TECHNIQUES Modeling Leukemia with Human Induced Pluripotent Stem Cells
The reprogramming of human somatic cells into induced pluripotent stem cells (iPSCs) a little over a decade ago raised exciting prospects to transform the study and potentially also the therapy of human diseases. iPSC models have now been created for a multitude of hematologic diseases, including malignancies. Here we discuss practical aspects of iPSC modeling of malignant diseases, review recent studies, and discuss the new opportunities that iPSC models offer, as well as their current limitations and prospects for future development.
Risk stratification is a critical step when considering allogeneic hematopoietic stem cell transplantation (HSCT). While Lactate dehydrogenase (LDH) is a readily available biomarker with a prognostic role in the front-line therapy setting of hematological malignancies, its ’ role in the pretransplantation setting is undefined.
This study adds to the body of evidence in describing incidence and type of cardiac events experienced by an allogeneic and autologous HSCT population at one institution from 2012-2017. Sixty-five patients (9.8%) experienced cardiac events, including atrial arrhythmia (N = 39), acute heart failure (N = 9), acute coronary syndrome (N = 7), new onset hypertension (N = 9), with a few instances of bradycardia, ventricular arrhythmia, pericardial effusion, and pericarditis. Our multivariable regression analysis identified age (older), creatinine (higher) and history of coronary artery disease to significantly correlate with ris...
Publication date: Available online 9 January 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): James Nguyen, Navdeep Singh, Salma Afifi, Sergio Giralt, Mario E. Lacouture, Klaus J. Busam, Hani Hassoun
ConclusionsASCT can be safely performed even with lower HSC dose in non-cryopreserved setting.
In this report, we describe a case of significant hypopigmentation consistent with vitiligo, developing in a patient with multiple myeloma following autologous HSCT.
Data for 108 patients with multiple myeloma and lymphoma who received a stem cell dose less than 2 x 106/kg with those who received higher dose was compared.Neutrophil engraftment, platelet engraftment, length of hospital stay and incidence of proven bacterial infections were similar in both groups. ASCT can be safely performed even with lower HSC dose in non-cryopreserved setting.
Allogeneic hematopoietic cell transplantation (AHCT) represents the only curative therapy for many haematological malignancies. The graft-versus-leukemia effect (GVL), driven by donor Tcells plays a major role in its curative potential. This effect is sometimes very evident when AML and MDS relapses post AHCT are treated with donor lymphocyte infusions (DLI), in which lymphocytes from the original stem cell donor are infused, to augment an anti-tumor immune response or ensure that the donor stem cells remain engrafted, after the transplant.
Therapies targeting cell-surface antigens in acute myeloid leukemia (AML) have been tested over the past 20 years with limited improvement in overall survival. Recent advances in the understanding of AML pathogenesis support therapeutic targeting of leukemia stem cells as the most promising avenue toward a cure. In this review, we provide an overview of the evolving leukemia stem cell (LSC) model, including evidence of the cell of origin, cellular and molecular disease architecture, and source of relapse in AML. In addition, we explore limitations of current targeted strategies utilized in AML and describe the various immu...
Abstract Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approac...
Posttransplant lymphoproliferative disorder (PTLD), comprising a wide spectrum of lymphoid and plasmacytic proliferation, is a potentially fatal disorder arising after solid organ transplant (SOT) or hematopoietic stem cell transplant (HCT). The incidence of PTLD ranges from 0.07% (autologous) to as high as 29% (T cell depleted match unrelated donor) after HCT and is associated with Epstein-Barr virus (EBV) infection. 1,2 Impaired immune surveillance and pharmacologic immunosuppression are key factors in the pathogenies.