Prognostic implication of pre-transplant FEV on long-term outcomes following allogeneic hematopoietic stem cell transplantation.

Background: Pre-transplant pulmonary function testing (PFT) is essential before allogeneic hematopoietic stem cell transplant (HCT), yet the optimal cutoff value for affecting transplant outcomes remains poorly defined.

Study Design: Retrospective analysis of pre-HCT PFT data from 605 consecutive patients at the Princess Margaret Cancer Centre between January 1, 2004 and December 31, 2013 used binary recursive partitioning to identify cutoff values for overall survival (OS) as an endpoint of transplant outcomes. These values were compared to HCT comorbidity index (HCT-CI) FEV cutoffs for OS, cumulative incidence of relapse and non-relapse mortality.

Targeted recruitment of optimal donors for unrelated hematopoietic cell transplantation: The Stem Cell Club process.

Objective/background: Patients in need of hematopoietic stem cell transplantation often cannot find a suitable HLA-matched donor in their families and rely on unrelated donors. Individuals can register with their country's donor registry either online or at a stem cell drive by providing consent and a tissue sample for typing.

Methods: Stem Cell Club is a donor recruitment organization in Canada that recruits Canadians as stem cell donors.

Safety of two-hour intermittent intravenous infusions of tacrolimus in the allogeneic hematopoietic stem cell transplantation unit.

At our institution, tacrolimus is used as a second-line agent for the prevention and treatment of graft-versus-host-disease in the allogeneic hematopoietic stem cell transplantation (HSCT) unit after patients have experienced a serious or intolerable adverse event to cyclosporine. As per our standard practice, tacrolimus is administered via 2-h intermittent IV infusions (IIVs) every 12 h rather than continuous IV infusion. Shorter infusion times are cautioned due to concerns of higher rates of nephrotoxicity, neurotoxicity and infusion-related reactions, although there is a paucity of data to support this claim.

First Ready, First to Go: Ethical Priority-Setting of Allogeneic Stem Cell Transplant at a Major Cancer Centre.

Medical advancements have now made it possible to provide allogeneic stem cell transplantation (allo-SCTs) to older patients and use stem cells from less well-matched donors. This has resulted in access to a life-saving modality for a greater number of patients with imminent life-threatening illnesses. However, resources have not always kept pace with innovation and expanded volumes.

Predictors of the trajectory of cognitive functioning in the first 6 months after allogeneic hematopoietic stem cell transplantation.

Certain subgroups of patients may be particularly vulnerable to cognitive decline after treatment with allogeneic hematopoietic stem cell transplant (HCT). The objective of this study was to identify predictors of cognitive functioning changes within the first 6 months after HCT. Fifty-eight adults treated with allogeneic HCT (53% male, mean 48 years of age) completed neuropsychological tests of learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory at three time points: pre-HCT and day 100 and 6 months post transplant.

Combination of the Centre for International Blood and Marrow Transplant Registry Risk Score and the Global Severity Score Enhances Prognostic Risk Stratification in Patients Receiving Frontline Therapy for Chronic Graft-versus-Host Disease.

The Centre for International Blood and Marrow Transplant Registry (CIBMTR) score has been shown to be prognostic for overall survival (OS) and nonrelapse mortality (NRM) but has been shown in several single-center studies to classify a large proportion of patients with chronic graft-versus-host disease (cGVHD) in the lower risk groups (RG1 to RG2), thereby limiting its prognostic utility for those patients. We evaluate the CIBMTR score, the Global Severity Score (GSS), and a novel risk score developed to improve on the limitations of the CIBMTR with respect to clinically relevant outcomes, including failure-free survival (FFS), in patients receiving frontline systemic treatment for cGVHD. We identified 277 patients between 2002 and 2012 at the Princess Margaret Cancer Centre in Toronto, Canada, who developed cGVHD and were treated with at least 1 line of systemic therapy.

Equally Interchangeable? How Sex and Gender Affect Transplantation.

Organ transplantation as an option to overcome end-stage diseases is common in countries with advanced healthcare systems and is increasingly provided in emerging and developing countries. A review of the literature points to sex- and gender-based inequity in the field with differences reported at each step of the transplant process, including access to a transplantation waiting list, access to transplantation once waitlisted, as well as outcome after transplantation. In this review, we summarize the data regarding sex- and gender-based disparity in adult and pediatric kidney, liver, lung, heart, and hematopoietic stem cell transplantation and argue that there are not only biological but also psychological and socioeconomic issues that contribute to disparity in the outcome, as well as an inequitable access to transplantation for women and girls.

Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML.

Objective: In individuals with cytogenetically normal (CN) AML, disease risk is estimated using molecular features such as the status of NPM1 and FLT3-ITD genes. However, data regarding the impact of NPM1 and FLT3-ITD status on hematopoietic stem cell transplant (HCT) outcomes are limited. We examined the effect of NPM1 and FLT3-ITD status on transplant outcomes in 131 CN AML patients transplanted at Princess Margaret Hospital between 2006 and 2017.

Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability.

Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myelogenous leukemia (AML); however, a major cause of treatment failure is disease relapse. The purpose of this single-center Phase I study was to determine the safety and tolerability of administration of the CXCR4 inhibitor plerixafor (Mozobil; Sanofi Genzyme) along with myeloablative conditioning in patients with AML undergoing allogeneic HCT. The rationale was that plerixafor may mobilize leukemic stem cells, making them more susceptible to the conditioning chemotherapy (registered at ClinicalTrials.

Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies.

Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD.

Fludarabine and busulfan plus low-dose TBI as reduced intensity conditioning in older patients undergoing allogeneic hematopoietic cell transplant for myeloid malignancies.

We have been using a combination of fludarabine/busulfan plus low-dose total body irradiation (TBI) as the reduced-intensity conditioning (RIC) regimen for patients age ≥ 60 years undergoing allogeneic hematopoietic cell transplantation (HCT) for myeloid malignancies. We retrospectively analyzed outcomes of 116 older patients (median age 64 years) who underwent HCT from 2006 to 2015 for myeloid malignancies, including acute myeloid leukemia (AML) in first complete remission (CR1). On univariate analysis, overall survival (OS) for the cohort at 3 years was 33% (95% CI 25-42).

Efficacy of Cidofovir in Treatment of BK Virus-Induced Hemorrhagic Cystitis in Allogeneic Hematopoietic Cell Transplant Recipients.

BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada.

Quality of life trajectories during the first year following hematopoietic cell transplantation: an inception cohort study.

Background: Allogeneic hematopoietic cell transplantation (HCT) affects quality of life (QOL). Patient-reported outcomes examine symptoms, side effects, distress, and physical and social problems, but positive outcomes have been ignored. This inception cohort study followed people over the first year following HCT to document positive and negative outcomes.

Outcome following second allogeneic hematopoietic cell transplantation: A single-center experience.

Objective: Second allogeneic hematopoietic cell transplantation (HCT) may be indicated following relapse or graft failure following first HCT. Our retrospective single-center study sought to investigate parameters that influence post-second allogeneic HCT survival.

Method: We investigated 92 patients who underwent second allogeneic HCT between 1980 and 2016 for relapse or graft failure following first HCT.

Impact of comorbidities constituting the hematopoietic cell transplant (HCT)-comorbidity index on the outcome of patients undergoing allogeneic HCT for acute myeloid leukemia.

Objective: To investigate the prognostic impact of the individual component comorbidities of the hematopoietic cell transplant comorbidity index (HCT-CI) in patients with acute myeloid leukemia (AML) that underwent allogeneic hematopoietic cell transplant (HCT).

Method: This single-center study retrospectively investigated the individual comorbidities of the HCT-CI on the outcome of 418 patients that underwent HCT for AML, in CR1 (n = 303, 72%) or CR2 (n = 115, 28%) at our center between 1999 and 2014.

Results: Median age at HCT was 50 years (range 18-71).

Incidence and Risk Factors for Nontuberculous Mycobacterial Infection after Allogeneic Hematopoietic Cell Transplantation.

Allogenic hematopoietic stem cell transplant (HCT) recipients are at risk of many infections. Nontuberculous mycobacteria (NTM) are increasingly recognized as clinically significant pathogens in this population. We investigated the incidence and risk factors for NTM infection after allogeneic HCT.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

Background: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing.

Extramedullary disease at diagnosis of AML does not influence outcome of patients undergoing allogeneic hematopoietic cell transplant in CR1.

Objective: Extramedullary disease (EMD) at diagnosis of acute myeloid leukemia (AML) has been associated with increased risk of relapse and worse outcomes post-chemotherapy. This study sought to investigate the association of EMD with outcomes following allogeneic hematopoietic cell transplantation (allo-HCT).

Methods: This single-center retrospective study investigated the impact of EMD at diagnosis on the outcome of patients transplanted for AML in first complete remission (CR1).

Distinctive clinical characteristics and favorable outcomes in patients with large granular lymphocytosis after allo-HCT: 12-year follow-up data.

An increase in large granular lymphocytes (LGL) is frequently seen in patients following allogeneic hematopoietic cell transplantation (allo-HCT) and it has been associated with better outcomes in some reports. We assessed 826 consecutive patients at our institution with over 12 years of follow-up for the occurrence of LGL lymphocytosis after allo-HCT. The 3-year cumulative incidence of LGL lymphocytosis was 14.

Progressive multifocal leukoencephalopathy due to John Cunningham (JC) virus following allogeneic haematopoietic cell transplantation.

Progressive multifocal leukoencephalopathy (PML) is an uncommon infectious complication post allogeneic stem cell transplant. We present a case report of a patient developing this complication with a review of the current literature. It also describes the first use of artesunate in a clinical case of PML with no beneficial effect.

Long-Term Incidence of Secondary Malignancies after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience.

To review the emergence of secondary malignancies (SMs) in recipients of allogeneic hematopoietic cell transplantation (HCT), we documented the occurrence of SMs in 2415 allogeneic HCT recipients, ages 18 to 71, in a single center over 4 decades. SMs were seen in 209 patients, including 58 with nonmetastatic squamous cell (SCC) and basal cell carcinoma (BCC) of the skin. Cumulative incidence of SM was 6.

Improved prognostic stratification power of CIBMTR risk score with the addition of absolute lymphocyte and eosinophil counts at the onset of chronic GVHD.

The CIBMTR chronic graft-versus-host disease (cGVHD) risk score can be refined and improved for better prognostic stratification. Three hundred and seven consecutive patients diagnosed with cGVHD by the NIH consensus criteria were retrospectively reviewed and had the CIBMTR risk score applied and analyzed. The CIBMTR risk score was successfully validated in our cohort (n = 307).