Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosage.
BACKGROUND
Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure.


METHODS
Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure.


RESULTS
Mean BU exposure (AUCss) (+/-DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade > or = II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT.


CONCLUSIONS
The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD.
Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. aclopes@iconcologia.net
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Clopés
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Sureda
J
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Sierra
J M
JM
Queraltó
A
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Broto
R
R
Farré
E
E
Moreno
S
S
Brunet
R
R
Martino
M A
MA
Mangues
D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D002423:Cause of Death; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009101:Multiple Myeloma / Q000150:complications / Q000628:therapy*; D012074:Remission Induction; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
D002066:Busulfan