Autograft-Absolute Lymphocyte Count Infusion Predicts Survival in Double/Triple Hit Lymphomas Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation
Authors: Porrata Luis F. , Inwards David J. , Ansell Stephen M. , Micallef Ivana N. , Johnston Patrick B. , Villasboas Jose , Paludo Jonas , Markovic Svetomir N. 
Published: November 2021

Abstract
The autograft absolute lymphocyte count (A-ALC) ≥ 0.5 x 10 9 cells/kg is a survival prognostic factor for lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). However, the A-ALC ≥ 0.5 x 10 9 cells/kg has not been tested as prognostic factor against double hit/triple hit lymphomas (DHL/THL). Thus, we set up to investigate if A-ALC ≥ 0.5 x 10 9 cells/kg is a prognostic factor for overall survival (OS) and progression-free survival (PFS) for DHL/THL post-APBHSCT. From January 2012 until December 2020, we identified 77 DHL/THL patients treated with APBHSCT. All patients required to have the diagnosis of DHL/THL by FISH for rearrangements of MYC, BCL2, and BCL6. Of the 77 patients, 62 patients were classified as DHL and 15 patients as THL. Of the DHL, 82 % (52/68) had the MYC/BCL2 and 16% (10/62) the MYC/BCL6 rearrangements. Dividing the cohort into two groups (A-ALC ≥ 0.5 x 10 9 cells/kg and A-ALC &lt; 0.5 x 10 9 cells/kg), both groups were balanced in regard to de novo versus transformed histology (p = 0.3), cell of origin (p = 0.6), DHL and THL (p = 0.6), MYC/BCL2; MYC/BCL6; and MYC/BCL2/BCL6 rearrangements (p = 0.6), first line chemotherapy (p = 0.2), salvage chemotherapy (p = 0.5), disease status prior to APBHSCT (CR1, CR, and PR) (p = 0.07), stem cell mobilization (Plerixafor versus not) (p = 0.6), and infusion of CD34 count (p = 0.2). With a median follow-up of 20.4 months (range, 0.4-94.5 months) for the entire cohort and with a median follow-up of 33.5 months (range, 3.5-94.5 months) for the patients that remained alive, DHL/THL patients infused with A-ALC ≥ 0.5 x 10 9 cells/kg experienced superior OS (HR = 0.251, 95%CI 0.117-0.539, P &lt; 0.0004) and PFS (HR = 0.347, 95%CI 0.160-0.753, P &lt; 0.007). The 5-year OS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% confidence interval [CI], 52%-87%) and for the A-ALC &lt; 0.5 x10 9 cells/kg group was 18% (95% CI, 7%-39%) (Figure 1A). The 5-year PFS rates for the A-ALC ≥ 0.5 x10 9 cells/kg group was 73% (95% CI, 59%-85%) and for the A-ALC &lt; 0.5 x10 9 cells/kg group was 13% (95% CI, 5%-33%) (Figure 1B). Multivariate analysis showed that A-ALC was an independent predictor for OS (HR =0.178, 95%CI 0.052-0.614, p &lt;0.005) and PFS (HR = 0.400, 95%CI 0.189-0.850, p &lt;0.02). Our study showed that A-ALC is a prognostic factor for survival in DHL/THL patients undergoing APBHSCT. Our current practice for all lymphoma patients is not only to collect enough stem cell for hematologic engraftment, but also A-ALC ≥ 0.5 x 10 9 cells/kg to improve clinical outcomes post-APBHSCT.
Figure 1 Figure 1.

Disclosures
Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Paludo: Karyopharm: Research Funding.