title: Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.
abstract: BACKGROUND
  The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation.
  
  
  METHODS
  Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine.
  
  
  RESULTS
  Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%-100%) compared with 44% (95% CI: 1%-88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case).
  
  
  CONCLUSIONS
  This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.
authors.affiliation: Department of Blood and Marrow Transplantation, University of Texas, M.D. Anderson Cancer Center, Houston, USA. ikhouri@notes.mdacc.tmc.edu
authors.forename: I F
authors.initials: IF
authors.lastname: Khouri
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Romaguera
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: M
authors.initials: M
authors.lastname: Albitar
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: B
authors.initials: B
authors.lastname: Samuels
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: J
authors.initials: J
authors.lastname: Rodriguez
authors.forename: B
authors.initials: B
authors.lastname: von Wolff
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: R
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001483:Base Sequence; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D018709:Statistics, Nonparametric; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome