Context Of Hematopoietic Stem Cell Transplantation Research Articles

Persistent hypersplenism following successful hematopoietic stem cell transplantation: unraveling the cellular components of extramedullary residual disease and donor hematopoiesis—a case report

In this study, we report an unprecedented case of graft failure following hematopoietic stem cell transplantation (HSCT) in a patient with a myeloproliferative neoplasm (MPN) who had achieved bone marrow (BM) remission. We outline the intricate cellular components of splenic hematopoiesis, which are derived from both the recipient and the donor, underpinning the persistence of fibrosis. Our investigation characterizes the distinct cellular populations that play a pivotal role in graft exhaustion and introduces an unusual hypothesis regarding the perpetuation of a malignant niche in extramedullary sites within the context of HSCT.

Study protocol for a phase II, multicentre, prospective, non-randomised clinical trial to assess the safety and efficacy of infusing allogeneic activated and expanded natural killer cells as consolidation therapy for paediatric acute myeloblastic leukaemia

IntroductionAcute myeloblastic leukaemia (AML) constitutes the second most common haematological malignancy in the paediatric population. Current treatment regimens are based on the administration of polychemotherapy, combining high doses of cytarabine...

Understanding the Relationship Between Child Health-Related Quality of Life and Parent Emotional Functioning in Pediatric Hematopoietic Stem Cell Transplant.

Explore interrelationships between domains of child health-related quality of life (HRQL) and parent emotional functioning using parent-proxy and child report in the context of hematopoietic stem cell transplant (HSCT). Data on 258 parent-child dyads were used from two longitudinal studies. Domains of HRQL included physical, emotional, and role functioning, and HSCT-related worry. We used structural equation modeling to model the outcome of parent emotional functioning using primary and alternative conceptual models. Parent-proxy raters reported lower child HRQL than child raters. Structural equation models demonstrated relationships between child emotional functioning, child HSCT-related worry, and parent emotional functioning, with some differences by raters. Relationships between child HRQL and parent emotional functioning within the context of HSCT are complex. To optimize the child's health outcomes, providing psychosocial support for children and their families may be necessary, especially for those experiencing distress or facing treatment complications.

Intravenous Busulfan

An intravenous formulation of busulfan, a cytotoxic bifunctional alkylating agent, has been developed to replace oral busulfan as a conditioning treatment prior to hematopoietic stem cell transplantation (HSCT) in pediatric patients. Doses of intravenous busulfan based on actual bodyweight, but not age, reduce inter- and intraindividual variability in exposure. In a study of intravenous busulfan as a conditioning treatment prior to allogeneic or autologous HSCT, the majority of pediatric patients, who received one of five bodyweight-based doses, achieved busulfan area under the plasma concentration-time curve (AUC) values within the targeted therapeutic range. Although mean busulfan clearance values were highly variable between bodyweight strata, exposure was not affected, with no significant differences between bodyweight groups in mean AUC values. The achievement of therapeutic AUC values with intravenous busulfan resulted in a high rate of sustained engraftment, low transplant-related mortality, and promising survival outcomes post-transplant. Intravenous busulfan was considered to be well tolerated, in the particular context of HSCT, and no failure of HSCT due to organ toxicity was reported. Nonhematologic adverse events commonly associated with busulfan conditioning regimens were frequent, but generally of mild to moderate severity. The intravenous busulfan regimen was frequently associated with elevated liver enzymes, but hepatic veno-occlusive disease (HVOD) was infrequent, of mild to moderate severity, and resolved within 10 days of diagnosis. Unlike oral busulfan, intravenous busulfan does not appear to be associated with severe HVOD or death due to organ toxicity.

Anti-tumor activity of partially HLA-matched irradiated blood mononuclear cells in patients with advanced malignancies

2552 Background: We previously demonstrated the safety and efficacy of HLA-haploidentical blood mononuclear cells (MNCs) administered in the absence of preparative therapy to patients with metastatic renal cell carcinoma (RCC) (J Clin Oncol 21:3785–91.2003). The efficacy of this therapy is evaluated further in patients with advanced malignancies. Methods: Patients with advanced malignancies who had HLA- haploidentical donors were enrolled. Donors underwent 12–15 L leukapheresis. MNCs were processed by irradiation (25 Gy) and immediately infused. Disease evaluation was undertaken every 8 weeks. Repeat infusions were given every 8 weeks until disease progression. Results: 30 patients with diverse diagnoses, including 9 patients with a hematological malignancy were treated. Three of 13 patients with RCC had disease response, and 1 of 2 patients with melanoma had a mixed response. A patient with imatinib mesylate-refractory chronic myelogenous leukemia (CML) had a transient response. A patient with refractory acute myelogenous leukemia (AML) had disease response in conjunction with therapy. Treatment was associated with minimal toxicity and radiographic responses in patients with RCC did not occur until after 2–3 treatments. Host CD8+ cells reactive with the Pr-1 peptide of proteinase 3 were induced in association with disease response in a patient with AML. Additional studies identifying disease targets and mechanisms by which infusion of irradiated HLA-haploidentical cells are associated with disease response are ongoing. Conclusions: Disease response is seen with irradiated allogeneic MNCs administered outside the context of hematopoietic stem-cell transplantation. Evidence for anti-tumor activity is seen in isolated patients with RCC, melanoma, CML and AML. The temporal nature of the response in RCC in combination with the very limited survival of the infused cells raises the possibility of induction of a host-mediated anti-tumor effect. This hypothesis is supported by induction of host CD8+ T cells reactive with a tumor-associated peptide in a patient with AML. Given the lack of toxicity, broad availability of related haploidentical donors and the relative low financial cost, this form of cellular therapy should be developed further. No significant financial relationships to disclose.