Comparison of Immune Reconstitution after Unmanipulated HLA-Mismatched/Haploidentical Blood and Marrow Transplantation and Unmanipulated HLA-Matched Sibling Transplantation in Patients with Hematological Malignancies.

Background: Recently, we developed a new method for HLA-mismatched/haploidentical transplantation without in vitro T cell depletion [

Methods: From October, 2005 to May, 2008, we retrospectively analysed data concerning lymphocyte recovery for patients with hematological malignancies (Group A, n=54: AML=20, ALL=13, CML=13, MDS=4, AMML=2, NHL=1, MF=1) who received unmanipulated blood and marrow allografts from HLA-mismatched/haploidentical related donors and those (Group B, n=31: AML=10, ALL=3, CML=17, MF=1) who received allografts from HLA-matched related donors. Patients with HLA-matched donors received myeloablative regimens (a modified Bu/Cy regimen) including a combination of cytosine arabinoside (Ara-C), busulfan, cyclophosphamide, Simustine (MeCCNU). Those with HLA-mismatched/haploidentical donors received the modified Bu/Cy regimen and porcine anti-human thymocyte immunoglobulin. Prophylaxis for GVHD included cyclosporine A (CSA) and short-term methotrexate (MTX) with mycophenolate mofetil (MMF). Immune reconstitution was followed, including CD3⁺, CD4⁺, CD8⁺, CD4⁺ naïve, CD4⁺ memory, CD4⁺CD25⁺ and CD19⁺ cells, monthly. Anti-infectious prophylaxis and follow-up were standard.

Results: Except for HLA-mismatch, and conditioning regimens, median age, gender, disease status at transplant and stem cell source were similar. Premobilization mean lymphocyte and lymphocyte subset numbers in normal donors are considered as control values. CD3⁺ ƒyƒncells approached normal levels between 2 and 4 months primarily due to an increase in CD8⁺ ƒyƒnT cell numbers in both group A and group B, the counts of CD3⁺ cells were significantly higher in group B than group A at 1 month (P<0.0001). During the first 12 months post-transplant, CD4 cell counts were lower in group A as compared with group B (P<0.0001, P=0.019, 0.0003, P<0.0001, and P=0.016 at 1, 2, 3, and 4 months, respectively), whereas there was no difference at 6 and 9 months. The number of CD4⁺CD45RA⁺ cells was very low throughout the study in both groups, being lower in group A than in group B, especially during the first 6 months posttransplant (P<0.0001, P<0.0001, P<0.0001, and P=0.0003 at 1, 2, 3, 4, and 6 months, respectively). Normal levels of CD4⁺CD45RA⁺ cells were not achieved 12 month posttransplant in both groups. Normal levels of CD8⁺ cells were reached by 1 month and 2 month post-transplant in group B and A, respectively. B lymphocytes (CD19⁺) showed low or undetectable counts throughout the first 4 months in both groups, achieving the normal range at 12 months. The concentrations of IgA, IgG, and IgM was lower in group A than group B.

Conclusion: Our results suggest that the immune reconstitution, especially CD4⁺ cells, and CD4⁺CD45RA⁺ cells, during the first 6 months following HLA-mismatched/haploidentical transplantation without in vitro T cell depletion was somewhat delayed compared with those after HLA-matched sibling transplantation.