no other significant demographic differences between groups. Higher pre-transplant CR rates (28.6% vs 4.3%, p=0.04) and lower haematopoietic stem cell transplantation - comorbidity index (HSCT-CI) (median 0 vs 2, p<0.01) were seen in the BV-exposed group, with superior transplant outcomes including lower rates of grade II-IV GVH (23.8% vs 47.8%, p=0.06) and higher PFS (59.3% vs 26.1%, p=0.03).

Multiple myeloma

Early studies investigating FluMel RIC allograft for multiple myeloma (MM) demonstrated high TRM/relapse and low survival, with two long-term follow-up studies finding 7yr OS and PFS of 25-34% and 20-26%, respectively.rrPatient/donor selection may improve transplant outcomes, with better survival seen in the subgroup of patients with good response to pre-transplant treatmentrr, early in disease courser and with HLA and gender-matched donors.rr Discouragingly, a study investigating long-term outcomes up to 10 years post FluMel RIC allograft for MM did not identify a plateau in late relapses, suggesting that the GVT effect may be inadequate for long-term disease control in this cohort.r Survival outcomes do not appear to be improved by variations in conditioning and GVHD prophylaxis regimens. A study by Bashir et al. of 50 MM patients undergoing FluMel RIC allograft investigated the impact of 100 mg/m2 versus 140 mg/m2 melphalan dosing on transplant outcome, finding no significant difference in OS (63% vs 45%, p=0.38) and PFS (41% vs 24%, p=0.12)r Kroger et al. compared outcomes of alemtuzumab versus ATG GVHD prophylaxis in 73 MM patients undergoing FluMel RIC, finding a trend to lower grade II-IV aGVHD rates in the alemtuzumab group (24% vs 47%, p=0.06), but higher relapse rates (HR 2.37, p=0.05), and no difference in 2yr OS (45% vs 54%, p=0.5) or 2yr PFS (36% vs 30%, p=0.5).r

Evidence Level (NHMRC) Study  Study Design Disease

Is the conditioning regimen consistent with the protocol? 

 Comments 
AML/MDS          
III-3 Baron et al.r Retrospective study AML Yes  Survey design study
III-3 Bryant et al.r Multicentre, retrospective study Myeloid and lymphoid malignancies Yes 

Dosing within the following ranges included: 

Fludarabine 25-30 mg/m2

Melphalan 120-160 mg/m2
MF          
III-3 Robin et al.r Multicentre, retrospective study MF No

Fludarabine 90 mg/m2 

Melphalan 140 mg/m2
III-2 Rondelli et al.r Phase II prospective study MF No

Fludarabine 30 mg/m2 (Day-6 to Day-2)

Melphalan 70 mg/m2 (Day-2 to Day-1)
ALL          
III-3 Eom et al.r Retrospective study ALL No

Fludarabine 150 mg/m2 

Melphalan 140 mg/m2
NHL           
III-3 Rodriguez et al.r Single centre, retrospective study NHL Yes -
III-3 Thomson et al.r Multicentre, retrospective study NHL (DLBCL) No Addition of alemtuzumab to conditioning regimen. 
III-1 Pinana et al.r Phase II prospective study NHL (FL) No

Dosing within the following ranges administered: 

Fludarabine 125-130 mg/m2

Melphalan 80-140 mg/m2
HL          
III-3 Alvarez et al.r Multicentre, retrospective study HL No 

Fludarabine 30 mg/m2 for 5 days

Melphalan 140 mg/m2 for 2 days
III-3 Anderlini et al.r Single centre, retrospective study HL No Fludarabine 25 mg/m2 daily for 5 days (Day -6 to Day-2) or 33 mg/m2 daily for 4 days (Day -5 to Day -2) 
Melphalan 70 mg/m2 daily for 2 days (Day -3 and Day-2)
III-2 Chen et al.r Single centre, retrospective study HL No Melphalan 140 mg/m2 given over 1 day only 
MM          
III-3 Sahebi et al.r Single centre, retrospective study MM No Melphalan 140 mg/m2 given over 1 day only 
III-3 Shimoni et al.r Multicentre, retrospective study MM No

Dosing within the following ranges administered: 

Fludarabine 90 - 150 mg/m2

Melphalan 100 -150 mg/m2
III-3 Kroger et al.r Phase II prospective study MM No

Fludarabine 30 mg/m2 (Day -6 to Day -4)

Melphalan 140 mg/m2 (Day -3)

Efficacy

Study No.of patients Donor/stem cell source NRM/TRM Relapse Rate OS DFS/PFS Comments 
AML/MDS              
Baron et al.r

394

  

2 yrs NRM 

FluMel 20% 

FluBu 18%

p=0.40

  

2 yr OS

FluMel 62%

FluBu 54% 

p=0.20 

2 yr DFS 

FluMel 60% 

FluBu 51% 

p=0.08

  
Bryant et al.r

344 

Myeloid malignancy n=234

(AML:166, MDS:40, MF:8, CML:15, Other:2)

Lymphoid malignancy n=110

(CLL:31, HL:12, FL:30, DLBCL:11, TCL:8, Other:18)

  

TRM 14% at day 100

TRM 22% at 1 yr

(NS difference in TRM between lymphoid/myeloid)

15% at 1 yr 

28% at 2 yrs 

20% at 3 yrs 

(NS difference in relapse rate between myeloid and lymphoid malignancies) 

3 yr OS 

Myeloid 57% 

Lymphoid 59% 

p=0.5

(NS difference in OS between myeloid and lymphoid malignancies)

3 yr DFS 

Myeloid 51% 

Lymphoid 48%

p=0.8 

(NS difference in DFS between myeloid and lymphoid malignancies)

  
MF              
Robin et al.r 160  

7 yr NRM

FluMel 43% 

FluBu 31% 

p=0.068 

  

7 yr OS 

FluMel 52% 

FluBu 59% 

p=0.08 

 

  
Rondelli et al.r 66  

NRM at 25 months 

Patients with related donors: 22%

Patients with unrelated donors: 59%

  

OS at 25 months

Patients with related donors: 75% 

Patients with unrelated donors: 32% 

PFS at 25 months 

Patients with related donors: 71% 

Patients with unrelated donors: 32% 

  
ALL              
Eom et al.r 180   

5 yr NRM 

FluMel 21.2% 

CyTBI 24.3% 

p=0.54

5 yr relapse risk 

FluMel 34.2% 

CyTBI 26.4%

p=0.019

5 yr OS 

FluMel 54% 

CyTBI 58% 

p=0.18 

5 yr DFS 

FluMel 50.8% 

CyTBI 54.9% 

p=0.07

  
NHL              
Rodriguez et al.r 88  

1 yr TRM

TBI-based/BuCy 33%

FluMel 28% 

p=0.40

2 yr relapse rate 

TBI-based/BuCy 13% 

FluMel 28% 

2 yr OS 

TBI-based/BuCy 52% 

FluMel 53% 

p=0.99 

2 yr PFS

TBI-based/BuCy 46% 

FluMel 40% 

p=0.46

  
Thomson et al.r 48   4 yr NRM 32% 

4 yr relapse risk 33% 

(occurring at median of 4 months)

4 yr OS 

47% overall 

54% if chemo sensitive

12% if chemo refractory 

p=0.016 

 4 yr PFS 48% overall   
Pinana et al.r 37   4 yr NRM 37% Relapse in 8% of patients at median 122 days

4 yr OS 57% overall

 4 yr DFS 55% overall   
HL              
Alvarez et al.r 40  

TRM 12% at day 100 

TRM 25% at 1 yr

   2 yr OS 48%  2 yr PFS 32%  
Anderlini et al.r 58  

TRM 7% at day 100 

TRM 15% at 2 yrs

   2 yr OS 64%  2 yr PFS 32%   
Chen et al.r 24  

NRM 4.2% at day 100 

NRM 13.1% at 1 yr

NRM 13.1% at 2 yrs

 2 yr relapse 63% at median 181 days till progression. 

1 yr OS 75% 

2 yr OS 60% 

1 yr PFS 50%

2 yr PFS 27% 

  
MM              
Sahebi et al.r 60  

NRM 10% at 1 yr

NRM 12% at 7 yrs

 7 yr relapse rate 67%  7 yr OS 42%  7 yr PFS 31%  
Shimoni et al.r  50  

NRM 26% at 5 yrs

(cumulative rate)

   7 yr OS 34%, with median survival 2.3yrs.   7 yr PFS 26%. PFS poorer if SD/PD at SCT, no cGVHD, female donor to male recipient, no CR achieved post SCT, and transplant >5yrs post diagnosis of MM. If none of these present, 7 yr PFS was 47%  
Kroger et al.r 49   NRM 25% at 1 yr

1 yr relapse incidence 17% 

3 yr relapse incidence 55% 

(18 deaths due to progression)

 5 yr OS 26%  5 yr PFS 20%  

NS = not significant

Toxicity

A summary of the toxicities associated with this protocol from the two largest studies are included in the table below: 

Study Mucositis

aGVHD

- gde 2 - 4

- gde 3/4 

cGVHD 

- total 

- extensive 

- limited

 Rejection VOD/SOS Lung/IPS Infection Comment
AML/MDS                
Baron et al.r -

Grade II: FluBu 14%, FluMel 16%

Grade III: FluBu 5%, FluMel 7%

Grade IV: FluBu 4%, FluMel 3%

cGVHD at 2yrs

FluBu 54% vs FluMel 48%

p=0.15

1.3% FluBu (n=3) 

0% FluMel

 -  - - -
Bryant et al.r -

Grade II-IV 

Lymphoid 47%

Myeloid 39%

Cumulative incidence of aGVHD total: 41%

cGVHD 70% at day 100 (in n=256 evaluable) 

Cumulative incidence of extensive cGVHD total: 34%

 - -  - - -

aGVHD = acute graft versus host disease; cGVHD = chronic graft versus host disease; VOD = veno-occlusive disease; SOS = sinusoidal obstruction syndrome; IPS = idiopathic pneumonia syndrome

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Version 6

Date Summary of changes
31/01/2024

Protocol assessed by eviQ BMT Reference Committee and deemed suitable to be reviewed as required. Flag added, review date removed and version number increased to V.6. Read more about as required review protocol status in this factsheet.
02/04/2024

Extravasation, tissue or vein injury added to side effects per updates to extravasation document.
25/11/2024

Flag added noting there is evidence to support the use of post-transplant cyclophosphamide (for GVHD prophylaxis) with this conditioning protocol. Link to ID 4428 GVHD prophylaxis Post-transplant cyclophosphamide (PTCy) protocol added.

Version 5

Date Summary of changes
16/05/2022 “Drug dosing in obese patients undergoing conditioning chemotherapy in BMT" block added to clinical information. Version number changed to v.5.
27/05/2022 Protocol title updated to reflect eviQ naming convention.
26/08/2022

Protocol reviewed electronically by BMT Reference Committee. Minor updates include: 

  • Added pre-transplant assessment flag and removed from Indications
  • Formatting in Dose Modifications
  • Minor grammatical changes

Review in 4 years
25/07/2023 Neurotoxicity added to "Late" category of Side effects section.
06/09/2023 EBV monitoring added to clinical information section.

Version 4

Date Summary of changes
31/05/2010 New protocol taken to HPCT Reference Committee meeting.
18/02/2011 Approved and published on eviQ.
12/04/2012 New format to allow for export of protocol information.
Protocol version number changed to V.2.
Antiemetics and premedications added to the treatment schedule.
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations.
Drug specific information placed behind the drug name link.
04/09/2012 Added note in the treatment schedule disclaimer to include the melphalan dilution concentration reference i.e. reached by group consensus.
27/05/2015 Ganciclovir removed from the treatment schedule, dose modifications and administering sections as per discussion at 2014 HPCT Reference Committee meeting.
29/04/2016 Reviewed at BMT Reference Committee meeting:
  • Non myeloablative removed from title
  • Added a note regarding ATG
  • Updated indications
  • Evidenced reviewed and updated
  • Version number changed to V.4.
31/05/2017 Transferred to new eviQ website.
15/01/2018  Wording of folinic acid rescue changed to “could be considered” from “should be given” as per reference committee consensus (BMT meeting September 2017). 
1/03/2019

Following discussions at the August 2018 BMT RCM, ACI 1608 HCT-CI (pdf) removed and links to the Fred Hutchinson Cancer Research Centre (FHCRC)  HCT Co-morbidity Index Calculator and CIBMTR Disease Risk Index (DRI) Assignment Tool added.
22/01/2021

Reviewed at BMT reference committee meeting July 2019. Approved for publication with the following changes:

  • Note under treatment schedule modified to add melphalan 120 mg/m2 dosing with references
  • Evidence updated, reformatted and information pertaining to non-malignant disorders removed 
  • For review in 4 years.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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