Optimizing autologous nonmobilized mononuclear cell collections for cellular therapy in pediatric patients with high‐risk leukemia

Abstract

BACKGROUND:The manufacturing of cellular products for immunotherapy, such as chimeric antigen receptor T cells, requires successful collection of mononuclear cells. Collections from children with high-risk leukemia present a challenge, especially because the established COBE Spectra apheresis device is being replaced by the novel Spectra Optia device (Optia) in many institutions. Published experience for mononuclear cell collections in children with Optia is lacking. Our aim was to compare the two collection devices and describe modified settings on the Optia to optimize mononuclear cell collections. STUDY DESIGN AND METHODS:As a quality initiative, we retrospectively collected and compared data from mononuclear cell collections on both devices. Collected data included patient's clinical characteristics; collection parameters, including precollection lymphocyte/ CD3 counts, total blood volumes processed, runtimes, and side effects (including complete blood count and electrolyte changes); and product characteristics, including volumes and cell counts. Collection efficiencies and collection ratios were calculated. RESULTS:Twenty-six mononuclear cell collections were performed on 20 pediatric patients: 11 with COBE and 15 with Optia. Adequate mononuclear cell products were successfully collected with a single procedure from all patients except one, with mean calculated mononuclear cell collection efficiency that was significantly higher from Optia collections compared with COBE collections (57.9 6 4.6% vs 40.3 6 6.2%, respectively; p 5 0.04). CD3-positive yields were comparable on both machines (p 5 0.34) with significantly smaller blood volumes processed on Optia. Collected products had larger volumes on Optia. No significant side effects attributed to the procedure were noted. CONCLUSION:Mononuclear cell apheresis using the Optia device in children is more efficient and is as safe as that with the COBE device.T reating patients who have therapy-resistant or high-risk, relapsed acute lymphoblastic leukemia (ALL) is challenging.1,2 Cellular therapies using chimeric antigen receptor (CAR)-transfected T cells is currently being investigated as a promising new immunotherapeutic treatment modality.3 To manufacture CAR T cells, mononuclear cells (MNCs) from the patient need to be collected beforehand. 4 Recently, manufacturer support for the commonly used COBE Spectra (COBE) apheresis device has been discontinued, and many centers are replacing the COBE device with the new Spectra Optia (Optia) device (both from Terumo BCT). Both devices use centrifugation for blood separation, but they have different operating systems and collection techniques. The COBE device operates on manual color coordination, which requires intermittent manual interface control and repositioning by the operator based on the product color and aspect of the product aspired through the collect port. The Optia device, on the other hand, automates this process through an advanced automated interface management system, which provides constant feedback ...

Factors affecting lymphocyte collection efficiency for the manufacture of chimeric antigen receptor T cells in adults with B‐cell malignancies

“…Furthermore, our study did not demonstrate any difference in lymphocyte CE between the type of instrument used (Spectra Optia vs. COBE Spectra). This is in contrast to a retrospective study of 26 collections from pediatric patients 1.7 to 18 years old that showed a higher mean MNC CE2 from Spectra Optia versus COBE Spectra collections …”

“…The threshold of <40% was determined a priori to be the clinically meaningful outcome of lymphocyte CE based on our institutional criteria for minimum acceptable operator and instrument performance and a conservative estimate based on the published literature. [11][12][13][14][15] Potential predictors included the following: patientspecific factors such as age (every 10-year increase), sex (female vs. male), and weight (every 1-kg increase); diseasespecific factors such as disease type (ALL vs. chronic lymphocytic leukemia vs. non-Hodgkin lymphoma), prior therapy (every one additional line of therapy), prior autologous hematopoietic cell transplant and prior allogeneic hematopoietic cell transplant; precollection laboratory-specific factors such as granulocyte (every 0.1 × 10 3 /μL increase), lymphocyte (every 0.1 × 10 3 /μL increase), monocyte (every 0.1 × 10 3 /μL increase), hematocrit (every 1% increase) and platelet count (every 10 × 10 3 /μL increase); and collectionspecific factors such as type of venous access (central vs. peripheral) instrument (Spectra Optia vs. COBE Spectra), product total nucleated cell count (every 1 × 10 9 /μL increase) and product hematocrit (every 1% increase). Product total nucleated cell count and hematocrit were included as surrogates of collection quality and cellular interface management during the procedure.…”

“…Descriptive summary statistics included mean (standard deviation) and median (range) for continuous variables and number (percentage) for categorical variables. The threshold of <40% was determined a priori to be the clinically meaningful outcome of lymphocyte CE based on our institutional criteria for minimum acceptable operator and instrument performance and a conservative estimate based on the published literature …”

Lymphocyte apheresis for chimeric antigen receptor T‐cell manufacturing in children and young adults with leukemia and neuroblastoma

“…We previously reported a robust intent‐to‐treat product‐manufacturing success rate of 100% in minimally selected, heavily pretreated patients with ALL in our Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)‐02 study (http://www.clinicaltrials.gov identifier NCT02028455) . There are only two reports of lymphocyte apheresis in a heavily pretreated population with leukemia or neuroblastoma . Here, we report our experience in T‐cell collection via apheresis for CAR T‐cell manufacturing in pediatric and young adult patients with relapsed and refractory leukemia, lymphoma, and neuroblastoma.…”

“…7 There are only two reports of lymphocyte apheresis in a heavily pretreated population with leukemia or neuroblastoma. [14][15][16] Here, we report our experience in T-cell collection via apheresis for CAR T-cell manufacturing in pediatric and young adult patients with relapsed and refractory leukemia, lymphoma, and neuroblastoma.…”