Cellular Immune Reconstitution and Its Impact on Clinical Outcome in Children with β Thalassemia Major Undergoing a Matched Related Myeloablative Allogeneic Bone Marrow Transplant

Abstract

We have prospectively analyzed cellular immune reconstitution (IR) in 63 consecutive pediatric patients with beta thalassemia major who underwent an HLA matched related allogeneic bone marrow transplant (BMT). Samples from bone marrow graft and posttransplant peripheral blood samples from recipients at specified time points were assessed for IR of cellular subsets. The median age of the cohort was 7 years, and there were 37 (59%) males. A CD34 cell dose above the median value of 7.3 x 10(6)/kg had a lower incidence of bacterial (P = .003) and fungal (P = .003) infections in the posttransplant period, and was not associated with an increased risk of graft-versus-host disease (GVHD). Among cases that did develop grade II-IV GVHD the absolute CD8 (116 versus 52 cells/microL, P = .012), CD8 naïve (74 versus 9 cells/microL, P = .005), and CD8 memory counts (44 versus 21 cells/microL, P = .010) were significantly higher on day 15. Fifteen patients (24%) rejected their graft (7 primary and 8 secondary). The day 28 natural killer (NK) cell count was significantly associated with secondary graft rejection, event-free survival (EFS), and overall survival (OS) (P = .044, .013, and .034, respectively). On a multivariate analysis, patients with a day 28 NK cell count below the median value of 142/microL had a significantly higher rejection rate (hazard ratio [HR] = 11.1, P = .038) and a lower EFS (HR = 16.3, P = .034).

Infectious complications following allogeneic stem cell transplantation by using anti‐thymocyte globulin‐based myeloablative conditioning regimens in children with hemoglobinopathies

“…Few studies have evaluated the incidence and characteristics of infectious complications in patients with hemoglobinopathies after allo‐HSCT . Specifically, in the setting of myeloablative ATG‐containing regimens, the epidemiology of transplant‐related infections is even more poorly defined.…”

Psychosocial factors and hematopoietic stem cell transplantation: Potential biobehavioral pathways

“…Neutrophil recovery above neutropenic levels (defined as neutrophil count <500/mm 3 ), when the patient is most susceptible to bacterial infections, and platelet recovery above which transfusion is indicated, typically occur an average of two weeks post-transplant (Hogge et al, 2000), though this varies depending on stem cell source and dose, age, and transplant type. Natural killer (NK) cells and dendritic subsets typically recover to normal levels within 1–2 months (Rajasekar et al, 2009). While innate immunity recovers within several weeks, B cell and CD8 + T cell numbers take several months to normalize, with CD4 + T cells taking years to recover, or, in the presence of chronic GVHD, perhaps never recover.…”

“…Further, day 30 NK cell counts were positively associated with rapid molecular remission in patients with myeloid malignancies. Conversely, decreased numbers of NK cells at day 28 post-transplant were associated with secondary graft rejection (Rajasekar et al, 2009) and relapse in allogeneic transplant recipients (Klyuchnikov et al, 2010). In sum, NK cells are important for transplant success and their administration has proven to be a beneficial adaptive immunotherapy (Passweg et al, 2004), preventing relapse in some HCT recipients (Miller et al, 1994).…”

Improved Clinical Outcomes of High Risk β Thalassemia Major Patients Undergoing a HLA Matched Related Allogeneic Stem Cell Transplant with a Treosulfan Based Conditioning Regimen and Peripheral Blood Stem Cell Grafts

“…It is especially attractive in the context of an allogeneic SCT for high risk β thalassemia major because of its reported low hepatic toxicity profile and consistent pharmacokinetic profile which are both significant problems with conventional busulfan in this population [5], [13], [14]. Bone marrow has been the preferred choice of stem cells to reduce the risk of graft versus host disease (GVHD) in this non malignant condition, though the incidence of both acute and chronic GVHD in this predominantly pediatric population is low [14], [15]. Recently a similar low incidence of acute and chronic GVHD with a PBSC graft in the setting of matched unrelated transplants has been reported from China [16].…”