Impact of Pre-Transplantation, Mobilization and Graft Variables on Transplant Outcome after Autologus Hematopoietic Stem Cell Transplantation in Multiple Myeloma in Patients
Authors: Michallet Mauricette , Le Quoc Hung , Sobh Mohamad , Raus Nicole , Clarck Melissa , Vial Jean , Clapisson Gilles , Paillet Carole , Nicolini Franck E , Troncy Jacques , Thomas Xavier , Chelghoum Youcef , Nicolas-Vierlizier Emmanuelle , Cannas Giovanna , Plesa Claudiu , Baracco Fiorenza 
Published: April 2020

Abstract
This analysis studied 197 autologous HSCT performed in 132 patients treated for multiple myeloma (MM) in our center between 2000 and 2007. There were 53 females and 79 males with a median age of 56.8 years (34–72). At diagnosis there were 71 IgG (49κ, 22λ), 26 IgA (15κ,11λ), 2 IgD (1κ, 1λ), 27 light chain (18κ,9λ), 2 plasma cell leukemia, 3 non secretory, 1 non secretory/non excretory. There were 11 stage I (10A and 1B), 12 IIA, 96 III(75A and 21B) and 13 not classified. At diagnosis, 24/98pts had a del(13), and 65/179 had high levels of β2microglobulin. Before 2004, 50% of transplants were done and the median interval between diagnosis and HSCT was 7.8 months (3.5–131). We divided the population into 2 groups (I = 65: double-auto, II = 67 simple auto). The disease status pre-transplant according to the number of apheresis were: 1 apheresis (group I: 3CR, 29PR, 3SD, 1PD; group II: 2CR, 24PR, 3PD), 2 apheresis (group I: 16PR, 1SD, 1PD; group II: 3CR, 9PR, 1PD), 3 apheresis (group I: 1CR, 4PR; group II: 10PR, 1unknown), 4 apheresis (group I: 4PR, 1PD; group II: 1CR, 10PR, 2SD), 6 apheresis (group II: 1PR) and 8 apheresis (group: 1PR). PBSC were mobilized in steady state in 135 cases, 53 after cyclophosphamide alone, 9 cyclophosphamide with other drugs. During mobilization, we used GCSF in 179cases, GM-CSF in 5cases, SCF in 4 cases and associations of GM-CSF+ GCSF in 2(1%) cases and SCF+GCSF in 7(3.5%) cases. The median number of infused cells were: TNC 5×107/kg (1–59), CFU-GM 70.5×104/kg (0–2616) and CD34+cells 3×106/kg (0–27). Of these, 115 (58%) had a number of CD34+cells&lt;4×106/kg and 82 (42%) ≥4×106/kg. As conditioning regimens, all pts received melphalan alone with a median total dose of 304mg [130–440]. After transplantation, 156(79%) have received growth factors [1(0.5%) GM-CSF, 148 (95%) G-CSF and 7 (4.5%) SCF] and 195 pts well engrafted (99%). Concerning red blood cell (RBC) transfusions, 60% of pts did not received any RBC transfusions, 30% received between 1 and 4 transfusions, 7% between 5 and 8 and 3% 10 or more and concerning platelet (Pt) transfusions, 35,5% did not received any Pt transfusions, 53% received between 1 and 3, 9% between 4 and 7 and 2.5% 10 or more. The median number of RBC and Pt transfusions were 0 [0–23] and 1 [0–20] respectively. The median number of days with neutrophils &lt;0.5G/L was 6 (0–33) and with Pt&lt;50G/L 17 (2–104) and the median length of hospitalization for auto transplantation was 18 days (14–54). The probability of 5-year overall and event-free survival (OS and EFS) were 64.3% (56.3–73.4%) and 32.4% (24.9–42.2%) and the median OS was not reached. Among all pts, 25 received an allogeneic HSCT as further treatment. Statistical analysis studied age disease status at transplant infused TNC, CD34+cell and CFU-GM, growth factors during mobilization and after transplantation, mobilization chemotherapy, interval Diag-T and transplantation period in
a conditional logistic-regression model to analyze associations between these variables and length of hospitalization, number of RBC and Pt transfusions; a multivariate analysis using Cox model to analyze the impact of these variables on length of aplasia (&lt;0.5G/L neutrophils and &lt;50G/L Pt).
We observed no significant impact of all studied variables on length of hospitalization and RBC transfusions and a significant negative impact of long interval diagnosis-T (p=0.05) and of the period &gt; 2004 on Pt transfusion number (p=0.03). We showed a significant positive impact of CFU-GM number [HR=1 (1000–1.002) (p=0.03)] and growth factor use after transplantation [HR=0.55 (0.36–0.85) (p=0.005)] on days &lt;0.5 G/L neutrophils and a significant negative impact of CD34+cell&lt;4 ×106/kg on the number of days &lt;50G/L Pt ([HR=1.65 (1.09–2.50) (p=0.01)]. A more refined analysis of the groups, as well as a medico-economic analysis are ongoing and will be presented. In conclusion, this retrospective analysis showed an interesting long-term overall survival probability for this high risk MM population. We demonstrated no apparent impact of the pre-transplant, mobilization, and graft variables on number of transfusions and the length of hospitalization in this global analysis. However, we did show a significant influence of the diagnosis-T interval on platelet transfusions and of the CD34+ cell number, GCSF post-transplant and CFU-GM number on the length of aplasia.