Identifying Candidates for Effective Utilization of Stored Autologous PBSCs in Salvage Transplantation for Multiple Myeloma: Who Benefits Most?

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.

Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma-type Richter syndrome.

Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P < .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.

Five-Lumen Antibiotic-Impregnated Femoral Central Venous Catheters in Severely Burned Patients: An Investigation of Device Utility and Catheter-Related Bloodstream Infection Rates.

The objective of this study is to determine the catheter-related bloodstream infection (CRBSI) rate in a severely burned patient population, many of whom required prolonged use of central venous catheters (CVCs). Between January 2008 and June 2012, 151 patients underwent placement of 455 five-lumen minocycline/rifampin-impregnated CVCs. CRBSI was defined as at least one blood culture (>100,000 colonies) and one simultaneous roll-plate CVC tip culture (>15 colony forming units) positive for the same organism. Most patients had accidental burns (81.5%) with a mean TBSA of 50%. A mean of three catheters were inserted per patient (range, 1-25). CVCs were inserted in the femoral vein (91.2%), subclavian vein (5.3%), and internal jugular vein (3.3%). Mean overall catheter indwell time was 8 days (range, 0-39 days). The overall rate of CRBSI per 1000 catheter days was 11.2; patients with a TBSA >60% experienced significantly higher rates of CRBSI than patients with a TBSA ≤60% (16.2 vs 7.3, P = .01). CVCs placed through burned skin were four times more likely to be associated with CRBSI than CVCs placed through intact skin. The most common infectious organism was Acinetobacter baumannii. Deep venous thrombosis developed in eleven patients (7%). The overall rate of CRBSI was 11.2, consistent with published rates of CRBSI in burn patients. Thus, femoral placement of 5-lumen CVCs did not result in increased CRBSI rates. These data support the safety of femoral CVC placement in burn patients, contrary to the Centers for Disease Control recommendation to avoid femoral CVC insertion.

Treating necrotizing fasciitis with or without hyperbaric oxygen therapy.

There is not enough clinical data to support the benefit of adjuvant HBO2 therapy for necrotizing fasciitis (NF). We retrospectively reviewed our 67 NF cases to compare the outcomes of adjuvant HBO2 therapy versus non-HBO2 therapy. The overall outcome and morbidity criteria were compared between a group of 29 NF patients who received the adjuvant HBO2 and a group of the remaining 38 NF patients treated by only surgery and other standards of care. This study did not find any difference between the groups in average length of hospital stay, and their mortality. However, six (25%) of the non-HBO2 group patients required amputation of extremities compared to one of the HBO2 group (Fisher exact p = 0.09). Although the benefit of adjuvant HBO2 therapy remains controversial for NF, and the outcomes of this study are not statistically significant, there is a trend in clinical outcomes which shows that the therapy has the potential to reduce the number of amputation and salvage extremities. These findings necessitate multicenter, prospective, case control study to assess the possible benefit of adjuvant HBO2 therapy for NF.

Purpura fulminans: a case series managed at a regional burn center.

Purpura fulminans (PF) is a protein C deficiency disease process with a high case fatality rate; however, overall incidence of the disease remains relatively very low. The similarity between skin necrosis secondary to PF and full-thickness skin burns provides the rationale for treating PF case in a burn center. In this case series we reviewed our experiences in managing PF and their associated favorable outcomes. Retrospective chart review of five PF cases managed between September 2004 and August 2006 at our Burn Center with 100% survival. Management of cases following the standard care of the Burn Center for a full-thickness burn included antibiotics, fluid resuscitation, surgical debridement with skin grafting, and activated protein C (Drotrecogin alfa) replacement. Two patients required amputations of extremities and all had surgical debridement. One required hemodialysis and two needed both hemodialysis and positive-pressure mechanical ventilator. No patient experienced any bleeding complications during or after surgery while receiving activated protein C. Early diagnosis and treatment at a burn center may reduce mortality and morbidity and loss of extremities in PF cases.