Lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant predicts non-relapse mortality in patients with acute leukemia or myelodysplastic syndrome

Abstract

To clarify the clinical significance of lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant (allo-HSCT), we retrospectively studied 157 patients with hematologic malignancies who underwent allo-HSCT. An absolute lymphocyte count < 500/μL was defined as lymphocytopenia. There was a significant relationship between lymphocytopenia and advanced disease at allo-HSCT or corticosteroid administration within 100 days. Lymphocytopenia on day 100 (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.3-4.5; p = 0.006) and advanced disease at allo-HSCT (HR: 2.2; 95% CI: 1.3-3.9; p = 0.005) were prognostic factors for overall survival by multivariate analysis. Advanced disease was significantly associated with relapse (HR: 2.8; 95% CI: 1.5-5.4; p = 0.002), while lymphocytopenia was an independent predictor of non-relapse mortality (HR: 2.8; 95% CI: 1.1-6.8; p = 0.027). These results suggest that lymphocyte recovery on day 100 may be an important predictor of late complications in patients receiving allo-HSCT for hematologic malignancies.

Optimal Threshold and Time of Absolute Lymphocyte Count Assessment for Outcome Prediction after Bone Marrow Transplantation

“…Whereas we studied ALC on various days from þ30 to þ180, most of the previous studies used ALC on days 21 to 30 [14,15,17,18,[20][21][22][24][25][26], indirectly assessing NK cell recovery, because NK cells are the dominant lymphocyte subset for 3 to 4 weeks post-SCT [30,31]. Among the few studies assessing the impact of ALC after day 30 [13,16,19], only Kim et al [13] used a methodology (restricted cubic spline smoothing) to assess different ALC cutoff levels; however, instead of individually calculating HRs for each different ALC cutoff level, they performed a single analysis in which day 30 ALC values were stratified into 5 comparison arms (0-200, 200-300, 300-400, 400-500, and >2600) and 1 reference arm (500-2600). An ALC of 200 was chosen to assess outcomes, because it was significantly higher than the reference group.…”

“…41% versus 18% (P < .001) Yamamoto et al, 2014 [16] 206 patients with AML/ ALL/MDS; MA and RIC; all sources and donors Rationale not provided At 3 yr: At 3 yr: Grade III-IV: Extensive: 300 at day 21 14% versus 27% (P ¼ NS) 25% versus 20% (P ¼ NS) 16% versus 12% (P ¼ NS) 18% versus 13% (P ¼ NS) 300 at day 30 21% versus 13% (P ¼ NS) 21% versus 26% (P ¼ NS) 18% versus 16% (P ¼ NS) 21% versus 11% (P ¼ NS) Ishaqi Note. Where percentages are given for OS, RFS, NRM, RI, and GVHD incidence, the first and second percentages indicate the survival/incidence in the low-ALC and high-ALC groups, respectively.…”

“…ALC after SCT may be a surrogate marker for immune reconstitution and a predictor of these complications. Various studies have shown that a delayed recovery of lymphocytes after SCT increases nonrelapse mortality (NRM) and relapse incidence (RI), shortening survival [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]; however, most of those studies included cohorts with few patients, proposed a wide range of arbitrary time points and thresholds with conflicting findings on relapse and survival, and incorporated SCTs from different graft sources (Table 1).…”

Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate mofetil prophylaxis in the Japanese population

“…Immune reconstitution affects clinical outcomes after allogeneic hematopoietic stem cell transplantation (HSCT), as the donor lymphocytes help reconstitute the host's immune system, prevent infectious complications, and prevent disease relapse through a graft-versustumor effect. Thus, rapid lymphocyte recovery is generally associated with a survival benefit after HSCT [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. However, previous studies incorporated HSCTs from different graft sources and covered a broad range of arbitrary post-transplant assessment time points and thresholds, which generated conflicting findings regarding relapse and survival.…”

“…However, previous studies incorporated HSCTs from different graft sources and covered a broad range of arbitrary post-transplant assessment time points and thresholds, which generated conflicting findings regarding relapse and survival. Furthermore, few studies have examined lymphocyte recovery in Asian cases with mycophenolate mofetil (MMF) prophylaxis for graft-versus-host disease (GVHD) [3,5,14]. Those analyses are important, as racial and ethnic diversity can affect clinical outcomes after HSCT.…”