title: Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.
  
  
  METHODS
  Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.
  
  
  RESULTS
  Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.
  
  
  CONCLUSIONS
  Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.
authors.affiliation: Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. j-winter@northwestern.edu
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: Stewart
authors.initials: S
authors.lastname: Spies
authors.forename: Gregory
authors.initials: G
authors.lastname: Wiseman
authors.forename: David
authors.initials: D
authors.lastname: Patton
authors.forename: William
authors.initials: W
authors.lastname: Erwin
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Rademaker
authors.forename: Bing Bing
authors.initials: BB
authors.lastname: Weitner
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: Williams
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Ivana
authors.initials: I
authors.lastname: Micallef
authors.forename: Jayesh
authors.initials: J
authors.lastname: Mehta
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmer
authors.forename: Arturo
authors.initials: A
authors.lastname: Molina
authors.forename: Christine A
authors.initials: CA
authors.lastname: White
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016393:Lymphoma, B-Cell / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D011034:Podophyllotoxin / Q000008:administration & dosage; D016499:Radioimmunotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D016879:Salvage Therapy / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003561:Cytarabine; C422802:ibritumomab tiuxetan; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine