Regimen: Relapsed/Refractory Multiple Myeloma: Conditioning Regimen Before Autologous Peripheral Blood Stem Cell Transplantation: High-Dose Melphalan
Moreau P et al. Blood 2002;99:731–735
Conditioning for autologous PBSC transplant:
Melphalan 200 mg/m2; administer intravenously, diluted in sufficient 0.9% sodium chloride injection (0.9% NS) to produce a concentration ≤0.45 mg/mL over 30 minutes, 2 days before PBSC reinfusion (on day −2) (total dosage = 200 mg/m2). PBSC reinfusion on day 0 (zero), or
Melphalan 100 mg/m2 per day; administer intravenously, diluted in sufficient 0.9% NS to produce a concentration ≤0.45 mg/mL over 30 minutes, for 2 consecutive days, starting 3 days before PBSC reinfusion (on days −3 and −2) (total dosage = 200 mg/m2). PBSC reinfusion on day 0 (zero)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential is HIGH on days melphalan is administered. Potential for delayed symptoms
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Filgrastim (G-CSF), 5–10 mcg/kg per day; administer by subcutaneous injection starting on day +7 after PBSC reinfusion, and continue until granulocyte counts recover, or
Sargramostim (GM-CSF) 5–10 mcg/kg per day; administer by subcutaneous injection starting on day +7 after PBSC reinfusion, and continue until granulocyte counts recover
Antimicrobial prophylaxis
Antibacterial prophylaxis (P. jirovecii pneumonia prophylaxis):
Trimethoprim + Sulfamethoxazole (TMP + SMZ) 160 mg/800 mg; administer orally, daily, continually for 3 months, or
TMP + SMZ 80 mg/400 mg; administer orally daily, continually for 3 months, or
TMP + SMZ 160 mg/800 mg; administer orally 3 days per week, continually for 3 months
Antifungal prophylaxis
Fluconazole 200–400 mg/day; administer orally or intravenously daily for 30 days after PBSC reinfusion or until neutrophil engraftment occurs (ANC >500/mm3)
Antiviral prophylaxis for HSV-seropositive recipients to prevent reactivation of HSV during the early posttransplant period
Acyclovir 200 mg; administer orally every 8 hours for 30 days, or
Acyclovir 250 mg/m2 per dose; administer intravenously every 12 hours for 30 days, or
Valacyclovir 500 mg; administer orally daily for 30 days
Note: Routine acyclovir prophylaxis for >30 days after HSCT is not recommended
Caution: Acyclovir and famciclovir accumulate in patients with impaired renal function and may exacerbate renal dysfunction (valacyclovir is a prodrug for acyclovir). Monitor kidney function serially during acyclovir, valacyclovir, and famciclovir use
Acyclovir and famciclovir elimination is inversely related to renal function
Acyclovir, famciclovir, and valacyclovir utilization is modified in renally impaired individuals (consult product labeling or Summary of Product Characteristics for guidance about dose/dosage and administration frequency modifications, and, when relevant, recommendations for drug dilution, administration rate, concurrent fluid administration, and fluid supplementation as a function of urine output)
Impaired acyclovir elimination is associated with neurologic adverse effects, including agitation, ataxia, coma, confusion, dizziness, dysarthria, encephalopathy, hallucinations, paresthesia, seizure, somnolence, and tremors
See Chapter 47 for more information
Oral care
Prophylaxis and treatment for mucositis/stomatitis
General advice:
Encourage patients to maintain intake of non-alcoholic fluids
Evaluate patients for oral pain and provide analgesic medications
Consider histamine H2-receptor antagonists (eg, ranitidine, famotidine), or a proton pump inhibitor for epigastric pain
Lactobacillus sp.-containing probiotics may be beneficial in preventing diarrhea
Patients with intact oral mucosa:
Clean the mouth, tongue, and gums by brushing after every meal and at bedtime with an ultra-soft toothbrush with fluoride toothpaste
Floss teeth gently every day unless contraindicated. If gums bleed and hurt, avoid bleeding or sore areas, but floss other teeth
Patients may use saline or commercial bland, non-alcoholic rinses
If mucositis or stomatitis is present:
Keep the mouth moist utilizing water, ice chips, sugarless gum, sugar-free hard candies, or a saliva substitute
Rinse mouth several times a day to remove debris
Use a solution of ¼ teaspoon (1.25 g) each of baking soda and table salt (sodium chloride) in one quart (~950 mL) of warm water. Follow with a plain water rinse
Do not use mouthwashes that contain alcohols
Foam-tipped swabs (eg, Toothettes) are useful in moisturizing oral mucosa, but ineffective for cleansing teeth and removing plaque
Advise patients who develop mucositis to:
Choose foods that are easy to chew and swallow
Take small bites of food, chew slowly, and sip liquids with meals
Encourage soft, moist foods such as cooked cereals, mashed potatoes, and scrambled eggs
For trouble swallowing, soften food with gravies, sauces, broths, yogurt, or other bland liquids
Avoid sharp, crunchy foods; hot, spicy or highly acidic foods (eg, citrus fruits and juices); sugary foods; toothpicks; tobacco products; alcoholic drinks
Notes:
This conditioning regimen was part of a more comprehensive therapy for multiple myeloma that included the following:
Before PBSC harvest, patients received 3 cycles of vincristine + doxorubicin + dexamethasone (VAD)
In the absence of tumor progression (>25% increase in tumor mass), and if cardiopulmonary, hepatic, and renal function (serum creatinine <1.7 mg/dL [<150 μmol/L]) remained adequate after a third course of VAD, peripheral blood stem cells (PBSCs) were collected
After PBSC collection, patients received a fourth course of VAD
4. After completion of high-dose chemotherapy (HDT) and PBSCT, treatment with recombinant interferon alfa 3 million International Units was given by subcutaneous injection 3 times weekly after granulocytes exceeded 1500/mm3 and platelets exceeded 100,000/mm3 during the first year after transplantation. Interferon was continued at participating physicians' discretion in case of disease progression or when it induced severe and persistent adverse effects. The value of maintenance interferon in this or any setting is uncertain
Patient Population Studied
A study of 142 patients ≤65 years of age with symptomatic multiple myeloma responding to primary chemotherapy with VAD
Exclusions:
Stable stage 1 MM deemed not to require therapy (Durie-Salmon classification)
Previous cytotoxic chemotherapy other than VAD in preparation for transplantation✫
Previous radiation therapy
Severe abnormalities of cardiac, pulmonary, and hepatic function (not characterized)
Serum creatinine concentration >5.7 mg/dL (>504 μmol/L)
Therapy Monitoring
CBC with differential, daily to every third day as hematological recovery occurs