Allogeneic hematopoietic transplantation for mantle-cell lymphoma: Molecular remissions and evidence of graft-versus-malignancy

Background: The presence of a graft-versus-tumor effect has been well estab lished for various hematological malignancies but not for mantle-cell lymph oma (MCL). We report preliminary results suggestive of a graft-versus-lymph oma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL receive d allogeneic transplantation. Three had blastic features. Fifteen had an HL A-identical and one, a one HLA antigen mismatched sibling donor. Fifteen ha d stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagn osed and received transplantation after cytoreduction with three to eight c ourses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristi ne, 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 p atients were not eligible for TBI and received the BEAM regimen. Twelve (85 .7%) achieved complete and two (14.3%) partial response. Two additional pat ients received a nonablative preparative regimen consisting of cisplatin, c ytarabine and fludarabine. One failed to engraft and later relapsed. The ot her patient had progressive disease one month post transplant but later ach ieved complete remission now durable for 14+ months after developing graft- versus-host disease (GVHD). Residual lymphoma was assessed in seven patient s by polymerase chain reaction assay (PCR) forbcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When t ested within four months post transplant, four of these patients attained m olecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positiv e and negative PCR fourteen months post transplant. Overall survival (OS) a nd failure-from-progression (FFP) at three years were both 55% (95% confide nce 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 ch emotherapy at the time of transplantation. There were six deaths. These wer e 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 sugge stive of graft-versus-malignancy in MCL. Data supportive of this concept in clude 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status ov er time and 3) that the only relapse was in a patient who failed to engraft .