Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation for Adults with Relapsed and Refractory Mantle Cell Lymphoma: A Single Center Retrospective Analysis in the Rituximab Era

Backgrounds: Despite recent improvements in the therapy of mantle cell lymphoma, relapsed and refractory disease still portends a dismal prognosis. Allogeneic stem cell transplantation (allo-SCT) represents the only potentially curative therapy in this setting. The aim of this report was to evaluate the results of reduced-intensity-conditioning (RIC) allo-SCT in a retrospective cohort of patients from a single institution.

Patients and methods: Twenty-nine patients (median age 58 years, range 34-71) undergoing RIC allo-SCT from April 1999 to May 2013 are included in this retrospective analysis.  The median number of previous lines of therapy was 5 (range 1-6) with 13 (45%) of patients having previously failed an autologous SCT.  Twenty-six patients (90%) had chemosensitive disease at allo-SCT (CR=17, PR=9) and 3 (10%) had stable disease.  The second line International Prognostic Index (sIPI) was 0 in 19 patients (65%) and ≥1 in 9 patients (31%). Data was missing in 1.  RIC regimens included cyclophosphamide/ fludarabine/ TBI 200cGy with (n=17) or without (n=4) peri-allo-SCT rituximab and melphalan/ fludarabine with (n=6) or without (n=2) alemtuzumab. All patients received unmodified grafts from a matched related (n=12), matched unrelated (n=10) or mismatched unrelated (n=7) donor.  Progression-free (PFS) and overall (OS) survival were calculated from the time of allo-SCT. Kaplan-Meier survival curves and a permutation-based logrank test were used to compare PFS and OS based on alemtuzumab use and the sIPI.

Results: All but one patient engrafted with full donor chimerism.  The cumulative incidences (CI) of grade II-IV acute GVHD at days +100 and +180 were 36% (95%CI: 19-53%) and 46% (95%CI: 27-64%), respectively.  The CI of chronic GVHD at 1 and 2 years was 20% (95%CI: 7-38%) and 29% (95%CI: 12-49%), respectively.  The CI of progression of disease and non-relapse mortality at 2 years were 32% (95%CI: 15-51%) and 19% (95%CI: 7-37%), respectively.  With a median follow-up in survivors of 40 months (range 2-80 months), the 2-year OS and PFS are 64% (95%CI: 47-86%) and 49% (95%CI: 32-73%), respectively.  In vivo T cell-depletion with alemtuzumab was associated with a markedly reduced 2-year PFS (0% vs 64%, p=0.008) (Figure 1).  Conversely, a sIPI at transplantation <1 was associated with a much improved 2-year PFS (65% vs 13%, p=0.021) compared to higher sIPI values (Figure 2). Similarly, 2-year OS was also significantly reduced with alemtuzumab (33% vs 74%, p=0.016) and in patients with sIPI ≥1 (39% vs 76%, p=0.036).

Conclusions: RIC allo-SCT is a feasible and effective strategy in patients with relapsed and refractory mantle cell lymphoma.  High sIPI and use of alemtuzumab in the conditioning regimen are associated with markedly inferior PFS.  Higher risk disease and the likely loss of graft-versus-lymphoma with alemtuzumab predict likelihood of failure of RIC allo-SCT in relapsed and refractory MCL patients.