Abstract
Autologous hematopoietic stem cell transplantation (ASCT) after melphalan (Mel) conditioning has been shown to improve outcomes in patients (pts) with multiple myeloma (MM), including complete response (CR), disease free and overall survival (OS). Successful collection and subsequent stem cell rescue with adequate number of CD34+ stem cells are key to achieving these goals, including reduced platelet (plt) engraftment times and lower cumulative incidence of relapse (CIR). However, there has been some discordance regarding the optimal CD34+ dose and the effect of the cell dose on the time to plt engraftment, dependency on plt transfusion in the post-ASCT period, and subsequent CIR.
A retrospective analysis of 275 consecutive MM patients who underwent ASCT between 2010-2017 at a single institution was performed to determine the relationship between CD34+ stem cell infusion dose and plt recovery, dependence on plt transfusion in the post-ASCT period as well CIR. Platelet recovery was defined by the first of the 3 consecutive days with plt count ≥ 20 x 109/L while remaining transfusion free for 7 preceding days. Analyses were done separately by age groups (< 65 years and ≥ 65 years) and by Mel conditioning received (140 mg/m2 vs. 200 mg/m2). The Mann-Whitney test was used to compare the median plt engraftment times and dependence on plt transfusions between the groups with < 2.5 vs. ≥ 2.5 x 106 (mill) CD34+ cells/Kg infused; Fisher's exact test was used to assess the effect on achieving plt recovery; Gray's test was used to compare CIR curves; log-rank test was used for comparisons of OS curves. CIR was defined as the probability of having had a relapse after achieving a response with death without experiencing a relapse as a competing event.
Overall, there were 79 pts age ≥ 65 (median 68, range 65-75) and 196 pts age < 65 (median 58, range 34-65). Median time in days (d) to engraftment of plts was shorter for pts who received ≥ 2.5 mill (median 3.3, range 2.5-19.9) vs. < 2.5 mill cells/Kg (median 2.2, range 0.8-2.4): 24 vs. 25 d in both age groups < 65 and ≥ 65 years (p=0.0005 and 0.036, respectively). Patients who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg also required at least 1 plt transfusion vs. none, in both age groups (p=0.048 and 0.022, respectively). CIR was statistically different among the 4 groups analyzed (age<65/CD34+<2.5 vs. age<65/CD34+≥2.5 vs. age≥65/<2.5CD34+ vs. age≥65/CD34+≥2.5, p=0.015): the lowest 3 year CIR of 26% was seen in age<65/CD34+≥2.5 group, and the highest 52% in age≥65/<2.5CD34+ group. Median hospital stay, OS or disease response [CR vs. partial response (PR)] at day +100 were not statistically different amongst the two groups, regardless of the CD34+ stem cell dose infused, or the age group analyzed.
Overall, there were 74 and 201 pts who received 140 mg/m2 vs. 200 mg/m2 of Mel conditioning, respectively. While there was no statistical difference in plt transfusion requirement in Mel140 mg/m2 pts with respect to the CD34+ cell dose (p=0.069), Mel 200 mg/m2 pts who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg required longer plt engraftment time (25 vs. 24 d, respectively, p=0.001). Patients who received < 2.5 vs. ≥ 2.5 mill CD34+ cells/Kg also required at least 1 platelet transfusion vs. none, in both Mel 140 mg/m2 vs. Mel 200 mg/m2 groups (p=0.047 and 0.001, respectively). CIR was statistically different among the 4 groups analyzed (Mel140/CD34+<2.5 vs. Mel140/CD34+≥2.5 vs. Mel200/<2.5CD34+ vs. Mel200/CD34+≥2.5, p=0.005, Figure 1.): the lowest 3 year CIR of 4% was seen in Mel140/CD34+≥2.5 group, and the highest 27% in Mel200/CD34+<2.5 group. Median hospital stay, OS or disease response (CR vs. PR) at day +100 were not statistically different among the two groups, regardless of the CD34+ stem cell dose infused, or the Mel conditioning received.
Our single institution experience suggests that infusion of ≥ 2.5 mill CD34+ cells/Kg in both age groups, or with Mel200 mg/m2 conditioned patients is a more optimal CD34+cell dose for ASCT in MM that shortens platelet reconstitution, and reduces the need for plt transfusions in the post-ASCT period. The same CD34+ cell dose also argues for the lower rates of CIR, where it appears to abrogate the effects of lower Mel conditioning. These curious findings which imply yet unelucidated stem cell graft influence require further analysis and replication in larger cohorts, while for now they may serve to instruct stem cell collection practices for ASCT in MM.
Baljevic: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Holstein: Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees. Lunning: Celgene: Consultancy; BMS: Consultancy; Genentech: Consultancy; Spectrum: Consultancy; Onyx: Consultancy; TG Therapeutics: Consultancy; Gilead: Consultancy; Juno: Consultancy; Epizyme: Consultancy; AbbVie: Consultancy; Pharmacyclics: Consultancy.
