Cryopreservation of Allogeneic Hematopoietic Cell Products During COVID-19 Pandemic: Graft Characterization and Engraftment Outcomes.

BACKGROUND: The COVID-19 pandemic triggered the deployment of unfamiliar measures to safeguard successful allogeneic hematopoietic cell transplantation (allo-HCT). Among these measures, cryopreservation offered logistical benefits that could outlast the pandemic, including graft availability and timely clinical service. The purpose of this study was to evaluate graft quality and hematopoietic reconstitution in patients transplanted with cryopreserved allogeneic stem cell products during the COVID-19 pandemic. METHODS: We evaluated 44 patients who underwent allo-HCT using cryopreserved grafts consisting of hematopoietic progenitor cells (HPC) apheresis (A) and bone marrow (BM) products at Mount Sinai Hospital. Comparative analyses of 37 grafts infused fresh during the one-year period preceding the pandemic were performed. Assessment of cellular therapy products included total nucleated cell and CD34+ cell enumeration, viability, and post-thaw recovery. The primary clinical endpoint was the evaluation of engraftment (absolute neutrophil count [ANC] and platelet count) and donor chimerism (presence of CD33+ and CD3+ donor cells) at day +30 and +100 post-transplant. Adverse events related to cell infusion were also analyzed. RESULTS: Patient characteristics were comparable between the fresh and cryopreserved groups with 2 exceptions in the HPC-A cohort: the number of patients in the cryopreserved group that received haploidentical grafts was 6 times that in the fresh group, and the number of patients in the fresh group with a Karnofsky performance score >90 was double that in the cryopreserved group. The quality of HPC-A and HPC-BM products was not affected by cryopreservation, and all grafts met the release criteria for infusion. The pandemic did not affect the time between collection and cryopreservation (median, 24 hours) and time in storage (median, 15 days). Median time to ANC recovery was significantly delayed in recipients of cryopreserved HPC-A (15 vs 11 days, P = .0121), and there was a trend toward delayed platelet engraftment (24 vs 19 days, P = .0712). The delay in ANC and platelet recovery was not observed when only matched graft recipients were compared. Cryopreservation did not affect the ability of HPC-BM grafts to engraft and reconstitute hematopoiesis, and there was no difference in the rates of ANC and platelet recovery. Achievement of donor CD3/CD33 chimerism was not affected by cryopreservation of either HPC-A or HPC-BM products. Graft failure was observed in only 1 case, a recipient of cryopreserved HPC-BM. Three recipients of cryopreserved HPC-A grafts died before ANC engraftment from infectious complications. Remarkably, 22% of our studied population had myelofibrosis, and almost half received cryopreserved HPC-A grafts with no graft failure observed. Finally, patients receiving cryopreserved grafts were at a higher risk of infusion-related adverse events than those receiving fresh grafts. CONCLUSIONS: Cryopreservation of allogeneic grafts results in adequate product quality with minimal impact on short-term clinical outcomes, except for an increased risk of infusion-related adverse events. Cryopreservation is a safe option in terms of graft quality and hematopoietic reconstitution with logistical benefits, but additional data are needed to determine long-term outcomes and assess whether this is a suitable strategy for at-risk patients.

Bridging advanced myeloma patients to subsequent treatments and clinical trials with classical chemotherapy and stem cell support.

Rapidly progressing relapsed/refractory multiple myeloma (RRMM) patients with compromised marrow have limited treatment options. Thus, non-myeloablative chemotherapy with a stem cell boost (SCB) may provide disease control and hematopoietic improvement as bridge to subsequent therapies. We identified 96 patients who received a SCB between January 2011 and December 2019 at the Mount Sinai Hospital. Patients had a median age of 64 years, received a median of 7 prior lines of therapy and 68 and 42% were triple-class and penta-drug refractory, respectively. Chemotherapy included melphalan (MEL) (n = 16), melphalan + carmustine (BCNU/MEL) (n = 52) or a variant of DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) (n = 28). Median time to neutrophil recovery was 10 days and was significantly lower with DCEP (8 days) compared to MEL and BCNU/MEL (10-11 days) (p = 0.0047). Time to progression, progression-free survival and overall survival were 3.19, 2.7 and 8.38 months, respectively. The BCNU/MEL group had the highest response rate of 85% (p = 0.05), clinical benefit rate of 94% (p = 0.0014), progression-free survival of 3.3 months (p = 0.4) and overall survival of 8.7 months (p = 0.5). Sixty-six patients (69%) were bridged to new lines of therapy, including clinical trials. Non-myeloablative chemotherapy with SCB provides rapid disease control and marrow recovery with potential to receive further therapy.

Quality Improvement in Hematopoietic Stem Cell Transplant and Cellular Therapy: Using the Model for Improvement to impact Outcomes.

Quality improvement and quality assurance form a complementary and independent relationship. Quality assurance measures compliance against industry standards using audits, whereas quality improvement is a continuous process focused on processes and systems that can improve care. The Model for Improvement is a robust quality improvement tool that transplant and cellular therapy teams can use to redesign healthcare processes. The Model for Improvement uses several components addressed in sequence to organize and critically evaluate improvement activities. Unlike other health sciences clinical research, quality improvement projects, and research are based on dynamic hypotheses that develop into observable, serial tests of change with continuous collection and feedback of performance data to stakeholders.

A case of syngeneic graft-versus-host disease.

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

Concept analysis: resilience.

This paper will systematically analyze the concept of resilience using an integrated review of literature. The historical perspective, attributes, antecedents, and consequences of resilience will be reviewed. A theoretical and operational definition will be provided. The Walker and Avant method will be used to describe the cases. Finally, the use of concept map will capture the relationships among the attributes, antecedents, consequences, and empirical indicators through clustering and chaining.