Impact of Myeloablative Versus Reduced Intensity Conditioning Regimens on Early Lymphocyte Recovery and Its Impact on Transplant Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients with Hematologic Malignancies.
Authors: Kim Dong Hwan (Dennis) , Popradi Gizelle , Kuruvilla John , Gupta Vikas , Minden Mark , Lipton Jeffrey H. , Messner Hans A. 
Published: October 2019

Background: The association between early lymphocyte recovery and improved outcomes after allogeneic (Kim et al BJH 2004) and autologous stem cell transplantation (SCT) has been established. However, the impact of conditioning regimen intensity on early recovery of absolute lymphocyte count (ALC) has not been described. The current study attempted to determine different effect of early lymphocyte recovery on transplant outcomes after allogeneic peripheral blood SCT (PBSCT) followed by myeloablative (MAC) or reduced intensity conditioning (RIC).

Methods: This study retrospectively assessed 225 consecutive allogeneic peripheral blood stem cell recipients at Princess Margaret Hospital, Toronto, Canada between 2000 and 2007. All patients received related donor transplants. Myeloablative conditioning (MAC) was employed in 157 patients (TBI based regimens, n=117; Busulfan based regimens, n=40), while 68 patients received RIC excluding alemtuzumab-containing regimens. The endpoints were overall survival, non-relapse mortality (NRM) and relapse incidence after PBSCT according to the day +30 absolute lymphocyte count (ALC).

Results: No difference in ALC was noted between MAC and RIC groups except at 2 (p=0.036) and 3 months (p=0.036). Eighty patients (36%) had an ALC of 0.5 x 109/L or less at 30 days after SCT. No correlation was noted between the ALC prior to SCT and post-transplant ALC. The 2-year OS was significantly better in patients with an ALC ≥0.5x109/L at 30 days compared to those with an ALC < 0.5x109/L in overall group (75% vs. 48%, p=0.00008; Figure 1A) or in the MAC group (p=0.00005; Figure 1B), but not in RIC group (p=0.3; Figure 1C). The NRM at 1-year was significantly lower in the group with an ALC ≥0.5x109/L at 30 days compared to those with an ALC < 0.5x109/L (14% vs. 32%, p=0.00008), especially in the MAC group (p=0.00002), but not in the RIC group (p=0.5). However, no difference in relapse incidence was noted according to the ALC count either in the overall (p=0.07), MAC (p=0.3), or RIC groups (p=0.4). The incidences of acute or chronic GVHD were not significantly different between MAC and RIC groups. Delayed lymphocyte reconstitution was noted up to 6 months for the group with ALC of 0.5x109/L or less.

Conclusion: Conditioning regimen intensity did not affect day +30 lymphocyte counts. However, we demonstrated that early lymphocyte recovery may be a prognostic marker for improved OS and better NRM after myeloablative allogeneic PBSCT.

Figure 1. comparison of overall survival between groups with high and low ALC counts at day 30 in overall group (A), myeloablative conditioning group (B) and reduced intenmsity conditioning group (C). Figure 1. comparison of overall survival between groups with high and low ALC counts at day 30 in overall group (A), myeloablative conditioning group (B) and reduced intenmsity conditioning group (C).