Abstract Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients.
Ann Hematol DOI 10.1007/s00277-013-1860-8
ORIGINAL ARTICLE
Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC Cyrille Touzeau & Christophe Leux & Reda Bouabdallah & Murielle Roussel & Richard Delarue & Krimo Bouabdallah & Catherine Thieblemont & Victoria Cacheux & Guillaume Cartron & Laetitia Compain & Emmanuel Gyan & Franck Morschhauser & Olivier Casasnovas & Marie-Pierre Moles & Anne-Sophie Michallet & Remy Gressin & Gandhi Damaj & Christian Rose & Anne Sirvent & Olivier Hermine & Mohamad Mohty & Noel Milpied & Steven Le Gouill Received: 17 April 2013 / Accepted: 22 July 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n=396). For all patients, median age at ASCT was 56 years (range, 26–
C. Touzeau : S. Le Gouill Department of Hematology, University Hospital, Nantes, France C. Touzeau : S. Le Gouill INSERM UMR 892, University of Nantes, Nantes, France C. Touzeau : S. Le Gouill Clinical Investigation Unit, University Hospital, Nantes, France C. Leux Department of Epidemiology and Biostatistics, University Hospital, Nantes, France R. Bouabdallah Institut Paoli Calmette, Marseille, France M. Roussel Department of Hematology, University Hospital, Toulouse, France R. Delarue : O. Hermine Department of Hematology, University Hospital Necker, Paris, France K. Bouabdallah : N. Milpied Department of Hematology, University Hospital, Bordeaux, France C. Thieblemont Department of Hematology, University Hospital Saint Louis, Paris, France C. Thieblemont Inserm U728, University of Paris, Paris, France
71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR=2 [1.2–3.4], p=.01, and HR=2.3 [1.2–4.5], p=.01), disease status at time of ASCT
V. Cacheux Department of Hematology, University Hospital, Clermont-Ferrand, France G. Cartron Department of Hematology, University Hospital, Montpellier, France L. Compain Department of Hematology, University Hospital Pitié-Salpêtrière, Paris, France E. Gyan Department of Hematology, University Hospital of Tours, Tours, France E. Gyan CIC INSERM U202, CNRS UMR 7292, University of Tours, Tours, France F. Morschhauser Department of Hematology, University Hospital of Lille, Lille, France O. Casasnovas Department of Hematology, University Hospital of Dijon, Dijon, France M.50 % reduction of tumor burden. Progressive disease (PD) was defined by >25 % increase of tumor mass. Remaining cases were scored as stable disease (SD) [19]. The study was approved by the SFGM-TC scientific council and performed according to SFGM-TC guidelines and in accordance with the declaration of Helsinki. Statistical methods Data were updated as of March 2011. PFS was calculated from diagnosis to the first event defined as relapse, progression, or death from any cause. OS was calculated from diagnosis to death. PFS and OS were calculated using the Kaplan–Meier method estimates and the differences assessed by the log-rank test. Continuous variables were separated into two levels according to the median value. All p values were two-sided and the 0.05 level was considered statistically significant. Variables found to be statistically significant at the p30 % in 35 (53 %) cases.
Table 1 Patient characteristics
Number of patients Male/female Median age at diagnosis (range) Median age at ASCT (range) Time of ASCT Before 2003 From 2003 to 2005 >2005 Blastoid variant Yes No Missing KI67 90 %) at time of transplantation. After ASCT, 369 patients achieved CR/CRu (74 %). ASCT increased the percentage of CR/CRu for more than 20 % of the patients. Various conditioning regimens were used. Conditioning regimens could be divided into two groups according to use of TBI or not. Two hundred and twenty-five (45 %) patients received a TBI-based conditioning regimen including TBI plus HD-Arac and melphalan (TAM; n=68), TBI plus cyclophosphamide (TBI/Cy; n=94) or TBI plus melphalan (TBI/ Mel; n=51), and missing data (n=12). Two hundred seventythree patients received a conditioning regimen without TBI, mainly the BEAM regimen (carmustine–etoposide– cytarabine–melphalan; n=215). PFS and OS Median FU was 34 months (range, 1–195 m) for all patients and 36 months (range, 1–195 m) for living patients. Twelve (2.5 %) patients died within 100 days after ASCT, including 10 patients dying because of toxicity. Twenty-eight (6 %) patients developed a secondary malignancy including acute
myeloid leukemia or myelodysplastic syndrome (n=9), solid tumor (n=9), and missing data (n=10). A trend for a higher incidence of secondary malignancies was found in patients who received a TBI-based conditioning regimen: 8 % (n=17) versus 4 % (n=11) (p=.07). In all, 139 patients died, including 63 cases directly related to MCL itself. Three-year PFS and OS were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively (Fig. 2a). For upfront transplanted patients (n=396, 79 %), 3-year PFS and OS were 66.7 % [95%CI, 61.6–72.3 %] and 82.7 % [95%CI, 78.5–87.1 %], respectively (Fig. 2b). The cumulative incidence of relapse at 1 and 3 years was 13.7 % [95%CI, 10.4–16.9 %] and 36.5 % [95%CI, 31.4–41.3 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136). As shown in Fig. 2, no plateau was observed neither for PFS nor OS. Forty-three patients underwent allogeneic stem cell transplantation at time of relapse, and 24 were reported to be alive with a median FU of 12 months. Prognostic factors In order to avoid bias, analysis of prognostic factors was restricted to patients who underwent ASCT upfront (see Table 2). In univariate analysis, 11 parameters were found to have an impact on both PFS and OS. MIPI, IPI, blastoid variant, percentage of Ki67+ cells, and PS were excluded from the multivariate analysis, as missing data were too important. TBI as independent parameter was excluded from the multivariate analysis, as it was included in the so-called “first line treatment” parameter. In multivariate analysis, three parameters (age at ASCT, status at ASCT, and use of rituximab) showed a statistical predictive value regarding both PFS and OS (Fig. 3). Regarding the nature of treatment upfront, an
Fig. 2 PFS and overall survival for all patients (a) and for patients transplanted upfront (b). PFS progression free survival, OS overall survival
Ann Hematol Table 2 Univariate and multivariate analysis of PFS and OS for patients who underwent AST upfront PFS
OS
Univariate HR 95%CI Sex gender M F Age at diagnosisa
