title: Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression.
abstract: OBJECTIVE
  To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure.
  
  
  BACKGROUND
  Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol ("Pittsburgh protocol").
  
  
  METHODS
  Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring.
  
  
  RESULTS
  All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates.
  
  
  CONCLUSIONS
  Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.
authors.affiliation: Department of Plastic and Reconstructive Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Gorantla
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: John G
authors.initials: JG
authors.lastname: Lunz
authors.forename: Diana M
authors.initials: DM
authors.lastname: Metes
authors.forename: Albert D
authors.initials: AD
authors.lastname: Donnenberg
authors.forename: Jaimie T
authors.initials: JT
authors.lastname: Shores
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Dimartini
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Kiss
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Imbriglia
authors.forename: Kodi
authors.initials: K
authors.lastname: Azari
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Goitz
authors.forename: Ernest K
authors.initials: EK
authors.lastname: Manders
authors.forename: Vu T
authors.initials: VT
authors.lastname: Nguyen
authors.forename: Damon S
authors.initials: DS
authors.lastname: Cooney
authors.forename: Galen S
authors.initials: GS
authors.lastname: Wachtman
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Keith
authors.forename: Derek R
authors.initials: DR
authors.lastname: Fletcher
authors.forename: Camila
authors.initials: C
authors.lastname: Macedo
authors.forename: Raymond
authors.initials: R
authors.lastname: Planinsic
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Starzl
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D005542:Forearm / Q000601:surgery*; D063987:Hand Transplantation; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus