HLA-DR-DQ associations, combined with PLASMIC score, are reliable predictors of acquired thrombotic thrombocytopenic purpura (aTTP) and aid in differentiating aTTP from other thrombotic microangiopathies.

Background: Thrombotic microangiopathies (TMA) are a group of disorders with overlapping clinical features that require urgent intervention. Treatment is based on the recognition of the TMA type, which is often challenging. The aim of this study was to identify specific HLA associations with different TMA types to aid rapid diagnosis and appropriate treatment, since the HLA assay can be completed within five hours.

Barriers and facilitators to cord blood banking among pregnant women at a university obstetric clinic.

Background: Cord blood (CB) is a cell source for hematopoietic stem cell transplantation. In 2019, the percentage of births with CB collected for banking was only 3% nationally and 0.05% in our state.

A hands-on resident umbilical cord blood educational curriculum compared to online education of post-residency obstetricians: comparison of the volume of collected cord blood units.

Background: Umbilical cord blood unit (CBU) volume is a predictor of its later clinical utility. Many studies suggest the need to increase the volume of CBU collected, but most obstetrical providers receive no formal collection training.

Study Design And Methods: We designed and implemented an educational curriculum for obstetrics residents aimed at improving collection methods and increasing CBU volumes (CBUV).

Complement Regulatory Genetic Mutations in the Setting of Autoimmune Thrombotic Thrombocytopenic Purpura: A Case Series.

Objective: To explore the benefits of adding eculizumab for the treatment of refractory autoimmune thrombotic thrombocytopenic purpura (iTTP) with complement dysregulation.

Patients And Methods: From January 1, 2014, through July 1, 2017, we identified patients with iTTP defined by ADAMTS13 (disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels less than 5% and the presence of ADAMTS13 inhibitor. Patients who progressed after receiving standard of care management for iTTP were subjected to a comprehensive evaluation to look for evidence of complement activation.

ADAMTS13 Testing Methodologies and Thrombotic Thrombocytopenic Purpura (TTP): Conflicting Results Can Pose a Clinical Dilemma.

ADAMTS13 testing plays a critical role in confirming the clinical diagnosis of acquired idiopathic thrombotic thrombocytopenic purpura (TTP) and distinguishing it from other forms of thrombotic microangiopathies (TMA). Serial measurements of ADAMTS13 activity and inhibitor levels are also helpful in determining response to treatment and/or subsequent relapses. Numerous ADAMTS13 assays have been developed recently, including some with rapid turnaround times.

M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion.

Uncovering the cellular and molecular mechanisms by which hematopoietic stem cell (HSC) self-renewal is regulated can lead to the development of new strategies for promoting ex vivo HSC expansion. Here, we report the discovery that alternative (M2)-polarized macrophages (M2-MΦs) promote, but classical (M1)-polarized macrophages (M1-MΦs) inhibit, the self-renewal and expansion of HSCs from mouse bone marrow (BM) in vitro. The opposite effects of M1-MΦs and M2-MΦs on mouse BM HSCs were attributed to their differential expression of nitric oxide synthase 2 (NOS2) and arginase 1 (Arg1), because genetic knockout of and or inhibition of these enzymes with a specific inhibitor abrogated the differential effects of M1-MΦs and M2-MΦs.

Optia® continuous mononuclear collection (CMNC) system is a safe and efficient system for hematopoietic progenitor cells-apheresis (HPC-a) collection and yields a lower product hematocrit (HCT%) than the COBE® spectra system: A retrospective study.

Purpose: We evaluated the Optia® continuous mononuclear collection (CMNC) system for hematopoietic progenitor cell-apheresis (HPC-A) collection (Terumo BCT, Lakewood, CO) compared to the COBE® Spectra (Terumo BCT, Lakewood, CO), including both large volume leukapheresis (LVL) and non-LVL collections.

Methods: We performed a retrospective data analysis of all autologous HPC-A collections with the Optia® CMNC system (n = 93; LVL = 59, non-LVL = 34) since implementation at our institution and compared it with a similar number of concurrent collections utilizing the COBE® Spectra (n = 96; LVL = 68, non-LVL = 28). The population studied included multiple myeloma (62 patients/171 collections) and lymphoma (5 patients/18 collections).

Acetylsalicylic Acid During Leukapheresis Reduces the Incidence of Clotting in Hematopoietic Progenitor Cell Products.

Introduction: Clots may be seen during hematopoietic progenitor cell (HPC) collection or on product arrival to the cell therapy processing laboratory. We have always given one 81 mg acetylsalicylic acid (ASA) when clotting is seen during collection if there is no allergy, but hypothesized that the incidence of clotting would decrease if ASA was given to all autologous collectors with a platelet count of ≥80×10/L prior to collection (pre-emptively).

Methods: Autologous HPC were collected using the Spectra Optia instrument or Cobe Spectra instrument (Terumo BCT, Lakewood, CO) with heparinized citrate.

Percent cPRA (Calculated Panel Reactive Antibody) Value Predicts Percent of Positive Platelet Crossmatches.

Background: Platelet refractoriness or lack of platelet increase after platelet transfusion is seen in patients receiving chronic platelet transfusion support. Antibodies may develop against human platelet antigens (HPA) and/or against HLA class I antigens. Crossmatch (XM) compatible platelets or HLA-identical or HLA-compatible platelets are typically used to manage transfusion refractoriness.

Acquired thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome successfully treated with eculizumab.

Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine.

Flow Cytometric Panel-Reactive Antibody Results and the Ability to Find Transfusion-Compatible Platelets after Antibody-Desensitization for Allogeneic Bone Marrow Transplant.

Background: Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRA and Luminex based Single Antigen Bead (SAB)] would also correlate with the ability to find compatible platelets for allosensitized recipients.

Methods: A female patient with myelodysplastic syndrome and a high HLA class I PRA [>90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT.

Adverse Metaphase Cytogenetics Can Be Overcome by Adding Bortezomib and Thalidomide to Fractionated Melphalan Transplants.

To determine whether a reduction in the intensity of Total Therapy (TT) reduces toxicity and maintains efficacy. A total of 289 patients with gene expression profiling (GEP70)-defined low-risk multiple myeloma were randomized between a standard arm (TT4-S) and a light arm (TT4-L). TT4-L employed one instead of two inductions and consolidations.

Hemoglobin Variants Acquired Post-Exchange Transfusion in Pediatric Sickle Cell Disease (SCD) Patients.

Background: Many SCD patients receive chronic transfusions for prevention or treatment of disease related complications. Complications of the chronic transfusion noted in these patients include allergic reactions, transfusion transmitted infections, iron overload, and alloantibody formation. Even though hemoglobin (Hb) variants are prevalent in the general population, reports of transfusion-acquired Hb variants are rare.

Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients.

Highly activated/expanded natural killer (NK) cells can be generated by stimulation with the human leukocyte antigen-deficient cell line K562, genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence, and activity of expanded NK cells generated from myeloma patients (auto-NK) or haploidentical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone, and fludarabine.

Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs.

Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma.

Autologous graft versus host disease (autoGVHD) is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs) used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC) products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors.

Analysis of CD34+ cell collection using two mobilization regimens for newly diagnosed multiple myeloma patients reveals the separate impact of mobilization and collection variables.

Mobilization regimens for CD34+ cells have generally been judged successful based on the number of cells collected without evaluating mobilization separately from collection. Using retrospective data for patients who collected CD34+ cells on Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed mobilization and collection variables separately. A significant difference favoring MVDT-PACE was found in mean CD34+ cells/µL on day 2 of collection and in mean ratio of CD34+ cells/µL on day 2 to day 1.

Hematopoietic progenitor cell collection after autologous transplant for multiple myeloma: low platelet count predicts for poor collection and sole use of resulting graft enhances risk of myelodysplasia.

Collection of hematopoietic progenitor cells (HPC) after previous autologous hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with multiple myeloma (MM). With a total of 333 collections, the median number of CD34+ cells collected was 4.7 × 10(6) CD34+ cells/kg, and 74% of the patients collected ≥ 2.

Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma.

Lenalidomide has been linked to myelodysplastic syndrome (MDS) after autotransplants for myeloma. Total therapy trials (TT; TT2(-/+) thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide) offered the opportunity to examine the contribution of these immune-modulatory agents to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%.

Hematopoietic stem cell mobilization: a clinical protocol.

Autologous hematopoietic stem cell transplantation is the standard treatment for a wide variety of malignancies. At present, most hematopoietic progenitor/stem cell (HPC) collections are collected from the peripheral blood via leukapheresis following chemotherapy and/or growth factor-mediated mobilization. Most mobilization regimens consist of chemotherapy followed by one or more growth factors such as G-CSF, GM-CSF, or plerixafor.

A case of acquired dysfibrinogenemia in multiple myeloma treated with therapeutic plasma exchange.

A 70 year old Caucasian woman with IgG lamda multiple myeloma presented with uncontrollable bleeding from a bone marrow biopsy site which started days after the procedure. The patient was hyperviscous, and coagulation tests showed elevated activated partial thromboplastin time (aPTT) which was not corrected with a mixing study, elevated thrombin time and reptilase time, and possible inhibitors to Factors VIII and IX. Therapeutic plasma exchange was performed using plasma with corrections of plasma viscosity (1.

Osteogenic stimulatory conditions enhance growth and maturation of endothelial cell microvascular networks in culture with mesenchymal stem cells.

To optimize culture conditions for in vitro prevascularization of tissue-engineered bone constructs, the development of organotypic blood vessels under osteogenic stimulatory conditions (OM) was investigated. Coculture of endothelial cells and mesenchymal stem cells was used to assess proangiogenic effects of mesenchymal stem cells on endothelial cells. Four different culture conditions were evaluated for their effect on development of microvascular endothelial cell networks.