CD34-Selected Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Relapsed, High-Risk Multiple Myeloma.

We report results of a retrospective analysis of 44 patients with relapsed and high-risk multiple myeloma (MM) undergoing allogeneic CD34-selected hematopoietic stem cell transplantation (HSCT) from HLA-compatible donors. Patients had multiply relapsed disease including relapse at <15 months after autologous transplantation and most patients (28 of 44; 65%) also had high-risk cytogenetics. Before transplantation, patients received busulfan (.8 mg/kg × 10 doses), melphalan (70 mg/m(2) × 2 days), fludarabine (25 mg/m(2) × 5 days), and rabbit antithymocyte globulin (2.5 mg/kg × 2 days). Patients with 10/10 HLA- matched donors were treated prophylactically with low doses of donor lymphocyte infusions (.5 to 1 × 10(6) CD3(+)/kg) starting 4 to 6 months after CD34-selected HSCT. Acute (grade II to IV) graft-versus-host disease (GVHD) and transplantation-related mortality at 12 months were 2% and 18%, respectively. Chronic GVHD was not observed in any patient. Overall and progression-free survival at 2 years were 54% and 31%, respectively. By multivariate analyses, the outcomes of CD34-selected HSCT were influenced by presence of extramedullary disease, disease status before CD34-selected HSCT, and age. This study demonstrates notable safety and efficacy of CD34-selected HSCT in patients with multiply relapsed MM, including those with high-risk cytogenetics.

EBV Reactivation and Lymphomagenesis: More Questions than Answers.

PURPOSE OF REVIEW: Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus that affects almost all humans and establishes lifelong infections by infecting B-lymphocytes leading to their immortalization. EBV has a discrete life cycle with latency and lytic reactivation phases. EBV can reactivate and cause lymphoproliferation in both immunocompetent and immunocompromised individuals. There is sparse literature on monitoring protocols for EBV reactivation and no standardized treatment protocols to treat EBV-driven lymphoproliferation. RECENT FINDINGS: While there are no FDA-approved therapies to treat EBV, there are several strategies to inhibit EBV replication. These include immunosuppression reduction, nucleoside analogs, HDAC inhibitors, EBV-specific cytotoxic T-lymphocytes (CTLs), and monoclonal antibodies, such as rituximab. There is currently an open clinic trial combining the use of a HDAC inhibitor, nanatinostat, and ganciclovir to treat refractory/relapsed EBV lymphomas. Another novel therapy includes tabelecleucel, which is an allogenic EBV-directed T-cell immunotherapy that was approved by the European Medicines Agency, but is currently only available in the US for limited use in relapsed or refractory EBV-positive PTLD. Further research is needed to establish EBV monitoring protocols in high-risk populations, such as those with autoimmune disease, cancer, HIV, or receiving immunosuppressive therapy. Additionally, standardized treatments for both the prevention of EBV reactivation in high-risk populations and treatment of EBV reactivation and lymphoproliferation need to be established.

Pilot Trial of Homebound Hematopoietic Cell Transplantation.

For eligible patients with multiple myeloma (MM) and amyloid light chain (AL) amyloidosis, high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) is a standard and widely used consolidation therapy. Autologous HCT requires specialized care at a transplantation center and investment from patients and caregivers. We studied the safety and feasibility of delivering transplantation care in a homebound setting to decrease the burden of therapy and increase access to autologous HCT. Patients with MM and AL amyloidosis undergoing autologous HCT were eligible if they resided in designated ZIP codes and had a full-time caregiver, Wi-Fi connection, HCT Comorbidity Index ≤3, and Karnofsky Performance Status score ≥80. High-dose melphalan (on day -2) and hematopoietic cell reinfusion (day 0) were administered in the outpatient clinic. Protocol-specific home care was provided from day +1 through engraftment. Patients were assessed and blood was drawn daily by advanced practice providers. Interventions were delivered by registered nurses. Attending physicians communicated daily through telemedicine. Quality of life, patient and caregiver satisfaction, and fecal microbiota profiling data were collected. Fifteen patients were enrolled and received transplantation care at home starting on day +1 following hematopoietic cell infusion. Patients remained in the program for an average of 12 days and required an average of 2 outpatient visits while receiving home care. Seven of 15 patients were admitted for a median of 4 days (range, 3 to 10 days); admission occurred on day +7 in 5 patients, on day +8 in 1 patient, and on day +12 in 1 patient for neutropenic fever in 2 patients, fever attributed to engraftment syndrome in 2 patients, diarrhea in 2 patients, and dehydration in 1 patient. Only 1 patient had a documented infection (Clostridioides difficile). One patient admitted with neutropenic fever required intensive care unit admission for a gastrointestinal bleed. Forty-seven percent of the patients experienced a grade ≥3 nonhematologic toxicity. There were no deaths on the study. Patients and caregivers reported high satisfaction with care. Microbiota diversity patterns were similar to those of autologous HCT recipients who did not receive post-HCT care at home, although a subset of the cohort maintained microbiota diversity throughout. Homebound HCT in an urban setting is safe and feasible, with less than one-half of patients requiring inpatient admission. Despite increased patient and caregiver responsibility in the homebound setting compared with an inpatient setting, patient and caregiver satisfaction was high. These results support expansion of homebound transplantation care programs.