Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma: A Retrospective Study of the Geltamo Group (1994-2011)
Authors: García-Noblejas Ana , Conde Eulogio , Martín Alejandro , Vidal María Jesús , Rojas Rafael , Grande Carlos , Ramirez María José , Cannata-Ortiz Jimena , García-Ruiz Juan Carlos , Briones Javier , Lopez Andrés , Ríos Rull Pablo , Noriega Victor , Deben Guillermo , González Barca Eva , González de Villambrosia Sonia , Ferreiro Jose Javier , Lahuerta Juan José , Caballero Maria Dolores , Arranz Reyes 
Published: October 2019

Abstract
INTRODUCTION
Autologous stem cell transplantation (ASCT) is one of the current treatment options for first-line treatment of mantle cell lymphoma (MCL) in young and fit patients in first complete response (CR). Nevertheless its role in less than CR, after intensive chemotherapy schemas or as consolidation after salvage regimens has not been established.
AIM
To analyze the impact of patient and treatment characteristics on outcome of MCL patients treated with ASCT.
METHODS
Retrospective analysis of MCL patients treated with ASCT and registered in the GELTAMO database from 1994 to 2011. An outcome up-date was performed on December 2013. The study was approved by local ethical committees. Statistical analysis was performed using SPSS 15.0.
RESULTS
Two hundred and forty eight patients were registered from the GELTAMO database.
Patients’characteristics : median age was 55 years old (range 21-70 y), 70% male. One hundred and fifty eight patients (68%) were transplanted in CR, 125 were in first CR (79% of all CR) and 33 in second or third CR (21%). Fifty two patients (22%) were transplanted in first partial response and 15 (6%) with chemosensitivity disease after relapse. Only 8 patients (3%) were transplanted with refractory disease.
Response : forty-eight out of 75 patients (64%) without CR at ASCT converted to CR after transplant.
Survival: Sixteen percent of patients were lost to follow-up one year after transplantation. Median follow-up for alive patients was 47 months (range 0-245 months). Progression free survival for patients transplanted in first CR was 45 months (CI95%: 33-56 months), for patients transplanted in first partial response (PR) was 28 months (CI95%: 15-21months) and for patients transplanted in other response was 19 months (CI95%: 12-26 months). In the whole series, median overall survival (OS) from transplantation was 69 months (CI95% 51-87 months) and for those patients transplanted in first CR was 98 months (CI95% 67-130 months). When patients without CR before transplant are analyzed separately, those who achieved CR after transplantation have better PFS (38 vs 10 months, p<0.001) and OS (74 vs 16 months, p<0.001) than others. Treatment related mortality was 4%.
We analyzed the variables that could be associated with PFS and OS. We considered age (≤60 vs >60), ECOG (<2, ≥2), IPI (<2, ≥2), status at transplant (1st CR vs others), conditioning with TBI and HDAC in first line treatment. In univariate analysis, ECOG (p=0.04) and status at transplant (p=0.01) were the variables associated with PFS. For OS, the same variables resulted significant (p<0.001 and p=0.07, respectively) and also, HDAC emerged as significant variable associated with outcome. (p=0.05). In multivariate analysis, ECOG and status at transplant remained as independent prognostic factors for PFS while ECOG and HDAC in first line had impact for OS, see Table 1.
Table 1. Variables identified as independent prognostic factors for PFS and OS in multivariate analysis. PFS OS p RR (95% CI) p RR ECOG 0.01 3.6 (1.3-9.9) 0.04 4.5 (1.6-12.5) Status at trasplant 0.03 1.4 (1-2) 0.09 (ns) ---- HDAC at 1st line 0.7 (ns) ---- 0.014 0.5 (0.3-0.8)
Afterwards, a survival analysis for PFS and OS was performed according to have received high dose AraC (HDAC) in first line treatment or not and disease status (DS) before ASCT (Table 2).
Table 2. Survival analysis according to have received HDAC in 1st line treatment and disease status (DS) before ASCT DS before ASCT N Firts line treatment N PFS (CI95%)(Kaplan Meier) p OS (CI95%)(Kaplan Meier) p 1st CR 125 No HDAC 52 37 (22-51) 0.13 64 (37-91) 0.01 HDAC 72 56 (33-78) No reached 1st PR 52 No HDAC 35 33 (3-63) 0.59 61 (0-126) 0.9 HDAC 17 27 (18-37) 69 (46-92) ≠1st CR/PR 51 No HDAC 46 20 (13-27) 0.16 35 (5-66) 0.9 HDAC 5 11 (7-16) No reached
CONCLUSION
This retrospective study reproduces previous results published about the role of ASCT in MCL: ASCT consolidation in first CR induces high survival rates with a median PFS of 45 months and median OS of 98 months. Patients without CR after ASCT had a significant inferior outcome. ECOG < 2 and status at transplantation are crucial for PFS and first line treatment with AraC improves significantly OS, particularly in patients with first CR.

Disclosures
No relevant conflicts of interest to declare.