Clonal hematopoiesis-derived therapy-related myeloid neoplasms after autologous hematopoietic stem cell transplant for lymphoid and non-lymphoid disorders.

Therapy-related myeloid neoplasms (tMN) are complications of cytotoxic therapies. Risk of tMN is high in recipients of autologous hematopoietic stem cell transplantation (aHSCT). Acquisition of genomic mutations represents a key pathogenic driver but the origins, timing and dynamics, particularly in the context of preexisting or emergent clonal hematopoiesis (CH), have not been sufficiently clarified.

Authentic leadership at the Cleveland Clinic: psychological safety in the midst of crisis.

Objectives: The goal of this research was to examine the leadership experiences of senior leaders at the Cleveland Clinic during the recent COVID-19 pandemic crisis. A secondary goal was to examine lessons that could inform other healthcare organisations as they move into subsequent crisis situations.

Design: The authors examined publicly available podcast transcripts where interviewees shared their leadership experiences on the Cleveland Clinic Beyond Leadership Podcast.

Health-Related Quality-of-Life Comparison of Adult Related and Unrelated HSC Donors: An RDSafe Study.

Multiple investigations have documented the health-related quality-of-life (HRQoL) and donation-related experiences of unrelated donors (URDs), but similar investigations of the related donor (RD) experience have been less common. The central goal of this study was to longitudinally examine and compare HRQoL of RD and URD hematopoietic stem cell (HSC) donors from predonation through 1 year postdonation. This prospective investigation included adult HSC donors ages 18 to 60 years who donated bone marrow or peripheral blood stem cells at one of 48 geographically diverse US transplant/donor centers and completed HRQoL interviews at predonation and 4 weeks and 1 year postdonation.

Therapeutic Dose Monitoring of Busulfan Is Associated with Reduced Risk of Relapse in Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Optimal administration of busulfan (Bu) is hampered by variable and unpredictable drug metabolism in individual patients. At our institution, Bu was previously administered with fixed weight-based dosing (WBD) in combination with cyclophosphamide (Cy) and etoposide (E) for patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). In 2014, we adopted real-time pharmacokinetic (PK)-guided therapeutic drug monitoring (TDM) of Bu for all NHL patients undergoing Bu-containing ASCT.

Conditional Long-Term Survival after Autologous Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma.

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for patients with chemosensitive, relapsed, diffuse large B cell lymphoma (DLBCL). We performed a retrospective cohort study to delineate subsequent (conditional) and relative survival in 371 adult patients with DLBCL who underwent AHCT between 2000 and 2014 and had survived for 1, 2, 3, or 5 years after transplant. The probability of overall survival at 10 years after AHCT was 62%, 71%, 77%, and 86%, respectively, for the 4 cohorts, whereas that of progression-free survival (PFS) was 55%, 65%, 72%, and 81%, respectively.

Clinical Factors Associated With Cost in Head and Neck Cancer: Implications for a Bundled Payment Model.

Purpose: To determine which factors influence cost in head and neck cancer (HNC) to inform the development of a bundled payment model (BPM).

Methods: Patients with stages 0 to IVB (by American Joint Commission on Cancer, 7th edition) HNC of various sites and histology treated definitively at a single tertiary care center during 2013 were included. Clinical variables and direct cost data were obtained, and their associations were investigated using χ, , Wilcoxon rank sum, and analysis of variance testing.

BEAM or BUCYVP16-conditioning regimen for autologous stem-cell transplantation in non-Hodgkin's lymphomas.

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) is an effective salvage therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL). However, the optimal conditioning regimen is unclear. Different conditioning regimens prior to AHCT have been used with the two most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide).

BEAM versus BUCYVP16 Conditioning before Autologous Hematopoietic Stem Cell Transplant in Patients with Hodgkin Lymphoma.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) is a standard of care for patients with relapsed Hodgkin lymphoma. Different conditioning regimens before AHSCT have been used, with the 2 most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We retrospectively compared the outcomes of patients treated with BEAM (n = 128) or BUCYVP16 (n = 105) followed by AHSCT.

Higher Risks of Toxicity and Incomplete Recovery in 13- to 17-Year-Old Females after Marrow Donation: RDSafe Peds Results.

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age <18 years at 25 pediatric transplantation centers in North America, assessing them predonation, peridonation, and at 1 month, 6 months, and 1 year postdonation. We noted that 71% of children reported pain and 59% reported other symptoms peridonation, with resolution to 14% and 12% at 1 month postdonation.

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study.

Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at one year compared to unrelated donors.

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America.

Precision Oncology in Solid Tumors: A Longitudinal Tertiary Care Center Experience.

Purpose: Precision oncology is widely discussed, but cohort studies are limited. We previously reported our prospective experience of precision oncology in solid tumors, and here we report our longitudinal experience, focusing on therapeutic impact.

Patients And Methods: We conducted a retrospective review of 600 consecutive patients seen at Cleveland Clinic from 2013 to 2016 for treatment of incurable solid tumor malignancies for whom tumor genomic profiling was ordered using FoundationOne (Cambridge, MA).

Effect of bone marrow CD34+cells and T-cell subsets on clinical outcomes after myeloablative allogeneic hematopoietic cell transplantation.

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses.

Prognostic Factors for Mortality among Day +100 Survivors after Allogeneic Hematopoietic Cell Transplantation.

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation.

Efficacy of Standard Dose R-CHOP Alternating With R-HDAC Followed by Autologous Hematopoietic Cell Transplantation as Initial Therapy of Mantle Cell Lymphoma, a Single-Institution Experience.

Background: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone.

Patients And Methods: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC.

Neutropenic fever during peripheral blood progenitor cell mobilization is associated with decreased CD34+ cell collection and increased apheresis collection days.

Background: Peripheral blood progenitor cell (PBPC) mobilization with chemotherapy in addition to Granulocyte-Colony Stimulating Factor (G-CSF) improves cell collection compared to G-CSF alone; however, it is associated with increased risk of neutropenic fever (NF).

Methods: We analyzed risk factors for post-priming NF and NF association with autologous stem cell transplant outcomes. Between 1998 and 2008, 593 adult patients with lymphoma underwent PBPC mobilization with etoposide and G-CSF.