Autologous Stem Cell Transplantation (ASCT) for Patients Aged 60 Years or Older with Classical Hodgkin Lymphoma : A Retrospective Analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)
Authors: Stamatoullas Aspasia , Brice Pauline , Gueye Mor Seny , Chevallier Patrice , Bouabdallah Reda , Nguyenquoc Stephanie , Francois Sylvie , Turlure Pascal , Ceballos Patrice , Monjanel Helene , Bourhis Jean-Henri , Guillerm Gaelle , Mohty Mohamad , Biron Pierre , Cornillon Jérôme , Cordonnier Catherine , Bonmati Caroline , Tabrizi Reza , Huynh Anne , Bernard Marc , Caillot Denis , Peffault de Latour Régis , Tilly Hervé 
Published: October 2019

Abstract
Background: Twenty percent of classical Hodgkin Lymphoma (cHL) patients are aged 60 years or older. Their survival rate is inferior to that of younger patients for several reasons including lower delivery of standard chemotherapy and toxicity excess. For relapsed or refractory (R/R) cHL young patients, autologous stem cell transplantation (ASCT) is a standard of care after salvage chemotherapy. However, little is known regarding the outcome of R/R cHL in elderly patients (≥60 years) receiving ASCT.
Method: The current report retrospectively analyzed the outcome of all consecutive patients aged 60 years or older with the diagnosis of R/R cHL who were transplanted between 1992 and 2013 and who were reported to the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) registry. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centers. This study was approved by the scientific committee of the SFGM-TC and is in accordance with Helsinki declaration for clinical research. Of note, specific study questionnaires were sent to transplant centers to obtain comprehensive, updated data.
Results: One hundred and twenty patients met these criteria. Ninety-one patients (63M/28F) with documented data from 28 transplant centers were analyzed. Median age was 63 years at transplant (range 60-75). At diagnosis, 64 patients had advanced stage cHL, 46 had B symptoms and 6 had poor performance status (ECOG 2). Thirty-four patients had primary refractory disease, and 22 patients relapsed within the first year after first CR. The median number of salvage chemotherapy regimens was 2 (range 1-4). Most of the patients showed disease sensitivity to salvage treatment with 52 patients transplanted in CR, 5 patients in CRu, 30 patients in PR and 1 patient transplanted with progressive disease. The most frequently used conditioning regimen consisted of BEAM chemotherapy (93%) (Carmustine 300 mg/m2 d-6, Etoposide 100 mg/m2 Q12H d -5 to -2, Cytarabine 200 mg/m2 IV Q12H d-5 to -2, Melphalan 140 mg/m2 d -1). The median number of CD34 peripheral blood stem cells was 4.2 106 cells/kg (range 0.9-17.8). The median duration of hospitalization was 22 days (8-49). The median time to achieve neutrophil count &gt;1x109/L and platelet count &gt; 20x109/L were 11 days (range 8-104) and 13 days (range 7-115), respectively. Grade 3-4 toxicities occurred in 24 patients (mucositis: 13, sepsis: 3, interstitial pneumonia: 2, diarrhea: 2, heart failure: 2, multiorgan failure (MOF): 1, unspecified case: 1. With a median follow-up of 32 months (range 1-185), the 6-year estimate of OS was 64% (95% CI 51-75). In univariate analysis, none of the usual prognostic factors (gender, age ≥ 65, disease status before transplant, CD34+ cells count, time to relapse &lt; 1 year, disease stage at relapse, Hb level) significantly influenced OS. At last follow-up, 13 patients died: 5 from toxicity (1 MOF, 2 interstitial pneumonia, 1 heart failure and 1 invasive pulmonary aspergillosis), 4 from disease progression, and 4 from unspecified causes.
Conclusion: This retrospective study with long term follow-up, despite its limitations, suggests that in selected elderly patients ASCT is a valid treatment option for chemosensitive R/R cHL patients, with an acceptable rate of toxicity warranting further investigations in the era of novel agents such as brentuximab.

Disclosures
Brice: Seattle Genetics, Inc.: Research Funding; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Roche: Honoraria.