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Role of Stem-Cell Transplantation in Leukemia Treatment.

Stem cells (SCs) play a major role in advanced fields of regenerative medicine and other research areas. They are involved in the regeneration of damaged tissue or cells, due to their self-renewal characteristics. Tissue or cells can be damaged through a variety of diseases, including hematologic and nonhematologic malignancies. In regard to this, stem-cell transplantation is a cellular therapeutic approach to restore those impaired cells, tissue, or organs. SCs have a therapeutic potential in the application of stem-cell transplantation. Research has been focused mainly on the application of …

History of hematopoietic cell transplantation: challenges and progress.

After more than 60 years of research in allogeneic hematopoietic cell transplantation (HCT), this therapy has advanced from one that was declared dead in the 1960s to a standard treatment of otherwise fatal malignant and non-malignant blood diseases. To date, close to 1.5 million hematopoietic cell transplants have been performed in more than 1,500 transplantation centers worldwide. This review will highlight the enormous efforts by numerous investigators throughout the world who have brought the experimental field of HCT to clinical reality, examine ongoing challenges, and provide insights fo…

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

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… Incorporating placental tissue in cord blood banking for stem cell transplantation. Expert Rev Hematol (2018) 11:649–61. 10.1080/17474086.2018.1483717 11. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. … Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheumatic Dis (2010) 69:1423–9. 10.1136/ard.2009.123463 47. Zhao K, Lou R, Huang F, Peng Y, Jiang Z, Huang K, et al. …

[Allogeneic hematopoietic stem cell transplantation using posttransplant cyclophosphamide].

Posttransplant cyclophosphamide (PTCy) was initially developed by the Johns Hopkins group as a graft-versus-host disease (GVHD) prophylaxis for human leukocyte antigen (HLA)-haploidentical stem cell transplantation. Recently, PTCy has been attempted in HLA-matched transplantation. In HLA-haploidentical hematopoietic transplantation, several retrospective studies have compared HLA-matched transplantation with HLA-haploidentical hematopoietic transplantation using PTCy. In these reports, transplantation outcomes have been comparable. Therefore, PTCy- based haploidentical transplantation is a via…

Retinal stem cell transplantation: Balancing safety and potential.

Stem cell transplantation holds great promise as a potential treatment for currently incurable retinal degenerative diseases that cause poor vision and blindness. Recently, safety data have emerged from several Phase I/II clinical trials of retinal stem cell transplantation. These clinical trials, usually run in partnership with academic institutions, are based on sound preclinical studies and are focused on patient safety. However, reports of serious adverse events arising from cell therapy in other poorly regulated centers have now emerged in the lay and scientific press. While progress in s…

Acute kidney injury in hematopoietic stem cell transplantation.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in the setting of hematopoietic stem cell transplantation (HSCT) is common in pediatric and adult patients. The incidence ranges from 12 to 66%, and development of AKI in the posttransplant course is independently associated with higher mortality. RECENT FINDINGS: Patients who undergo HSCT have many risk factors for developing AKI, including sepsis, use of nephrotoxic medications, graft versus host disease (GVHD), and veno-occlusive disease (VOD). In addition, engraftment syndrome/cytokine storm, transplant-associated thrombotic microangiopathy (TA…

Hematopoietic Cell Transplantation for MHC Class II Deficiency.

Major histocompatibility complex (MHC) class II deficiency is a rare and fatal primary combined immunodeficiency. It affects both marrow-der … II molecules on affected cell types which is the immunologic hallmark of the disease. Hematopoietic cell transplantation (HCT) is the only established curative therapy for MHC class II deficiency but it is difficult as affected children have significant comorbidities at the time of HCT. Optimization organ function, implementing a reduced toxicity conditioning regimen, …

Haematopoietic Stem Cell Transplantation for Primary Haemophagocytic Lymphohistiocytosis.

Haematopoietic stem cell transplantation currently remains the only curative treatment of primary forms of haemophagocytic lymphohistiocytosis (HLH). Rapid diagnosis, efficient primary treatment of hyperinflammation, and conditioning regimens tailored to this demanding condition have substantially improved prognosis in the past 40 years. However, refractory hyperinflammation, central nervous system (CNS) involvement, unavailability of matched donors, susceptibility to conditioning-related toxicities, and a high frequency of mixed chimaerism remain a challenge in a substantial proportion of pat…

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.

BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score compari…

Infectious Keratitis After Ocular Surface Stem Cell Transplantation.

PURPOSE: To describe the rate, clinical/microbiological characteristics, and outcomes of infectious keratitis in eyes with limbal stem cell deficiency after ocular surface stem cell transplantation (OSST). METHODS: In this retrospective chart review of 278 eyes that underwent OSST between January 2006 and December 2016, eyes treated for previous infectious keratitis (bacterial, fungal, or viral) were included. Demographics, risk factors, course, microbiological characteristics, and outcomes were assessed. RESULTS: A total of 52 eyes (18.7%) of 48 patients (28 men and 20 women) developed 75 e…

Autologous haematopoietic stem cell transplantation for neurological diseases.

Neuroinflammatory diseases such as multiple sclerosis, neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis are leading causes of physical disability in people of working age. In the last decades significant therapeutic advances have been made that can ameliorate the disease course. Nevertheless, many affected will continue to deteriorate despite treatment, and the costs associated with disease-modifying drugs constitute a significant fiscal burden on healthcare in developed countries. Autologous haematopoietic stem cell transplantation is a treatment a…

ABO Incompatibility and Hematopoietic Stem Cell Transplantation Outcomes.

Introduction: The increased risk of hemolytic reactions and erythrocyte recovery delay in ABO incompatible hematopoietic stem cell transplantation (HSCT) are well established. Effects of ABO incompatibility on other transplantation outcomes are evaluated in this study. Subjects and Methods: We prospectively followed 501 patients undergoing allogeneic stem cell transplantation regarding their ABO compatibility groups for a median time of 34.7 months. Patients were studied in minor, major and bidirectional mismatched and matched groups. Results: Mean survival time (OS) was lower in minor mismatc…

Acute Respiratory Failure After Hematopoietic Stem Cell Transplantation

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… An Update on Pulmonary Complications of Hematopoietic Stem Cell Transplantation. … Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091–2101. doi: 10.1056/NEJMoa1004383. 4. Chi AK, Soubani AO, White AC, Miller KB. An update on pulmonary complications of hematopoietic stem cell transplantation. …

Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation.

BACKGROUND: Cytomegalovirus (CMV) infection remains a common complication after allogeneic hematopoietic-cell transplantation. Letermovir is an antiviral drug that inhibits the CMV-terminase complex. METHODS: In this phase 3, double-blind trial, we randomly assigned CMV-seropositive transplant recipients, 18 years of age or older, in a 2:1 ratio to receive letermovir or placebo, administered orally or intravenously, through week 14 after transplantation; randomization was stratified according to trial site and CMV disease risk. Letermovir was administered at a dose of 480 mg per day (or 240 m…

[Early immune reconstitution after hematopoietic stem cell transplantation].

OBJECTIVE: To search for differences in early immune reconstitution after allogenic or autologous hematopoietic stem cell transplantation (HSCT). METHODS: The peripheral blood (PB) from 31 adult patients undergoing allogenic HSCT (allo-HSCT, 15 patients) or autologous HSCT (auto-HSCT, 16 patients) for the treatment of hematological malignancies and from 20 related healthy controls (HC) from December 2011 to August 2014 was used to analyze the kinetic recovery of lymphocyte subsets by means of flow cytometry during 12 months after HSCT. The T cell receptor rearrangement excision circle (TREC) …

Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms.

Cell-based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types are being tested as possible routes to tolerance induction, in the absence of donor-derived stem cells. Early data with each

Cytomegalovirus Infection after CD34(+)-Selected Hematopoietic Cell Transplantation.

The effectiveness of preemptive treatment (PET) for cytomegalovirus (CMV) in recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) by CD34(+) selection is not well defined. We analyzed 213 adults who received TCD-HCT at our institution from June 2010 through May 2014. Patients were monitored by a CMV quantitative PCR assay if recipient (R) or donor (D) were CMV seropositive. CMV viremia occurred early (median, 27 days after HCT) in 91 of 213 (42.7%) patients for a 180-day cumulative incidence of 84.5%, 61.8%, and 0 for R+/D+, R+/D-, and R-/D+ patients, respective…

Herpes zoster after autologous hematopoietic stem cell transplantation.

BACKGROUND: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. METHODS: A retro…

Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation.

Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [(3)H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the a…

Aspergillus Thyroiditis after Allogeneic Hematopoietic Stem Cell Transplantation.

Aspergillus thyroiditis is a rare disorder detected in immunocompromised patients during disseminated infections. Early management is essential to prevent high mortality. A 61-year-old allogeneic stem cell male recipient presented with painful thyroid nodular enlargement. He had low TSH and low free T4 levels. The thyroid ultrasound showed a hypoechoic nodule; biopsy indicated suppurative Aspergillus thyroiditis. He was successfully treated by amphotericin B.