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Background: Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions., Methods: Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite. Product quality was assessed before and after processing for volume, RBC and leukocyte content; RBC-depletion and stem cell (CD34+ cells) recovery was calculated there from. Clinical engraftment data were collected from 26/45 allogeneic recipients., Results: Median RBC removal was 98.2% (range 90.8-99.1%), median CD34+ cell recovery was 93.6%, minimum recovery being 72%, total product volume was reduced to 7.5% (range 4.7-23.0%). Products engrafted with expected probability and kinetics. Performance indicators were stable over time., Discussion: Spectra Optia BMC is a robust and efficient technology for RBC-depletion and volume reduction of BM, providing near-complete RBC removal and excellent CD34+ cell recovery.

Background: Red blood cell (RBC) depletion is a standard technique for preparation of ABO-incompatible bone marrow transplants (BMTs). Density centrifugation or apheresis are used successfully at clinical scale. The advent of a bone marrow (BM) processing module for the Spectra Optia (Terumo BCT) provided the initiative to formally compare our standard technology, the COBE2991 (Ficoll, manual, "C") with the Spectra Optia BMP (apheresis, semiautomatic, "O"), the Sepax II NeatCell (Ficoll, automatic, "S"), the Miltenyi CliniMACS Prodigy density gradient separation system (Ficoll, automatic, "P"), and manual Ficoll ("M"). C and O handle larger product volumes than S, P, and M., Study Design and Methods: Technologies were assessed for RBC depletion, target cell (mononuclear cells [MNCs] for buffy coats [BCs], CD34+ cells for BM) recovery, and cost/labor. BC pools were simultaneously purged with C, O, S, and P; five to 18 BM samples were sequentially processed with C, O, S, and M., Results: Mean RBC removal with C was 97% (BCs) or 92% (BM). From both products, O removed 97%, and P, S, and M removed 99% of RBCs. MNC recovery from BC (98% C, 97% O, 65% P, 74% S) or CD34+ cell recovery from BM (92% C, 90% O, 67% S, 70% M) were best with C and O. Polymorphonuclear cells (PMNs) were depleted from BCs by P, S, and C, while O recovered 50% of PMNs. Time savings compared to C or M for all tested technologies are considerable., Conclusion: All methods are in principle suitable and can be selected based on sample volume, available technology, and desired product specifications beyond RBC depletion and MNC and/or CD34+ cell recovery., (© 2015 AABB.)

The bone marrow (BM) hematopoietic system (HS) gives rise to blood cells originating from hematopoietic stem cells (HSCs), including megakaryocytes (MKs) and red blood cells (erythrocytes; RBCs). Many steps of the cell-fate decision remain to be elucidated, being important for cancer treatment. To explore the role of Wnt/β-catenin for MK and RBC differentiation, we activated β-catenin signaling in platelet-derived growth factor b (Pdgfb)-expressing cells of the HS using a Cre-lox approach (Ctnnb1BM-GOF). FACS analysis revealed that Pdgfb is mainly expressed by megakaryocytic progenitors (MKPs), MKs and platelets. Recombination resulted in a lethal phenotype in mutants (Ctnnb1BM-GOFwt/fl, Ctnnb1BM-GOFfl/fl) 3 weeks after tamoxifen injection, showing an increase in MKs in the BM and spleen, but no pronounced anemia despite reduced erythrocyte counts. BM transplantation (BMT) of Ctnnb1BM-GOF BM into lethally irradiated wildtype recipients (BMT-Ctnnb1BM-GOF) confirmed the megakaryocytic, but not the lethal phenotype. CFU-MK assays in vitro with BM cells of Ctnnb1BM-GOF mice supported MK skewing at the expense of erythroid colonies. Molecularly, the runt-related transcription factor 1 (RUNX1) mRNA, known to suppress erythropoiesis, was upregulated in Ctnnb1BM-GOF BM cells. In conclusion, β-catenin activation plays a key role in cell-fate decision favoring MK development at the expense of erythroid production. [ABSTRACT FROM AUTHOR]

Summary: ABO incompatibility affects approximately 40% of allogeneic stem cell transplants in Caucasian patient populations. Because bone marrow (BM), the preferred graft from paediatric sibling donors and for non‐malignant diseases, has a red blood cell (RBC) content similar to blood, anti‐donor isoagglutinins must either be depleted from the recipient or RBCs removed from the graft. To achieve tolerability of unmanipulated BM grafts, we used controlled infusions of donor ABO‐type RBC units to deplete isoagglutinins before the transplant. This retrospective study evaluates the outcomes of 52 ABO major incompatible BM transplants performed at our centre between 2007 and 2019. The use of donor‐type RBC transfusions was well tolerated. They effectively reduced isoagglutinins levels, typically achieving target titres after one (60%) or two (29%) transfusions. The approach allowed for successful and uneventful infusions of unmanipulated BM which provided timely engraftment. The transplant outcomes were not inferior to those of a matched‐pair control group of patients with ABO‐identical donors. [ABSTRACT FROM AUTHOR]

Background: The ability to approximate intra-operative hemoglobin loss with reasonable precision and linearity is prerequisite for determination of a relevant surgical outcome parameter: This information enables comparison of surgical procedures between different techniques, surgeons or hospitals, and supports anticipation of transfusion needs. Different formulas have been proposed, but none of them were validated for accuracy, precision and linearity against a cohort with precisely measured hemoglobin loss and, possibly for that reason, neither has established itself as gold standard. We sought to identify the minimal dataset needed to generate reasonably precise and accurate hemoglobin loss prediction tools and to derive and validate an estimation formula.Methods: Routinely available clinical and laboratory data from a cohort of 401 healthy individuals with controlled hemoglobin loss between 29 and 233 g were extracted from medical charts. Supervised learning algorithms were applied to identify a minimal data set and to generate and validate a formula for calculation of hemoglobin loss.Results: Of the classical supervised learning algorithms applied, the linear and Ridge regression models performed at least as well as the more complex models. Most straightforward to analyze and check for robustness, we proceeded with linear regression. Weight, height, sex and hemoglobin concentration before and on the morning after the intervention were sufficient to generate a formula for estimation of hemoglobin loss. The resulting model yields an outstanding R2 of 53.2% with similar precision throughout the entire range of volumes or donor sizes, thereby meaningfully outperforming previously proposed medical models.Conclusions: The resulting formula will allow objective benchmarking of surgical blood loss, enabling informed decision making as to the need for pre-operative type-and-cross only vs. reservation of packed red cell units, depending on a patient's anemia tolerance, and thus contributing to resource management. [ABSTRACT FROM AUTHOR]

Background and Objectives: Red blood cell (RBC) transfusions are needed by almost every acute myeloid leukaemia (AML) patient undergoing induction chemotherapy and constitute a cornerstone in supportive measures for cancer patients in general. Randomized controlled trials have shown non‐inferiority or even superiority of restrictive transfusion guidelines over liberal transfusion guidelines in specific clinical situations outside of medical oncology. In this study, we analysed whether more restrictive RBC transfusion reduces blood use without affecting hard outcomes. Materials and Methods: A total of 352 AML patients diagnosed between 2007 and 2018 and undergoing intensive induction chemotherapy were included in this retrospective analysis. In the less restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 8 g/dl (2007–2014). In the restrictive transfusion group, patients received RBC transfusion for haemoglobin levels below 7 g/dl (2016–2018). Liberal transfusion triggers were never endorsed. Results: A total of 268 (76·1%) and 84 (23·9%) AML patients fell into the less restrictive and restrictive transfusion groups, respectively. The less restrictive transfusion group had 1 g/dl higher mean haemoglobin levels, received their first RBC transfusions earlier and needed 1·5 more units of RBC during the hospital stay of induction chemotherapy. Febrile episodes, C‐reactive protein levels, admission to the intensive care unit, length of hospital stay as well as response and survival rates did not differ between the two cohorts. Conclusion: From our retrospective analysis, we conclude that a more restrictive transfusion trigger does not affect important outcomes of AML patients. The opportunity to test possible effects of the more severe anaemia in the restrictive transfusion group on quality of life was missed. [ABSTRACT FROM AUTHOR]

The article responds to concerns raised by Drs. Haspel and McKenna regarding the safety and tolerability of ABO major mismatched red blood cell (RBC) transfusion in bone marrow transplantation. The authors acknowledge the risks associated with graft manipulation and provide examples of instances where the graft was compromised during RBC depletion. They also note that not all transplant services have access to efficient RBC depletion technology. However, they argue that ABO major mismatched RBC transfusion can be beneficial in certain cases, particularly when small donors or recipients are involved. They highlight their own observations of reduced mortality in isoagglutinin-depleted recipients and express their intention to further explore the effects of ABO major mismatch with isoagglutinin depletion in future studies. [Extracted from the article]

During erythropoiesis, haematopoietic stem cells (HSCs) differentiate in successive steps of commitment and specification to mature erythrocytes. This differentiation process is controlled by transcription factors that establish stage- and cell type-specific gene expression. In this study, we demonstrate that FUSE binding protein 1 (FUBP1), a transcriptional regulator important for HSC self-renewal and survival, is regulated by T-cell acute lymphocytic leukaemia 1 (TAL1) in erythroid progenitor cells. TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation. The binding of TAL1 to the FUBP1 promoter is highly dependent on an intact GATA sequence in a combined E-box/GATA motif. We found that FUBP1 expression is required for efficient erythropoiesis, as FUBP1-deficient progenitor cells were limited in their potential of erythroid differentiation. Thus, the finding of an interconnection between GATA1/TAL1 and FUBP1 reveals a molecular mechanism that is part of the switch from progenitor- to erythrocyte-specific gene expression. In summary, we identified a TAL1/FUBP1 transcriptional relationship, whose physiological function in haematopoiesis is connected to proper erythropoiesis. [ABSTRACT FROM AUTHOR]

Background Donor granulocyte concentrates are routinely administered to patients with granulocyte function defects or transient neutropenia and (risk of) bacterial or fungal exacerbations, despite lack of definitive clinical proof for patient-relevant outcome improvement. Granulocytes are collected by apheresis from healthy donors treated with granulocyte-colony-stimulating factor and/or steroids for neutrophil mobilization the evening before apheresis, as well as with hydroxyethyl starch during apheresis, to enhance sedimentation of red blood cells (RBCs) and thus to facilitate accessibility of neutrophils for collection. Study Design and Methods Granulocyte apheresis procedures are performed with standard apheresis equipment, including with the frequently used apheresis system for peripheral blood 'stem cell' collection, COBE Spectra MNC (Terumo BCT), using the same tubing set as for MNC collection, but a different software protocol, PMN. An automated apheresis system for granulocyte collection, Spectra Optia IDL (Terumo BCT), became available in October 2011. Since then, 70 granulocyte apheresis procedures have been performed at our site, 35 each with the new and old systems. Results Apheresis procedures were well tolerated throughout. The target dose of 1 × 1010 neutrophils was achieved in all but one collection with Spectra Optia IDL. Spectra Optia IDL collections were approximately 20% more efficient. Products contained more nontarget white blood cells (mononuclear cells), but fewer RBCs and platelets. Although less blood had to be processed with Spectra Optia IDL to achieve the same granulocyte dose, clinically relevant differences between the two apheresis devices were not apparent. Conclusion Both apheresis systems are similarly capable of generating granulocyte concentrates. [ABSTRACT FROM AUTHOR]