Rapid B-Cell Recovery Is Predictive of Graft-Versus-Host Disease-Free Survival, Few Infectious Events, and Good Quality-of-Life after Cord Blood Transplantation Using Myeloablative Regimen without Antithymocyte Globulin

Background:

The severity of complications of transplantation is governed mainly by the status of immune reconstitution. Compared to other stem cell sources, cord blood transplantation (CBT) is characterized by an impairment of early T cell immune reconstitution but rapid B-cell neogenesis. In this study, we investigated the kinetics of early B-cell immune reconstitution and its relation with clinical outcome after CBT using myeloablative regimens without antithymocyte globulin (ATG).

Methods:

(1) Between July 2011 and Feb. 2016, 199 patients with malignant hematological diseases who received an unrelated CBT at Anhui provincial hospital were included in this study. The patients received myeloablative conditioning without ATG and cyclosporin A (CSA) and mycophenolate mofetile as graft-versus-host disease (GVHD) prophylaxis in CBT protocols. (2) Dynamic monitoring of blood cells and lymphocyte recovery after CBT. (3)Lymphocyte subsets were assessed by flow-cytometry after fluorochrome-conjugated monoclonal antibodies for T-cells (CD3, CD4, and CD8), B-cells (CD19), and NK-cells (CD56, CD16). Immunoglobulin levels were measured by immunoturbidimetry assay. These analyses were done approximately at 1-6, 9, 12, 18 and 24 months post-transplantation.(4)The relationship between immune reconstitution and clinical outcome was analyzed.

Results: (1) From 1 month after CBT, the absolute monocyte count (AMC) and absolute lymphocyte count (ALC) sustained to increase until month 18, the median ALC, CD3⁺-cell, CD3⁺CD4⁺-cell, and CD3⁺CD8⁺-cell counts achieved normal at month 2, 3, 5, and 2, respectively. The median NK-cell counts achieved normal at month 1 after CBT. (2) Early B-cell recovery was delayed with gradual increase in the number of cells, starting around month 3 after CBT. The median CD19⁺-cell count at days 30, 60 and 90 was 1/µl, 2/µl, and 7/µl, respectively. The median CD19⁺-cell count reached normal at month 5, the counts continue to increase beyond the normal range until month 18 post CBT. The median serum IgM, IgG and IgA levels reached the normal range at month 3, 4, and 9 after CBT, respectively. (3)Thirty-one cases died of severe infection and the median time of death from infection was 91 days after CBT (range, 31-413 days). By assessment of the rate of readmission within 30 days of hospital discharge, the patients with lower counts of CD19⁺ population after CBT has been associated with a higher readmission rates because of infectious episodes and GVHD. Onset of B-cell robust recovery ,which characterized by CD19⁺-cell count greater than 45/µl at month 3, 90/µl at month 4, and 280/µl at month 6, the patients' subsequently readmission-rate was decreased significantly. The 30-day readmission rate was 6.9%,11% and 24% after CBT when the patients achieved robust B-cell recovery at month 3, 4, and 6, respectively.Assessment of B-cell counts within 83 graft samples, 32 of 83 patients had robust B cell recovery at month 3 who received comparable total B-cell and naive B-cell numbers in the grafts. The patients with or without rapid B-cell recovery showing a similar relapse rate (18.56% vs 15.34%, respectively). The 3-year probabilities of overall survival (OS) and disease-free survival (DFS) were 59%, respectively. Conclusion: Patients with rapid B-cell recovery are less likely to develop post-transplant GVHD, infections, and readmitted to hospital. The CD19⁺ B-cell counts may serve as useful predictor of GVHD-free survival, the 30-day readmission rate and quality-of-life after CBT.