Low-Dose Serotherapy Improves Early Immune Reconstitution after Cord Blood Transplantation for Primary Immunodeficiencies

Abstract

Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long-term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3(+) engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3(+), CD4(+), and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD.

Reconstitution of adaptive immunity after umbilical cord blood transplantation: impact on infectious complications

“…These factors include the use of high dose of total nucleated cells, use of double UCB units, use of UCB from related donor and of HLA well-matched UCB unit, and a positive recipient CMV serology before transplantation (62). Conversely, similarly to what is reported after transplantation with conventional graft source, T-cell depleting approaches (such as with ATG or with alemtuzumab) and occurrence of GVHD significantly hamper T-cell recovery after UCBT (31,(62)(63)(64)(65). Concerning the impact of ATG, it was recently demonstrated in a large cohort of pediatric patients, that even very minimal exposure to ATG in the setting of UCBT has a significant detrimental effect on early CD4 + T-cell recovery (63).…”

“…The use of ex vivo T-cell depleted graft (30) or in vivo T-cell depleting approaches (i.e., with alemtuzumab, an anti-CD52 monoclonal antibody; or with anti-T cell globulin, ATG) was reported to compromise peripheral T-cell expansion (31)(32)(33)(34)(35)(36). Impaired thymopoiesis after ATG-conditioned alloHSCT was also described in some (37) but not all (35) studies, although this may vary depending on the brand of ATG.…”

“…However, although some groups observed impaired quantitative B-cell recovery after alloHSCT with ATG (71), others reported higher numbers of circulating B cells in ATG-conditioned patients (35,36). Few studies have assessed the effects of alemtuzumab exposure on circulating B-cell counts after alloHSCT and reported no significant impact (31)(32)(33).…”

Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT

“…14,[16][17][18] The pharmacokinetics of alemtuzumab are complicated, and there is tremendous interpatient variability. 18,19 Alemtuzumab is a humanized monoclonal antibody targeted against CD52, which is expressed by most lymphocytes.…”

A glance on recent progresses in diagnosis and treatment of primary immunodeficiencies/ Progrese recente în diagnosticul şi tratamentul imunodeficienţelor primare

“…Very early transplantation (indicated by family history or population-based NBS) significantly improves out-come irrespective of donor choice, conditioning regimen used, and underlying genetic diagnosis. Other factors of steadily and incrementally improving HSCT outcome encompass reduced intensity condition regiment, increasing expertise in ablation of certain donor cell populations in order to provide a balance between engraftment and graft-versus-host disease (GvHD), low dose serotherapy new drugs allowing reduction of veno-occlusive disease, close viral and fungal surveillance, and more sophisticated supportive care (85)(86)(87). Very recent US NBS data indicate that a prolonged time window for transplantation might be gained when timely TREC-NBS prompt immediate measures to avoid infections and organ damage.…”