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. PATIENTS AND 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.

Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study.

We investigated whether daily oral washings with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) solution improved grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Forty-one consecutive patients (21 males and 20 females, median age (range) 44 (16-69) years) were prospectively randomized to perform daily mouth-washes with either a 400 microg rhGM- CSF (Molgramostin, Schering-Plough) solution (group A, n = 18) or with a saline solution (group B, n = 23). Primary end-points were the intensity of OM, night rest quality and characteristics of food intake. Secondary end-points were need for and duration of parenteral nutrition, oral and intravenous analgesic requirements, incidence of viral or fungal oral infections and development of neutropenic fever. No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM, maximum grade, reduction in at least one grade of OM (nine patients (56%) in group A vs 13 patients (68%) in group B), reduction of spontaneous or swallowing-induced pain, improvement in oral food intake, use of parenteral nutrition or use of systemic analgesics. In conclusion, mouth-washings with a 400 microg of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation.

[Hematopoietic allogeneic transplantation with attenuated conditioning regimen on an outpatient basis. First experience in Spain]. / Trasplante alogénico de progenitores hematopoyéticos con acondicionamiento no mieloablativo en régimen ambulatorio. Primera experiencia en España.

BACKGROUND: Allogeneic hematopoietic transplantation using attenuated conditioning regimens seems promising. This procedure associates to relatively low morbidity and mortality. In consequence, an outpatient management of this transplantation modality may be considered, even in elderly patients. CLINICAL REPORT AND RESULTS: This approach was considered in a 62 years-old female suffering from chronic myeloid leukemia in chronic phase. The conditioning regimen included fludarabine and 200 cGy of total body irradiation. Cyclosporine A and mycophenolate mofetil were used as immunosuppression. Conditioning, peripheral-blood stem-cell infusion, and postransplant follow-up was managed in the outpatient setting. Two short admissions were required. Eight months after transplant, the patient remains in sustained haematological remission with complete donor chimerism,has a 100% Karnofsky score and continues being managed on an outpatient basis. CONCLUSIONS: Allogeneic stem-cell transplantation can be performed safely on an outpatient basis,even in elderly patients.