title: Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation.
abstract: Allogeneic donor leukocytes can be used after nonmyeloablative conditioning to exploit their graft-versus-tumor (GVT) activity in the setting of reduced conditioning-regimen toxicity. This approach may be particularly useful for patients who relapse after autologous stem cell transplantation (SCT). However, GVT activity, toxicity, and ability to establish mixed chimerism may differ in patients who were heavily pretreated prior to SCT compared with patients treated earlier in the course of their disease. We have performed a series of studies of nonmyeloablative allogeneic transplantation and present data on the subset of 14 patients treated for relapse after autologous SCT: 4 patients received no conditioning and unstimulated donor leukocyte infusions (DLI), 10 patients received conditioning with fludarabine and cyclophosphamide followed by unstimulated or granulocyte-colony-stimulating factor (G-CSF)-stimulated allogeneic peripheral blood stem cells (PBSCs), 4 patients received no graft-versus-host disease (GVHD) prophylaxis, and 10 patients received cyclosporine GVHD prophylaxis. All but 1 patient had sustained donor chimerism at least 30 days after allogeneic cell therapy (ACT), and 8 patients had more than 80% donor chimerism after ACT. Acute GVHD developed in 11 patients (grade III-IV, n = 6). Aplasia was more frequent in the patients receiving unstimulated PBSCs, despite the development of mixed chimerism. There were 6 complete responses and 4 partial responses; response was independent of conditioning and growth-factor stimulation of the donor graft. Five patients died of treatment-related causes and 4 patients died from progressive disease. Four patients remained alive 27 to 194 weeks (median, 66 weeks) after ACT. Prior autologous SCT may define a subset of patients at particularly high risk for GVHD and other toxicity after ACT. However, these data show that ACT with either DLI or G-CSF-stimulated blood cells results in direct GVT activity in some patients with Hodgkin's disease, myeloma, and non-Hodgkin's lymphoma, even after relapse from autologous SCT. Most patients developed donor chimerism with minimal conditioning. Alternative prophylactic regimens that control GVHD while maintaining GVT are needed to improve outcomes in these heavily pretreated patients.
authors.affiliation: Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Medical Center, Philadelphia 19104, USA. david.porter@uphs.upenn.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Porter
authors.forename: S M
authors.initials: SM
authors.lastname: Luger
authors.forename: K M
authors.initials: KM
authors.lastname: Duffy
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: G
authors.initials: G
authors.lastname: Laport
authors.forename: S J
authors.initials: SJ
authors.lastname: Schuster
authors.forename: G
authors.initials: G
authors.lastname: Orloff
authors.forename: D
authors.initials: D
authors.lastname: Tsai
authors.forename: K
authors.initials: K
authors.lastname: McDaid
authors.forename: A
authors.initials: A
authors.lastname: Kathakali
authors.forename: D G
authors.initials: DG
authors.lastname: Leonard
authors.forename: J H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002678:Chimera; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D020350:Graft vs Tumor Effect; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000628:therapy; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007239:Infections / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000401:mortality; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine