Transplant Strategies For The Initial Management Of Mantle Cell Lymphoma: A Single Institution Analysis
Authors: Adeimy Camille , Kobrinski Daniel , Stiff Patrick J , Rodriguez Tulio E. , Go Aileen , Parthasarathy Mala , Smith Scott E. 
Published: October 2019

Abstract
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin’s lymphoma (NHL) characterized by the chromosomal translocation t (11;14) (q13;q32). It comprises approximately 6% of all NHL, but has a highly aggressive clinical course. While 60-90% of patients achieve complete remission (CR) with augmented induction regimens, approximately 85% will eventually relapse with a median overall survival (OS) of 3-4 years with less than 15% of patients alive at 5 years. Optimal initial therapy for this disease usually includes for those in first CR autologous hematopoietic stem cell transplant (HSCT), with allogeneic HSCT reserved for those who relapse. Patients who are non-responsive to first-line chemotherapy are increasingly being considered for an allogeneic HSCT.

Methods
After obtaining IRB approval, a retrospective chart review was performed on all patients with a diagnosis of MCL (confirmed by histology) at LUMC to compare the outcome of transplants vs. non-transplants patients. Primary end points were overall survival (OS) and progression-free survival (PFS) after stem cell transplant. A total of 104 patients were evaluated from 1999 to 2013, of whom 63 underwent a transplant after induction therapy and 13 an allograft after first relapse.

Results
The induction chemotherapy regimens used for the 104 patients were CHOP(R) in approximately 50% and Hyper-CVAD in 25%. A total of 51 patients received a first remission autologous HSCT, of these 20 patients were in CR1 at the time of transplant. A total of 25 patients received an allogeneic transplants (15 were sibling and 10 unrelated grafts); 12 underwent first-line allogeneic transplant with 65% receiving a reduced intensity regimen. In the group of 13 patients who relapsed after autologous HSCT, 90% received a reduced intensity regimen. Survival analysis by treatment modality was as follows: median OS for the non-transplant and transplant cohorts respectively were 29 months and 63.5 months (p=0.007). Median OS was not reached for patient who received first-line allogeneic HSCT while median OS for patient failing a prior autologous HSCT who received an allogeneic transplant was 28 months.
Of the 12 patients who underwent first-line allogeneic transplant, despite all having chemo-resistant disease after induction therapy, no patient died of relapse; the only patient who relapsed received bortezomib and rituximab and achieved complete remission.
Of the 13 patients who received an allogeneic transplant after prior autologous transplant, only two patients died of relapsed disease but nine patients died of transplant-related complications, largely related to their poor performance status due to multiple chemotherapy regimens associated with their refractory lymphoma.

Conclusions
Our results for autografts are consistent with the data available in the literature confirming the benefit of this strategy as part of induction treatment. However this analysis suggests a significant benefit for early allografts for those failing induction therapy, presumably due to a potent graft vs. lymphoma effect despite chemotherapy resistance. Such an effect also occurs for allografts performed after autograft failure, but the frailty of patients does impact its benefit. Based on our data, patients in CR1 should be considered for ASCT after initial therapy, however those in less than CR after initial therapy should be considered for an early allogeneic transplant.

Disclosures:
No relevant conflicts of interest to declare.