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Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting.

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as co…

Adolescent male fertility following reduced-intensity conditioning regimen for hematopoietic stem cell transplantation in non-malignant disorders.

INTRODUCTION: The effects of RIC for HSCT on male fertility remain unknown. We investigated spermatogenesis and gonadal hormonal status among adolescent male patients who received RIC HSCT for non-malignant diseases. PATIENTS AND METHODS: Patients with non-malignant disease who had undergone a RIC HSCT were recruited and evaluated for spermatogenesis via semen analysis and gonadal hormonal function via serum hormone levels. Those who had received prior chemotherapy or radiation were excluded from the study. We reviewed the charts to record demographic factors, conditioning regimen and complic

Allogeneic stem cell transplantation improves survival in relapsed Hodgkin lymphoma patients achieving complete remission after salvage treatment.

Allogeneic stem cell transplant (alloSCT) is a current treatment option for patients with refractory/relapsed classic Hodgkin lymphoma (CHL), including those who have failed an autologous transplantation. We performed a retrospective multicenter analysis of 113 patients (median age 28 years; range 14-56; 54% males) with refractory/relapsed (R/R) CHL who had undergone alloSCT in Argentina. Kaplan-Meier was used to estimate overall (OS) and progression-free survival (PFS). Relapse rate (RR) and non-relapse mortality (NRM) were estimated with cumulative incidence analysis. Disease status at trans

Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.

In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initia…

Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study.

BACKGROUND: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. METHODS: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-20…

Multistate modeling and simulation of patient trajectories after allogeneic hematopoietic stem cell transplantation to inform drug development.

We present a case study for developing clinical trial scenarios in a complex progressive disease with multiple events of interest. The idea is to first capture the course of the disease in a multistate Markov model, and then to simulate clinical trials from this model, including a variety of hypothesized drug effects. This case study focuses on the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). The patient trajectory after HSCT is characterized by a complex interplay of various events of interest, and there is no established best…

Use of Biosimilar Granulocyte Colony-Stimulating Factor for Mobilization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation.

The biologic medication filgrastim is approved by the Food and Drug Administration (FDA) to mobilize hematopoietic progenitor cells (HPCs) for collection by leukapheresis for autologous hematopoietic stem cell transplant (HSCT). The FDA-approved biologic tbo-filgrastim is currently used off-label for this indication in both autologous and allogeneic HSCT at the Tennessee Valley Healthcare System. The purpose of this review is to compare the efficacy of filgrastim and tbo-filgrastim for this indication. The primary outcomes were the proportion of autologous patients and allogeneic donors with a

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… | Autologous Hematopoietic Stem Cell Transplantation | Allogeneic Hematopoietic Stem Cell Transplantation Characteristic | Filgrastim ( N = 160) | Tbo-Filgrastim ( N = 207) | p -Value | Filgrastim ( N = 42) | Tbo-Filgrastim ( N = 60) | p -Value Age-years | 61 ± 8.4 | 61 ± 8.5 | 0.54 | 53 ± 12.0 | 48 … REFERENCES [1] Hatzimichael E Tuthill M Hematopoietic stem cell transplantation Stem Cells Cloning 2010 3 105 17 10.2147/SCCAA.S6815 24198516 PMC3781735 [2] D'Souza A Fretham C Current uses and outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR summary slides 2018 http://www.cibmtr.org [ …

Characterization of Viral Infections after Antithymocyte Globulin-Based Conditioning in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Antithymocyte globulin (ATG) has been shown to reduce the incidence of graft-versus-host-disease (GVHD) after matched related donor (MRD) and matched unrelated donor (MUD) hematopoietic stem cell transplantation (HCT); however, because of increased risks of infection and relapse, this use has not translated into a significant improvement in post-transplant survival. The goal of this single-center, retrospective cohort analysis was to quantify the incidence of viral reactivation and viral end-organ disease (EOD) within the first 100 days after MUD HCT with ATG-based conditioning compared with M…

Risks and Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Patients with HIV Infection.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies in persons living with HIV (PLHIV), however, uncertainties exist in many domains related to their care, including optimal donor selection, conditioning regimen, immunosuppression for graft-versus-host disease (GVHD), and long-term outcomes. We undertook a comprehensive systematic review from multiple databases to evaluate the foregoing uncertainties. The final sample comprised 49 patients (median age at HCT, 34 years; 46 males [93.8%]). Acute GVHD (aGVHD) was reported in 19 p…

Severe Herpes Zoster Requiring Intravenous Antiviral Treatment in Allogeneic Hematopoietic Cell Transplantation Recipients on Standard Acyclovir Prophylaxis.

Allogeneic hematopoietic cell transplantation (HCT) recipients are at increased risk for varicella zoster virus (VZV) reactivation and associated complications. The incidence, timing, and risk factors for severe herpes zoster (HZ) are not well described in the era of acyclovir (ACV) prophylaxis. We performed a retrospective cohort study of all patients who underwent first allogeneic HCT between October 2006 and December 2015 at our institution. Patients were followed until December 2017 for the development of severe HZ, defined as necessitating administration of i.v. antiviral medication. Out …

[Successful treatment with brentuximab vedotin maintenance therapy after autologous stem cell transplantation in high-risk Hodgkin lymphoma].

A 56-year-old woman was diagnosed with classical Hodgkin lymphoma in December 2012. She achieved complete remission (CR) with six cycles of … hosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen; therefore, autologous stem cell transplantation (ASCT) was performed. Because the dosing interval used for BV therapy was longer than that in the recommended schedule, we could not definitively attribute her recurrence to BV resistance. Moreover, she maintained a good performance status after rec …

Ocular chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in an Italian referral center.

PURPOSE: This study aimed to assess the prevalence and clinical manifestations of ocular graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: 269 patients who received allo-HSCT for hematologic malignancies were evaluated between December 2013 and April 2017 in this prospective observational study. Subjects underwent ophthalmologic examination at 6, 12 and 24 months after allo-HSCT. We evaluated the ophthalmologic and hematological data using the NIH consensus criteria definition and the International Chronic Ocular GVHD Consensus Gro…

Use of peripherally inserted central venous catheters (PICCs) in children receiving autologous or allogeneic stem-cell transplantation.

INTRODUCTION: The aim of our study was to present our experience with the use of peripherally inserted central catheters (PICCs) in pediatric patients receiving autologous or allogenic blood stem-cell transplantation. The insertion of the device in older children does not require general anesthesia and does not require a surgical procedure. METHODS: From January 2014 to January 2017, 13 PICCs were inserted as a central venous device in 11 pediatric patients submitted to 14 autologous or allogeneic stem-cell transplantation, at the Bone Marrow Transplant Unit of the Children's Hospital of Bres…

[The safety of decitabine as bridging pretreatment regimen before hematopoietic stem cell transplantation in pediatric hematological malignancies].

The safety of decitabine as bridging treatment before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with refractory hematological malignancies was evaluated. All 11 cases succeeded in hematopoietic reconstitution. The main adverse reaction was hematological toxicity. Neither did infections occur, nor drug-induced liver damage and renal impairment during decitabine administration. Most cases showed grade Ⅰ-Ⅱgastrointestinal adverse events. One case was diagnosed as severe acute graft versus host disease and died of intracranial hemorrhage on day 61 after allo-HSCT. …

Cardiac Rehabilitation in Patients With Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Cardio-oncology Pilot Project.

BACKGROUND: Worldwide > 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually. HSCT patients receive multiple cardiotoxic therapies (chemotherapy and radiation therapy) in addition to severe physical deconditioning during hospital admission. We hypothesized that guided exercise in a cardiac rehabilitation (CR) program following autologous HSCT is a safe and feasible intervention. METHODS: Pilot project to assess for safety, feasibility and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive patients with lymphoma underwent standard activity protocol

Viral Respiratory Tract Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients in the Era of Molecular Testing.

Viral respiratory tract infection (vRTI) is a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to assess the epidemiologic characteristics, risk factors, and outcomes of vRTI occurring in the period from conditioning to 100 days after allo-HSCT in the era of molecular testing. This study was a retrospective record review of patients who underwent allo-HSCT at Royal Melbourne Hospital between January 2010 and December 2015. Symptomatic patients were tested using respiratory multiplex polymerase c…

Impact of Toxicity on Survival for Older Adult Patients after CD34+ Selected Allogeneic Hematopoietic Stem Cell Transplantation.

Ex vivo CD34+ selection before allogeneic hematopoietic stem cell transplantation (allo-HCT) reduces graft-versus-host disease without increasing relapse but usually requires myeloablative conditioning. We aimed to identify toxicity patterns in older patients and the association with overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of 200 patients who underwent CD34+ selection allo-HCT using the ClinicMACS® system between 2006 and 2012. All grade 3 to 5 toxicities by CTCAE v4.0 were collected. Eighty patients aged ≥ 60 years with a median age of 64 (r…

Hospital-Level Variability in Broad-Spectrum Antibiotic Use for Children With Acute Leukemia Undergoing Hematopoietic Cell Transplantation.

OBJECTIVETo explore the prevalence and drivers of hospital-level variability in antibiotic utilization among hematopoietic cell transplant (HCT) recipients to inform antimicrobial stewardship initiatives.DESIGNRetrospective cohort study using data merged from the Pediatric Health Information System and the Center for International Blood and Marrow Transplant Research.SETTINGThe study included 27 transplant centers in freestanding children's hospitals.METHODSThe primary outcome was days of broad-spectrum antibiotic use in the interval from day of HCT through neutrophil engraftment. Hospital ant

Hypothermia broadens the therapeutic time window of mesenchymal stem cell transplantation for severe neonatal hypoxic ischemic encephalopathy.

Recently, we have demonstrated that concurrent hypothermia and mesenchymal stem cells (MSCs) transplantation synergistically improved severe neonatal hypoxic ischemic encephalopathy (HIE). The current study was designed to determine whether hypothermia could extend the therapeutic time window of MSC transplantation for severe neonatal HIE. To induce HIE, newborn rat pups were exposed to 8% oxygen for 2 h following unilateral carotid artery ligation on postnatal day (P) 7. After approving severe HIE involving >50% of the ipsilateral hemisphere volume, hypothermia (32 °C) for 2 days was started.

Donor Polymorphisms in Genes Related to B-Cell Biology Associated With Antibody-Mediated Rejection After Heart Transplantation.

BACKGROUND: Heart transplantation (HT) is a well-established lifesaving treatment for endstage cardiac failure. Antibody-mediated rejection (AMR) represents one of the main problems after HT because of its diagnostic complexity and the poor evidence for supporting treatments. Complement cascade and B-cells play a key role in AMR and contribute to graft damage. This study explored the importance of variants in genes related to complement pathway and B-cell biology in HT and AMR in donors and in donor-recipient pairs. METHODS AND RESULTS: Genetic variants in 112 genes (51 complement and 61 B-ce