Kimberly W. Sanford

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen‐specific cellular immunity

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza‐Rev and cryopreserved. Subsequent stem cell mobilization was followed by high‐dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up‐regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)‐specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.

Fecal occult blood testing.

Colorectal cancer (CRC) is the third most common cancer in the United States. A reduction in cumulative mortality occurs when patients are routinely screened by fecal occult blood tests (FOBT) and early lesions are removed. These point-of-care tests detect minute amounts of blood released from precancerous and cancerous colon lesions. Positive test results should be followed up with complete diagnostic testing to treat precancerous lesions and diagnose patients at earlier stages of cancer, thereby increasing overall survival. More complex assays are designed to detect genetic changes in cells released from malignant and even premalignant lesions. This article provides information on the screening and diagnostic tests available for CRC detection as well as the advantages and disadvantages of each.

Extracorporeal photopheresis: Clinical use so far

Extracorporeal photopheresis (ECP or photopheresis) is an advanced therapeutic apheresis procedure in which blood is separated into its various components and the isolated buffy coat is treated with 8‐methoxypsoralen (a photoactivating drug), exposed to ultraviolet light and returned to the patient. All other remaining blood components are also returned to the patient. The purpose of this procedure is immunomodulation. The treated leukocytes, specifically T‐cells, are returned to the patients circulation and will induce cytotoxicity and reduce proliferation of new T‐cells. In the United States, ECP was initially approved for the treatment of cutaneous T‐cell lymphoma by the US Food and Drug Administration in the late 1980s. Since that time, it has been used as an “off‐label” therapy to treat several other autoimmune diseases in the United States and even more extensively in Europe and Asia. The following review is limited to the current clinical use of ECP in cutaneous T‐cell lymphoma, Crohns disease, systemic sclerosis, graft versus host disease, and emerging data on nephrogenic systemic fibrosis. J. Clin. Apheresis, 2012.

Therapeutic apheresis in special populations

Rasheed A. Balogun,* Adesola Ogunniyi, Kimberly Sanford, Chidi Okafor, Peter I. Lobo, Ghodrat Siami, John Barcia, and Andre A. Kaplan Department of Medicine, Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia Department of Medicine, University of Ibadan, Nigeria Department of Pathology, Virginia Commonwealth University, Richmond, Virginia Department of Medicine, Vanderbilt University, Nashville, Tennessee Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut Department of Pediatrics, University of Virginia, Charlottesville, Virginia

Harvesting autologous stem cells from a patient with red blood cell abnormalities of β-thalassemia intermedia

Autologous stem cell transplants in patients with hemoglobinopathies are limited. Previous reports used granulocyte–colony‐stimulating factor (G‐CSF) for mobilization of stem cells; there are no reported cases undergoing plerixafor mobilization. We report such a patient, providing guidance for peripheral blood stem cells collection when aberrant red blood cells (RBCs) disrupt normal separation.

Detection and Significance of Donath-Landsteiner Antibodies in a 5-year-old Female Presenting With Hemolytic Anemia

Donath-Landsteiner (DL) antibodies are immunoglobulins formed in response to a viral, bacterial, or spirochete infection and are capable of inducing Paroxysmal Cold Hemoglobinuria (PCH), an autoimmune hemolytic anemia. In the past, PCH was most commonly associated with syphilitic infections; however, now it is more frequently identified as a sequela in pediatric patients with upper respiratory infections. The authors present a case of a 5-year-old female who presented with hemolytic anemia and was subsequently diagnosed with PCH.

Development and Detection of Kidd Antibodies

Kidd antibodies have a reputation for causing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We present a case of an untransfused male patient who developed anti-Kidd(a) (Jk(a)) antibodies after receiving an allogenic renal transplant. The formation of this antibody was associated with exposure to the Kidd antigen expressed on the tubular epithelium of the transplanted kidney. The 59-year-old white male patient had received a cadaveric renal transplant at our clinic and returned 5 years later with proteinuria and elevated serum creatinine levels, consistent with nephrotic syndrome. We review the expression of Kidd antigens and the development and detection of Kidd antibodies, and discuss the case reports from the literature of Kidd antibodies associated with kidney-graft rejection that suggest Kidd antigens play a role as a minor histocompatibility antigen.

Therapeutic Apheresis in Critically Ill Patients

Therapeutic apheresis procedures in critically ill patients comprises of therapeutic plasma exchange in most cases but also less commonly, erythrocytapheresis (red cell exchange), thrombocytapheresis, or leukocytapheresis. These procedures present a number of challenges to the apheresis healthcare team, and there are myriad beneficial and adverse effects for patients. In this patient population, one has to weigh the risks against the benefits and especially in those situations where apheresis is requested as a treatment when other alternative therapies have failed. Therapeutic plasma exchange is capable of removing toxins, pathologic auto‐ and allo‐antibodies but will also remove beneficial medications, clotting factors and cations which are chelated by citrate anticoagulant. Herein, we review clinically significant issues that are commonly encountered in patients that are in the intensive care unit and have conditions that require therapeutic apheresis. J. Clin. Apheresis 2011.

Iron Deficiency Anemia in Patients Undergoing Extracorporeal Photopheresis for Cutaneous T-Cell Lymphoma

Objective To describe the indicidence and severity of iron deficiency anemia (IDA) in patients who have received extracorporeal photopheresis (ECP) treatment of cutaneous T-cell lymphoma (CTCL). Methods We performed a retrospective study during a 9-year period of patients with CTCL who were treated with ECP. ECP was performed with UVAR XTS and CELLEX (Therakos Inc). IDA was defined by a drop in hemoglobin (Hb), mean cell volume (MCV), and increased red blood cell distribution width (RDW). Results We identified a total of 36 patients; 1 patient was excluded due to severe anemia. In 35 patients, initial hemoglobin values ranged from 9.8 g per dL to 15.9 g per dL, and patients received 4 to 327 ECP treatments. In all, 28 patients showed decreases in Hb of 0.8 g per dL to 6 g per dL during treatments. Conclusion Chronic ECP led to IDA in 28 of 35 patients with CTCL. IDA occurs due to blood loss when ECP equipment does not return full blood volume to patients.

Product Investigations: A Streamlined Electronic Process

Due to the volume of product investigations submitted to our institution, a consistent system of monitoring and follow-up on postdonation information of transfused blood products was developed. The original manual paper-laden system needed to be revised and upgraded to an electronic system that captured all communication among the blood supplier, the transfusing institution, the physician, …