Despite the global vaccination campaigns, certain patient groups remain highly vulnerable to SARS-CoV-2 and are at high risk for unfavorable COVID-19 outcomes. As previously shown by our group and a more recent report by Chang Su and coworkers, patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT) represent one of such high-risk populations. This is due to the underlying disease-related immunodeficiency, suboptimal response to vaccines, heavy exposure to dexamethasone, and the use of high-dose melphalan prior to the ASCT procedure. Contracting SARS-CoV-2 and developing COVID-19 during the ASCT procedure remain high-risk events for these patients. It is then crucial to maintain and implement all appropriate strategies to prevent COVID-19 breakthroughs in this clinical setting. This might include targeted pre- and post-exposure prophylaxis with monoclonal antibodies, based on the circulation and prevalence of different SARS-CoV-2 variants/subvariants, and the prompt use of antivirals if, despite prophylaxis, MM patients develop COVID-19 during the transplantation procedure. We emphasize the importance of regularly monitoring MM patients for SARS-CoV-2 infection at all stages of the ASCT procedure. This is crucial to promptly implement measures to reduce the risk of unfavorable COVID-19 outcomes during the current post-pandemic phase.

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT\'s efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.

Aim: Atypical teratoid rhabdoid tumor (ATRT) is a rare and highly aggressive primary CNS neoplasm, predominantly observed in children. The use of autologous stem cell transplantation (ASCT) in pediatric ATRT has shown promise; however, its utility in adult ATRT remains unclear. Patients & methods: This study presents the case of an adult patient with ATRT who is in remission after ASCT and reviews the literature on ASCT in adults with ATRT. Four cases of ATRT in adults who underwent ASCT were identified, with pertinent data summarized. Results: All five patients survived longer than the historical average survival rate, four of whom had no clinical or radiographic evidence of disease at the final follow-up. Conclusion: Based on limited data, there may be a role for ASCT in the treatment of adults with ATRT.
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BACKGROUND: Autologous stem cell transplantation (ASCT) is a well-established consolidation treatment for many hematologic cancers which delivers prolonged survival. A subset of patients\' adequate stem cell harvest is not achievable with a solitary use of granulocyte colony-stimulating agents (G-CSF). Generally, chemomobilization is employed for patients failing G-CSF and its most feared complication febrile neutropenia (FN).
METHODS: Here, we aimed to investigate the impact of the FN in chemomobilization on apheresis outcomes and engraftment. One hundred and eighty-three patients with the diagnosis of lymphoma or myeloma who underwent chemomobilization between 2015 and 2020 were included in the study.
RESULTS: Forty-three patients experienced FN. All patients received G-CSF. All myeloma patients were mobilized with 4 g/m2 cyclophosphamide, but it was heterogeneous for lymphoma patients. The precollection blood counts, harvested CD34+ hematopoietic stem cells (HSCs)/kg, apheresis count, and engraftment durations were recorded. Preapheresis leukocyte and platelet were lower in the FN group (P = 0,004 and P = 0,001). Peripheral CD34 HSCs and total harvested CD34 HSCs were similar among groups (P = 0.25 and P = 0.9). More apheresis was needed in the FN group, but it was not significant (P = 0.07). Undergoing ASCT was similar (P = 0.7); however, platelet and neutrophil engraftment durations were slower in the FN group (P = 0.05 and P = 0.001).
CONCLUSIONS: Harvesting sufficient CD34+ HSCs from patients with FN is still feasible; however, FN treatment should begin promptly, and further apheresis sessions may be required.

BACKGROUND: Lenalidomide (R), bortezomib (V), and dexamethasone (d) is a standard-of-care regimen in newly diagnosed multiple myeloma (NDMM); however, characteristics and outcomes for nontransplanted patients receiving frontline RVd are not well understood.
METHODS: The ConnectⓇ MM Registry is a large, US, multicenter, prospective observational cohort study of NDMM patients.
METHODS: This analysis investigated characteristics and outcomes of patients who received RVd alone or followed by Rd or R (RVd ± Rd/R) who did not undergo frontline autologous stem cell transplantation.
RESULTS: As of August 2021, 314 of 1979 nontransplanted patients received RVd ± Rd/R as initial therapy. Of these, 135 were aged ≤ 65 years and 179 were > 65 years. 108 patients had time to relapse (TTR) of ≤ 12 months and 182 had TTR > 12 months. Baseline characteristics were comparable regardless of TTR and age group except renal function, which was more commonly impaired in older patients. Among patients aged ≤ 65 and > 65 years, median duration of first-line treatment was 6.3 and 9.0 months, median time to next line for those who received second-line therapy was 15.5 and 15.2 months, median progression-free survival (PFS) was 19.3 and 23.0 months, and median overall survival was 60.0 and 59.1 months, respectively. High-risk disease (per IMWG criteria) and high serum calcium were associated with higher hazard of progression or death; the adjusted PFS hazard ratio with respect to age (≤ 65 vs. > 65 years) based on multivariable analysis was 1.18 (0.89-1.57; P = .25).
CONCLUSIONS: These results indicate RVd is active across age groups and provide a better understanding of outcomes with RVd in NDMM.

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%-10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C-reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow-up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q-SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it\'s still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

OBJECTIVE: High-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT) improves the prognosis in pediatric patients with several solid tumors and lymphomas. Little is known about the reconstitution of the immune system after ASCT and the influence of CD34+ cell selection on the reconstitution in pediatric patients.
METHODS: Between 1990 and 2001, 94 pediatric patients with solid tumors and lymphomas received autologous CD34+ selected or unmanipulated peripheral stem cells after HDC. CD34+ selection was carried out with magnetic microbeads. The absolute numbers of T cells, B cells and natural killer (NK) cells were measured and compared in both groups at various time points post-transplant.
RESULTS: Recovery of T cells was significantly faster in the unmanipulated group at day 30, with no significant difference later on. Reconstitution of B and NK cells was similar in both groups without significant differences at any time. The CD34+-selected group was divided into patients receiving less or more than 5.385 × 106/kg CD34+ cells. Patients in the CD34+ high-dose group displayed significantly faster reconstitutions of neutrophiles and lymphocyte subsets than the CD34+ low-dose group.
CONCLUSIONS: Engraftment and reconstitution of leukocytes, B cells and NK cells after transplantation of CD34+ selected stem cells were comparable to that in patients receiving unmanipulated grafts. T-cell recovery was faster in the unmanipulated group only within the first month. However, this delay could be compensated by transplantation of >5.385 × 106 CD34+ cells/kg. Especially for patients receiving immunotherapy after HDC large numbers of immune effector cells such as NK and T cells are necessary to mediate antibody-dependent cellular cytotoxicity. Therefore, in patients receiving autologous CD34+-selected grafts, our data emphasize the need to administer high stem cell counts.

Recently, CD19-directed chimeric antigen receptor (CAR) T-cell therapies have revolutionized treatment strategies for diffuse large B-cell lymphoma (DLBCL). CAR T-cell therapy is increasingly used as a second-line therapy for patients with DLBCL with early relapse or refractoriness to initial chemoimmunotherapy and displaced high-dose chemotherapy, followed by autologous stem cell transplantation (ASCT) as the standard of care for these patients. However, patients with late relapse or chemosensitive disease still benefit from autologous stem cell transplantation. We will review practice-changing studies in early relapse (ZUMA-7 and TRANSFORM) under consideration of the negative BELINDA trial, with a focus on register data, comparing CAR T-cell therapy and ASCT for patients responding to salvage therapy.

Increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a common complication associated with acute care hospitalization among older adults. To estimate the prevalence and prognostic significance of HAD among older adults with MM undergoing ASCT. This retrospective cohort study used consecutive adults ≥ 18 y with PCD receiving ASCT at a single institution between 1/2013 and 5/2023. Trained nursing staff assessed Katz Activities of Daily Living (ADL) at admission and every 3 days thereafter under our Virtual Acute Care for Elders program. The primary outcome was development of HAD defined as ≥1 point decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We examined the association between putative risk factors such as age, Karnofsky performance status (KPS), baseline ADL score, Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and HAD using modified Poisson regression models with robust variance estimators. Subsequently, we studied the impact of HAD on downstream adverse events including 30-day readmission rates and long term survival. We included 778 adults with a median age of 62 y (QR 56-68 y), with 56% males and 55% non-Hispanic Whites. In the overall population, 112 (14.4%) developed HAD, with much higher incidence among older adults ≥ 65 y compared to those <65 y at ASCT (22% vs. 9%, P value < .01). In multivariable analysis, increasing age (RR 1.56; 95% CI 1.25-1.94, per 10 y increase), female sex (RR 1.79; 95% CI 1.27-2.53) and KPS ≤ 70 (RR 2.55; 95% CI 1.32-4.94) were associated with an increased risk of developing HAD. As compared to those without, patients with HAD had a two-fold higher risk of 30-day readmission (95% CI 1.16-3.39) and a 3.7-fold increased risk of all-cause mortality (95% CI 2.15-6.22). Nearly one in 4 older adults ≥ 65 y developed HAD while undergoing ASCT which was associated with a two-fold increased risk of 30-day readmission. Interventions to prevent HAD and its downstream consequences are critically needed.