Successful autologous hematopoietic stem cell transplants using Salmonella positive products collected from asymptomatic donors.

BACKGROUND: Bacterial contamination of hematopoietic stem cell (HSC) products is most commonly due to normal skin flora. Salmonella in HSC products is rare, and to our knowledge safe administration of an autologous HSC product containing Salmonella has not been reported. STUDY DESIGN AND METHODS: We describe two patients undergoing autologous HSC transplant: peripheral blood HSC collection was performed by leukapheresis, and samples were cultured according to standard institutional protocol. Subsequent microorganism identification was performed using MALDI-TOF (Bruker Biotyper). Strain-relatedness was investigated by infrared spectroscopy using the IR Biotyper (Bruker). RESULTS: The patients were asymptomatic throughout the collection process; however, HSC products collected on two consecutive days from each patient were positive for Salmonella. Isolates from both cultures were further characterized as Salmonella enterica serovar Dublin by the local public health department. Antibiotic susceptibility testing revealed different sensitivity patterns for the two strains. IR Biotyper demonstrated significant discriminatory power among the clinically significant Salmonella enterica subspecies, serogroups B, C1, and D. The patient strains were similar as both belonged to Group D Salmonella enterica serovar Dublin but were not identical. The Salmonella positive autologous HSC products were infused to both patients following administration of empiric antibiotic therapy. Both patients successfully engrafted and did well. CONCLUSION: Salmonella is rarely seen in cellular therapy products and positivity may be the result of asymptomatic bacteremia at the time of collection. We present two instances of autologous HSC products containing Salmonella that were infused, along with prophylactic antimicrobial therapy without significant adverse clinical effects.

Optimizing transfusion management of multiple myeloma patients receiving daratumumab-based regimens.

BACKGROUND: Daratumumab, a human anti-CD38 monoclonal antibody used to treat multiple myeloma, interferes with pretransfusion testing and can mask alloantibodies. Incidence of alloimmunization in patients on daratumumab has not been well characterized, and optimal transfusion guidelines regarding prophylactic antigen matching, accounting for both patient safety and efficiency, have not been well established for these patients. METHODS: Records of patients who received daratumumab between January 1, 2014 and July 2, 2019 were reviewed. Daratumumab interference with pretransfusion testing was managed by testing with reagent red blood cells (RBCs) treated with 0.2 M dithiothreitol. When daratumumab was present during antibody testing, patients were transfused with RBC units prophylactically matched for D, C, c, E, e, and K antigens per hospital policy. RESULTS: Out of 90 patients identified, 52 received a total of 638 RBC transfusions (average of 12.3 units per patient, SD 17.2, range 1-105, median 5 among those transfused). Alloantibodies existing before daratumumab initiation were identified in seven patients. No new alloantibodies were detected in any patients after starting daratumumab treatment. CONCLUSIONS: The incidence of alloimmunization in patients receiving daratumumab is low. Whether this is due to the effect of daratumumab, underlying pathophysiology, or other factors, is unknown. Because these patients require a large number of RBC transfusions overall and have little observed alloimmunization, phenotype matching (beyond RhD) may be unnecessary. Since the use of dithiothreitol cannot rule out the presence of anti-K, we recommend transfusion of ABO-compatible units, prophylactically matched for the D and K antigens only.

PREVALENCE OF MISMATCH REPAIR GENE MUTATIONS IN UVEAL MELANOMA.

PURPOSE: Uveal melanomas are associated with characteristic genetic changes. Germline mutations in mismatch repair (MMR) genes and microsatellite instability have been implicated in the development of numerous malignant neoplasms such as colon and ovarian cancers. The frequency of MMR defects in uveal melanomas has yet to be determined. METHODS: Here, we analyzed the frequency of MMR gene mutations in uveal melanoma specimens from the University of California, San Diego (UCSD), The Cancer Genome Atlas (TGCA), and the Catalogue of Somatic Mutations in Cancer (COSMIC). RESULTS: We identified only two mutations in a MMR gene: one premature stop codon in the PMS gene within the UCSD cohort (0.5% frequency) and one in-frame deletion in MSH3 within the COSMIC database (0.8% frequency). We report copy number variation of MLH1 in monosomy 3 and show decreased mRNA expression of MLH1 in uveal melanoma specimens with monosomy 3. Expression levels of MLH1 were not found to correlate with the observed number of total mutations. CONCLUSION: Overall, we show that mutations in MMR genes in uveal melanoma specimens are exceedingly rare, and although one copy of MLH1 is lost in monosomy 3, it does not seem to have pathologic consequences in uveal melanoma pathogenesis.