High-dose yttrium-90-ibritumomab tiuxetan with tandem stem-cell reinfusion: an outpatient preparative regimen for autologous hematopoietic cell transplantation.
OBJECTIVE
To develop high-dose myeloablative therapy for CD20(+) non-Hodgkin's lymphoma (NHL) as a safe and widely applicable regimen.


METHODS
Patients with relapsed/refractory (n = 25) or de novo high-risk (n = 5) NHL received one myeloablative dose of yttrium-90 ((90)Y)-ibritumomab tiuxetan after five chemotherapy courses, including three cycles of anthracycline- or platinum-containing regimens, one cycle of cyclophosphamide (4 to 7 g/m(2)), and one cycle of cytarabine (12 to 24 g/m(2)). The only exclusion criteria were CNS lymphoma and Eastern Cooperative Oncology Group performance status of more than 3. Primary end points were overall survival (OS) and event-free survival (EFS). Secondary end points included safety and applicability of high-dose (90)Y-ibritumomab tiuxetan. To minimize hematologic toxicity, stem cells were reinfused at days 7 and 14 after (90)Y-ibritumomab tiuxetan.


RESULTS
Thirteen patients received (90)Y-ibritumomab tiuxetan 0.8 mCi/kg, and 17 patients received 1.2 mCi/kg. At 1.2 mCi/kg, the radiation absorbed by critical nonhematologic organs approached the protocol-defined upper safety limit, defining this as the recommended dose for subsequent studies. Hematologic toxicity was mild to moderate and of short duration. Infections occurred in 27% of patients (none had a severity grade greater than 3). After a median observation time of 30 months (range, 22 to 48 months), no myeloid secondary malignancy or chromosomal abnormality was observed, the OS rate was 87%, and the EFS rate was 69%.


CONCLUSIONS
High-dose (90)Y-ibritumomab tiuxetan seems to be an innovative myeloablative regimen with unprecedented short-term toxicity and wide applicability. Further studies are required to assess its long-term safety and role in the management of CD20(+) NHL.
Cristina Gandini Medical Oncology and Department of Nuclear Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milan, Italy.
Liliana
L
Devizzi
Anna
A
Guidetti
Corrado
C
Tarella
Michele
M
Magni
Paola
P
Matteucci
Ettore
E
Seregni
Carlo
C
Chiesa
Emilio
E
Bombardieri
Massimo
M
Di Nicola
Carmelo
C
Carlo-Stella
Alessandro M
AM
Gianni
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; C422802:ibritumomab tiuxetan