Tandem Autologous/Allogeneic Stem Cell Transplantation for Multiple myeloma: Long-Term Outcome of a Retrospective Study
Authors: Fabre Claire , Bennani Jalil , Brebion Alain , Mendiboure Jean , Ribrag Vincent , Ferme Christophe , Auger Nathalie , Menasria Naziha , Bennaceur-Griscelli Annelise , Troalen Frédéric , Lapierre Valérie , Bourhis Jean-Henri 
Published: April 2020

Abstract
Background: Tandem autologous (auto)/allogeneic (allo) stem cell transplantation (SCT) may improve the outcome of patients (pts) with refractory or poor prognosis multiple myeloma (MM).
Patients: From January 1998 to May 2008, 33 pts with MM who underwent tandem auto/allo SCT in our center were retrospectively analyzed. Mean age was 55 years (y) [range 37–72]; M/F was 19/14. At diagnosis pts characteristics were as follows: Salmon-Durie stage III, 26 pts (79 %) and stage II, 6 pts (18 %), respectively (resp.); Ig subtype IgG, 16 pts (49 %), IgA, 9 pts (27 %) and light chains, 7 pts (21 %). Beta-2 microglobulin (B2M) was greater than 3.5 mg/dL in 21 pts (64 %). Cytogenetic data were available in 25 pts. 15 pts (60 %) had a normal karyotype and 10 pts (40 %) a chromosome 13 deletion (del 13). Median time between diagnosis and tandem auto/allo was 32 months (m) [range 7–106]. 32/33 pts received a first-line anthracycline-based chemotherapy. VAD regimen (Vincristine, Adryamycin, Dexamethasone) was induction therapy in 91 % of pts. Auto SCT conditioning was with Melphalan 140 or 200 mg/m2. Pts with del 13 received a tandem auto/allo SCT in first response (30 %), as a planned procedure. However 23 pts (70 %) were chemorefractory and had presented relapse (16 pts) or progression (7 pts) before tandem auto/allo SCT. Among these refractory pts, 8 pts had received 2 lines, 8 pts 3 lines and 7 pts more than 3 lines of treatment, before tandem auto/allo SCT. The disease status at allo SCT included complete response (CR) in 4 pts (12 %), very good partial response (VGPR) in 4 pts (12 %) and partial response (PR) in 12 pts (36 %) resp, according to IMWG. 27 pts (82 %) received SCT from HLA-matched siblings and 6 pts (18 %) from unrelated donors, resp. Allogeneic SCT conditioning was myeloablative in 7 pts (21 %) and associated TBI 12 Gy and Cyclophosphamide 120 mg/kg, whereas it was non myeloablative in 26 pts (79 %) and associated Fludarabine 30 mg/m2/d during 4 days (d), Busulfan 2 mg/kg/d during 2 d and antithymocyte globulin (ATG). GVHD prophylaxis associated Cyclosporine and Methotrexate.
Results: All pts had a sustained donor engraftment. 7/33 pts (21 %) experienced acute GVHD (aGVHD), of whom 2 pts had grade III–IV. 5/33 pts (15 %) developed chronic GVHD (cGVHD), of whom 3 pts had grade III–IV. Cumulative incidence of non relapse mortality (NRM) at 100 d and 1 y, was 24 % and 30 % resp. NRM was related to pneumonia in 88 % of cases. Median follow-up post-tandem auto/allo SCT was 4.3 y [range 0.2–9]. Estimated overall survival (OS) was 54 % [95 % CI 37–70] at 1 y and 31 % [95 % CI 17–50] at 5 y post transplantation. Estimated event-free survival (EFS) was 35 % [95 % CI 21–52] at 1 y and 17 % [95 % CI 8–35] at 5 y post-tandem, with an evidence of a plateau to the curve after 3 y. The overall response rate (OR) was 73 %, with 10 pts (30.5 %), 5 pts (15 %) and 9 pts (27.5 %) achieving CR, VGPR and PR, resp. According to clinical characteristics at diagnosis (age, B2M, del 13), OR was not statistically different. However, when performed in first response, tandem auto/allo SCT was associated with a higher OR (90 % vs 65 %) (p = NS). With current follow-up, EFS was not statistically different for pts receiving tandem auto/allo SCT in first response (p = 0.09).
Conclusion: Our results suggest that tandem auto/allo SCT is feasible in refractory pts and associated with early toxicity. However tandem SCT may improve the outcome of poor prognosis pts.