title: Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin's lymphoma treated with high-activity myeloablative 90Y-ibritumomab tiuxetan (Zevalin).
abstract: OBJECTIVE
  The aim of this study was to carry out two different dose estimation approaches in patients with non-Hodgkin's lymphoma (NHL) treated with a myeloablative amount of (90)Y-labelled ibritumomab tiuxetan (Zevalin(R)) in an open-label dose escalation study.
  
  
  METHODS
  Twenty-seven patients with relapsed/refractory or de novo high-risk NHL receiving one myeloablative dose of (90)Y-ibritumomab tiuxetan followed by tandem stem cell reinfusion were evaluated for dose estimate. The injected activity was 30 MBq/kg in 12 patients and 45 MBq/kg in 15 patients. Dose estimation was performed 1 week prior to (90)Y-ibritumomab tiuxetan by injection of (111)In-ibritumomab tiuxetan (median activity: 200 MBq). The absorbed dose (D) and the biologically effective dose (BED) were calculated.
  
  
  RESULTS
  The absorbed doses per unit activity (Gy/GBq) were [median (range)]: heart wall 4.6 (2.5-9.7), kidneys 5.1 (2.8-10.5), liver 6.1 (3.9-10.4), lungs 2.9 (1.5-6.8), red marrow 1.0 (0.5-1.7), spleen 7.0 (1.5-14.4) and testes 4.9 (2.9-16.7). The absorbed dose (Gy) for the 15 patients treated with 45 MBq/kg were: heart wall 17.0 (8.7-25.4), kidneys 17.1 (7.9-22.4), liver 20.8 (15.4-28.3), lungs 8.1 (5.4-11.4), red marrow 3.1 (2.0-4.0), spleen 26.2 (17.0-35.6) and testes 17.3 (9.0-28.4). At the highest activities the acute haematological toxicity was mild or moderate and of very short duration, and it was independent of the red marrow absorbed dose. No secondary malignancy or treatment-related myelodysplastic syndrome was observed. No non-haematological toxicity (liver, kidney, lung) was observed during a follow-up period of 24-48 months.
  
  
  CONCLUSIONS
  The use of 45 MBq/kg of (90)Y-ibritumomab tiuxetan in association with stem cell autografting resulted in patients being free of toxicity in non-haematological organs. These clinical findings were in complete agreement with our dose estimations, considering both organ doses and BED values.
authors.affiliation: Nuclear Medicine Division, Foundation IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy. carlo.chiesa@istitutotumori.mi.it
authors.forename: C
authors.initials: C
authors.lastname: Chiesa
authors.forename: F
authors.initials: F
authors.lastname: Botta
authors.forename: A
authors.initials: A
authors.lastname: Coliva
authors.forename: M
authors.initials: M
authors.lastname: Maccauro
authors.forename: L
authors.initials: L
authors.lastname: Devizzi
authors.forename: A
authors.initials: A
authors.lastname: Guidetti
authors.forename: C
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: E
authors.initials: E
authors.lastname: Seregni
authors.forename: M A
authors.initials: MA
authors.lastname: Gianni
authors.forename: E
authors.initials: E
authors.lastname: Bombardieri
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001853:Bone Marrow / Q000528:radiation effects; D002138:Calibration; D005260:Female; D015902:Gamma Cameras; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy; D008297:Male; D011829:Radiation Dosage; D011874:Radiometry; D011879:Radiotherapy Dosage; D012306:Risk; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; C422802:ibritumomab tiuxetan