Measuring Patient Preferences to Inform Clinical Trial Design: An Example in Rheumatoid Arthritis.

Background: Allogeneic bone marrow transplantation (BMT) may be a curative treatment for patients with rheumatoid arthritis (RA), but it has serious risks, including death. It is uncertain whether patients would accept the risks and benefits of BMT and participate in clinical trials. We conducted a discrete choice experiment (DCE) to quantify risk tolerance and benefit-risk trade-offs to inform the design of a clinical trial for BMT.

Chronic liver disease after allogeneic hematopoietic cell transplantation.

Background Aims: There are few descriptions of the epidemiology of chronic liver disease (CLD) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Among those transplanted before 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as nonalcoholic fatty liver disease) is increasing in the general population.

Rituximab for posttransplant lymphoproliferative disorder - therapeutic, preemptive, or prophylactic?

To minimize mortality due to posttransplant lymphoproliferative disorder (PTLD), the following strategies have been used: (1) Therapy without EBV Monitoring, i.e., administration of rituximab after PTLD diagnosis, usually by biopsy, in the absence of routine Epstein-Barr virus (EBV) DNAemia monitoring, (2) Prompt Therapy, i.

Complete Response to Donor Lymphocyte Infusion for Primary Hemophagocytic Lymphohistiocytosis Relapse after Allogeneic Hematopoietic Cell Transplantation.

Introduction: Primary hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory disorder characterized by dysregulation of inflammatory cells and cytokine signaling. Although first-line treatment consisting of immunosuppressive therapy and allogeneic hematopoietic cell transplantation (HCT) is often curative, it remains unknown whether any effective therapies exist for disease relapse/progression after HCT.

Case Presentation: Here we present a case of a 29-year-old male with primary HLH who failed HLH-94 protocol and subsequently underwent myeloablative HCT.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

Introduction: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown.

Corticosteroids as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplant recipients with calcineurin inhibitor intolerance.

Background Aims: Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance.

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review.

Although the use of allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) has declined with the development of novel targeted agents, it continues to play an important role for eligible patients with high-risk or heavily pretreated CLL who lack other treatment options. CLL is susceptible to a potent graft-versus-leukemia (GVL) effect which produces long-lasting remissions in 30-50% of transplanted patients. While allogeneic HCT is associated with significant risks of graft-versus-host disease (GVHD), infection, and non-relapse mortality (NRM), improvements in patient and donor selection, reduced intensity conditioning (RIC), GVHD prophylaxis, and supportive care have rendered this an increasingly safe and effective procedure in the current era.

Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma.

Although autologous stem cell transplantation (ASCT) can achieve durable responses in eligible patients with follicular lymphoma (FL), long-term follow-up is needed to determine if it has curative potential. This retrospective, multicenter study included 162 patients who received ASCT for relapsed FL in Alberta, Canada. With a median (range) follow-up time of 12.

Donor Genetic Predisposition to High Interleukin-10 Production Appears Protective against Acute Graft-Versus-Host Disease.

The persistence of graft-versus-host disease (GVHD) as the principal complication of allogeneic hematopoietic cell transplantation (HCT) demonstrates that HLA matching alone is insufficient to prevent alloreactivity. We performed molecular and functional characterization of 22 candidate cytokine genes for their potential to improve matching in 315 myeloablative, 10/10 HLA-matched donor−recipient pairs. Recipients of a graft carrying the -1082GG IL10 gene promoter region variant had a three-fold lower incidence of grade II−IV acute GVHD compared to IL10-1082AA graft recipients (SHR = 0.

Hematopoietic Cell Transplantation for Systemic Sclerosis-A Review.

Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality.

Rituximab Toxicity after Preemptive or Therapeutic Administration for Post-Transplant Lymphoproliferative Disorder.

Rituximab is commonly used as prevention, preemption, or therapeutically for post-transplant lymphoproliferative disorder (PTLD) after hematopoietic cell transplantation (HCT). Although it is generally assumed that rituximab toxicity (ie, infections resulting from hypogammaglobulinemia and neutropenia) is negligible in relation to mortality due to PTLD, limited evidence supports the validity of this assumption. We sought to determine the impact of rituximab on immunoglobulin levels, neutrophil count, infection density, and mortality outcomes.

Incomplete chimerism following myeloablative and anti-thymocyte globulin-conditioned hematopoietic cell transplantation is a risk factor for relapse and chronic graft-versus-host disease.

Background Aims: The value of routine chimerism determination after myeloablative hematopoietic cell transplantation (HCT) is unclear, particularly in the setting of anti-thymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis.

Methods: Blood samples were collected at 3 months post-HCT from 558 patients who received myeloablative conditioning and ATG-based GVHD prophylaxis. Chimerism was assessed using multiplex polymerase chain reaction of short tandem repeats in sorted T cells (CD3+) and leukemia lineage cells (CD13+CD33+ for myeloid malignancies and CD19+ for B-lymphoid malignancies).

Toward optimization of cyclosporine concentration target to prevent acute graft-versus-host disease following myeloablative allogeneic stem cell transplant.

Introduction: Despite the common use of cyclosporine (CsA) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic stem cell transplant, the optimal CsA trough target remains unknown.

Materials And Methods: Here, we report on outcomes of adult patients following myeloablative conditioning to identify an optimal CsA trough target and characterize the most relevant timeframe post-transplant for CsA trough targeting to minimize aGVHD. We retrospectively reviewed 399 consecutive patients who underwent first peripheral blood allogeneic stem cell transplant for hematological malignancies between January 2009 and December 2018.

Case Report: Chemotherapy-Associated Systemic Sclerosis: Is DNA Damage to Blame?

Systemic sclerosis, also known as scleroderma, is an autoimmune disease characterized by cutaneous and visceral fibrosis, immune dysregulation, and vasculopathy. Generally, the degree of skin fibrosis is associated with an increased likelihood of visceral organ involvement. Its pathogenesis is poorly understood; however, it is clear that changes in both the innate and adaptive immune responses are associated with fibroblast dysfunction and vascular damage.

Lymphocyte subset abnormalities in early severe scleroderma favor a Th2 phenotype and are not altered by prior immunosuppressive therapy.

Objectives: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial compared hematopoietic stem cell transplant to CYC treatment in patients with early SSc with progressive skin and lung or kidney involvement. Here we describe lymphocyte phenotype abnormalities at study entry and the relation to prior DMARD therapy.

Methods: Lymphocyte subsets (n = 26) measured by flow cytometry were compared in 123 heathy controls and 71 SCOT participants, including those given (n = 57) or not given (n = 14) DMARDs within 12 months of randomization.

Cumulative incidence of subsequent malignancy after allo-HCT conditioned with or without low-dose total body irradiation.

Subsequent malignancies (SMs) present a significant burden of morbidity and are a common cause of late mortality in survivors of allogeneic hematopoietic cell transplant (allo-HCT). Previous studies have described total body irradiation (TBI) as a risk factor for the development of SMs in allo-HCT survivors. However, most studies of the association between TBI and SM have examined high-dose TBI regimens (typically ≥600 cGy), and thus little is known about the association between low-dose TBI regimens and risk of SMs.

Impact of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation.

Background Aims: The internal tandem duplication of FLT3 (FLT3) and NPM1 mutations (NPM1) are well-established prognostic factors in cytogenetically intermediate-risk acute myeloid leukemia (AML) when treated with chemotherapy alone. However, their prognostic value in the setting of allogeneic hematopoietic cell transplantation (HCT) is controversial.

Methods: FLT3 and NPM1 mutational status was determined at diagnosis using single-gene polymerase chain reaction or next-generation sequencing in 247 adult patients with cytogenetically intermediate-risk AML who underwent myeloablative HCT.