Reconstitution of Lymphocyte Subsets and Outcomes After Matched and Mismatched Hematopoietic Stem-Cell Transplantation

Allogeneic stem-cell transplantation (ASCT) is curative for many malignant and nonmalignant hematological disorders. We aimed to study reconstitution of lymphocyte subsets after matched and mismatched transplantation.

Lymphocyte subsets  were evaluated by flow cytometry at 1,3,6 and 12 months (mo) post-ASCT. Lymphocyte recovery was determined using means at each time point and group differences assessed using analysis of variance.Time-to-event outcome were estimated by Kaplan-Meier survival curves and the log-rank test was used to evaluate differences between groups. 100 patients (pts) were included in the study: 25 received a matched sibling (MSD), 20 pts a matched unrelated donor ASCT 10/10 (MUD), 18 pts a 9/10 MUD, 9 pts a T cell depleted haploidentical (TCD haplo), and 28 a T cell replete haploidentical transplant (TCR haplo). 53 pts received bone marrow and 47 peripheral blood stem cells. Most patients were treated for acute leukemia (AML 41, ALL 23), 16 MDS, 6 CML, 4 CLL, 5 lymphoma. Median age was 43 years (range: 20-71). Median follow-up was 13.6 mo. 60 pts were alive and disease-free at last follow-up and 28 pts died 75% of relapse. Non-relapse mortality (NRM) was 6% for the entire cohort.       

Overall, alive pts (vs. who died) had higher mean CD3 (615 vs. 349, p=0.03 on day 90), CD8 (427 vs. 187, p=0.03 on day 90), CD4 (391 vs. 54, p=0.01, on day 365), and lower mean CD56 cells (178 vs 300, p=0.01, on day 30) post ASCT. Pts who progressed (vs. did not), had lower 1 year mean CD4 (123 vs. 394, p=0.02), lower mean CD3 (359 vs. 1147, p=0.06), with no differences in CD8, NK, and CD45RA cells. NRM was associated with higher mean NK counts at 6 months (499 vs. 188, p=0.01) and with lower mean CD3 at day 90 (184 vs. 557, p=0.07). T-cell recovery occurred most rapidly in MSD transplants (Figure1), and interestingly, higher CD4CD25 cell numbers recovered early and most rapidly in the MSD transplants, which may partly explain a lower incidence of GVHD in this group. Overall, TCR haplos had a similar pattern of T-cell recovery and outcomes as 10/10 MUDs (Figure1). No significant differences in T cell subsets found between these two groups for CD3, CD4, CD8, CD45RA and CD4CD25 at any time-point. TCD haplos had most impaired T-cell reconstitution and outcomes (Fig. 1), characterized by early NK cell and delayed CD3, CD4, CD8 recovery. Interestingly, pts surviving 6-9 months post-transplant recovered CD3, C4, CD8 cells; however, naïve T-cell recovery was impaired for more than >1 year post-transplant, suggesting that T cell recovery comes predominantly from the memory T cell compartment.

In conclusion, recovery of lymphocyte subsets may vary widely with the type of transplant, may correlate with outcomes, and should be further explored post-transplant.