Venous access
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Central venous access device (CVAD) is required to administer this treatment.
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Cytokine Release Syndrome/Infusion Reactions
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Potentially life-threatening cytokine release syndrome (CRS) has been reported in patients receiving haploidentical related-donor (HRD) haematopoietic stem cell transplantation (SCT).
Infusion reactions have also occurred and may be clinically indistinguishable from manifestations of CRS.
Serious adverse events include pyrexia, asthenia, headache, hypotension, elevated liver enzymes, total bilirubin increased, and nausea. In some cases, disseminated intravascular coagulation, capillary leak syndrome, and haemophagocytic lymphohistiocytosis/macrophage activation syndrome have been reported in the setting of CRS.
Patients should be closely monitored for signs or symptoms of these events.
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Antiemetics for multi-day protocols
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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.
Prior to each dose of total body irradiation, prophylaxis with a 5-HT3 receptor antagonist and dexamethasone 4 mg daily is recommended.
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.
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Proton pump inhibitor
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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.
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Drug dosing in obese patients undergoing conditioning chemotherapy in BMT
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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 for more information about dose adjustment of specific drugs in conditioning regimens in overweight and obese patients.
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Haemorrhagic cystitis associated with high dose chemotherapy
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Hydration regimen pre high dose cyclophosphamide or ifosfamide (as per local guidelines).
There is limited evidence and no consensus regarding hydration regimens and mesna dose, route or timing of administration.
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Mesna dosing and administration
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There is evidence supporting variations in mesna doses and administration timings, with no clear evidence that one particular regimen is superior to another. The eviQ mesna recommendations may be based upon the individual trial/study or reference committee consensus and provide guidance on one safe way to administer the protocol. Individual institutional policy may vary and should be evidence-based.
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SIADH associated with high dose cyclophosphamide
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Syndrome of inappropriate secretion of ADH (SIADH) is more commonly associated with high dose cyclophosphamide (doses greater than 50 mg/kg), such as doses used in conditioning regimens or post transplant for GVHD prophylaxis for blood and marrow transplant.
With administration of high dose cyclophosphamide, aggressive fluid regimens are given to promote the excretion of cyclophosphamide to prevent haemorrhagic cystitis. As a result, marked water retention and potentially fatal hyponatremia may occurr resulting in hyponatremia, dizziness, confusion or agitation, unusual tiredness or weakness.
The condition is self-limiting although diuretic therapy may be helpful in the situation when the patient has stopped urinating (especially if this occurs during the first 24 hours of cyclophosphamide therapy). Susceptible patients should be monitored for cardiac decompensation. The volume of IV hydration should be reduced if weight gain is excessive (1.5-2 kg) during hydration.
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GVHD prophylaxis
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High dose cyclophosphamide (day +3 and +4), tacrolimus and mycophenolate mofetil (MMF).
Commence IV tacrolimus daily on day +5, 24 hours following the last dose of post-transplant cyclophosphamide. Adjust dose according to trough levels (target level = 5 to 15 ng/mL). In the absence of GVHD and FULL donor chimerism, cease without tapering at day +180.
Commence PO mycophenolate mofetil (MMF) THREE times daily on day +5, 24 hours following the last dose of post-transplant cyclophosphamide. In the absence of GHVD cease without tapering at day +35
If tacrolimus is stopped, the dose of MMF may need adjustment (reduced). The value of MMF blood levels are the subject of ongoing study.
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CMV pre-transplant prophylaxis
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In patients at high risk of CMV reactivation consider CMV prophylaxis. Practice may differ between institutions.
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EBV monitoring
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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.
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SOS prophylaxis
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Stratify according to risk profile.
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Tumour lysis risk
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Assess patient for risk of developing tumour lysis syndrome.
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Pneumocystis jirovecii pneumonia (PJP) prophylaxis
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PJP prophylaxis is recommended.
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Antiviral prophylaxis (HSV)
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Antiviral prophylaxis is recommended.
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Antifungal prophylaxis
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Antifungal prophylaxis is recommended.
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Growth factor support
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Consider the use of filgrastim from day +5 until recovery
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Blood product support
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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.
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Blood tests
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FBC, EUC, eGFR and LFTs are required each day. Fasting glucose should be assessed regularly.
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Hepatitis B screening and prophylaxis
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Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.
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Vaccinations
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Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.
Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.
Read more about COVID-19 vaccines and cancer.
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Fertility, pregnancy and lactation
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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 foetal 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.
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