ABSTRACT
Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood stem cells administered after very low dose total body irradiation (TBI) (100cGy). The donor cells were anticipated to be rejected, so no graft-versus-host (GVHD) prophylaxis was used. Patients with persistent disease beyond 8 weeks could be further treated with infusions of irradiated haploidentical donor cells. Of the 10 patients enrolled in the study, durable engraftment of allogeneic cells was seen in one patient. Two patients with resistant relapsed acute myelogenous leukemia (AML) had a disease response. Analysis of T cell reactivity from one patient who achieved a complete response but did not have durable engraftment of donor cells indicated that disease response was associated with the generation of host-derived anti-leukemic cytotoxic CD8+ T cells that reacted with an AML-associated proteinase 3 epitope. Results from this patient suggest that allogeneic therapy induced a host anti-tumor response associated with cytotoxic T cells reactive with a low affinity self-antigen.
Subject(s)
Hematologic Neoplasms/surgery , Aged , Aged, 80 and over , Antigens, CD/blood , Antigens, CD34/blood , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CD3 Complex/blood , CD8-Positive T-Lymphocytes/immunology , Cell Transplantation , Female , Flow Cytometry , Hematologic Neoplasms/immunology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/surgery , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/surgery , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/surgery , Male , Middle Aged , Pilot Projects , Tissue Donors , Tissue Expansion/methods , Tissue and Organ Harvesting/methods , Transplantation, HomologousABSTRACT
PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.
Subject(s)
Carcinoma, Renal Cell/therapy , Cell Transplantation , Kidney Neoplasms/therapy , Killer Cells, Natural/immunology , T-Lymphocytes/immunology , Adult , Aged , Female , HLA Antigens , Humans , Killer Cells, Natural/radiation effects , Male , Middle Aged , T-Lymphocytes/radiation effectsABSTRACT
This article reviews transfusion risks with particular emphasis on the critically ill. It describes the various types of noninfectious,infectious, and mild-to-severe reactions that can occur in a trans-fused patient. The article describes differential diagnosis of these reactions and the handling and treatment of the patient. Diagnosis of the type of transfusion reaction by laboratory tests is detailed. Finally, the article discusses the dangers of human error with possible strategies to combat this problem using new technologies.
Subject(s)
Critical Care , Critical Illness , Transfusion Reaction , Humans , RiskABSTRACT
CONTEXT: Platelet transfusions are used in clinical practice as prophylaxis or to treat bleeding thrombocytopenic patients. This procedure also carries risks and costs and must be allocated appropriately. OBJECTIVE: To evaluate physician compliance with the platelet transfusion criteria in our tertiary care academic institution. DESIGN: We evaluated platelet unit releases from the transfusion service for 4 months, and we retrieved pretransfusion platelet counts. Reasons for transfusion were obtained by reviewing patient charts and talking to clinicians. Compliance with hospital criteria for platelet use was determined. RESULTS: Platelets were given to 113 patients in 282 transfusion episodes. Criteria were not met for 32 (11%) of 282 platelet transfusions. Justifiable reasons for transfusion at platelet counts of greater than 10 x 10(3)/microL included bleeding risk from oral ulcers, other risks of bleeding in patients who were transfused before discharge, and antiplatelet drug use in cardiac surgery patients. Reasons for transfusion at platelet counts greater than 10 x 10(3)/ microL that were not justified include transfusion at a platelet count of 110 x 10(3)/microL to a lung cancer patient with no platelet dysfunction and transfusion to 4 septic patients with platelet counts of 70 to 90 x 10(3)/microL. CONCLUSIONS: This study showed 89% physician compliance with hospital platelet transfusion criteria. Transfusion-medicine specialists concurred that strict adherence to hospital blood usage criteria was not applicable for 9.2% of these patients; however, 5 (1.8%) of 282 platelet transfusions were not indicated and could have been prevented by transfusion medicine physician intervention.
Subject(s)
Guideline Adherence , Platelet Transfusion , Practice Guidelines as Topic , Guideline Adherence/statistics & numerical data , Hospitals, Teaching/statistics & numerical data , Humans , Platelet Count , Retrospective Studies , Unnecessary Procedures/statistics & numerical dataABSTRACT
The paper by Fung YL and Williams BA describes TRALI in leukemic children in order to raise awareness of the need to include this in the differential diagnosis of acute respiratory distress. Detection of TRALI in children with other co-morbidities is difficult. Well-documented cases of TRALI in children are few due to the lack of recognition and difficulty in identifying the antibodies since these may not be always present. Hematology/oncology patients who are chronically transfused and are allo-immunized are at greater risk than the general pediatric population. Thus an awareness of this reaction to blood transfusion helps facilitate prompt treatment and preventive measures.
Subject(s)
Leukemia, Myeloid, Acute/complications , Leukemia, Promyelocytic, Acute/complications , Platelet Transfusion/adverse effects , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Adolescent , Anti-Inflammatory Agents/administration & dosage , Blood Donors , Child, Preschool , Diagnosis, Differential , Female , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Promyelocytic, Acute/therapy , Male , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Risk FactorsABSTRACT
This article discusses the impact of anemia in the context of the perioperative setting. Relevant data from animal and human studies, the adaptive mechanisms in anemia, and current views on transfusion triggers are evaluated. Recommendations are provided for the anesthesiologist for transfusion of red blood cells.
Subject(s)
Anemia/therapy , Blood Transfusion , Anemia/physiopathology , HumansABSTRACT
Cryoglobulins are immunoglobulins that have tendency to precipitate in temperatures below 37 degrees C and dissolve with rewarming. Monoclonal cryoglobulins are usually associated with a distinct hematological disorder and often are asymptomatic. Heat insoluble cryoglobulin has been described with Sjogren's syndrome and glomerulonephritis but, not with multiple myeloma. Severe sensitivity to cold occurs with high thermal insolubility of the cryoprotein, with dramatic symptoms when exposed to minimal lowering of the temperature. We report a case of a 49 year old man with multiple myeloma and an unusual type I cryoglobulin that caused occlusive gangrene. The cryoglobulin appeared as a milky white precipitate that was resistant to re-suspension and did not dissolve at 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which dissolved at 56 degrees C, showed it to be composed of a monoclonal IgG kappa protein (3.5 g/dl). Unlike most high thermal insoluble cryoglobulin, cold associated symptoms were not seen. In addition to steroids, plasmapheresis was initiated thrice a week with albumin fluid replacement. Plasmapheresis caused a marked decline in cryocrit levels from 21% to less than 0.5% in 9 days after 4 procedures with resolution of the gangrene of the feet and after 6 treatments, vasculitic symptoms improved dramatically. The cryoglobulin test was negative 2 weeks after initiation of treatment. The patient was treated for the myeloma and there was no recurrence of occlusive symptoms. Proper laboratory procedure and careful examination and handling of cryoglobulinemic samples facilitate detection of unusual cryoglobulins. This is a unique report of multiple myeloma with gangrene of lower extremities that has a heat insoluble cryoglobulin.
Subject(s)
Cryoglobulinemia/complications , Cryoglobulinemia/immunology , Cryoglobulins/isolation & purification , Gangrene/complications , Gangrene/immunology , Multiple Myeloma/complications , Multiple Myeloma/immunology , Cryoglobulinemia/therapy , Gangrene/therapy , Hot Temperature , Humans , Male , Middle Aged , Multiple Myeloma/therapy , Plasmapheresis , SolubilityABSTRACT
BACKGROUND: ABO autoantibodies are rare. Most reported examples have been antibodies with 4 degrees C titers not greater than 256 in patients without apparent hemolytic anemia. Most high-titer, high-thermal-amplitude, complement-activating cold agglutinins are associated with hemolytic anemia. STUDY DESIGN AND METHODS: A 52-year-old man presented with acrocyanosis and mild small-vessel brain disease, but no evidence of obvious hemolytic anemia. Regular plasmapheresis treatment was helpful in relieving the clinical symptoms associated with acrocyanosis. Serologic methods were used to study the patient's RBCs and sera. RESULTS: The patient's RBCs were strongly reactive with anti-C3 and anti-IgM and weakly reactive with anti-IgA. The patient's serum contained a high-titer, high-thermal-amplitude, IgMkappa autoanti-B, capable of activating complement in vitro. CONCLUSION: A patient with a powerful ABO autoantibody is described. This patient had acrocyanosis but did not appear to have an obvious hemolytic anemia. This case is a good example of the lack of correlation between in vitro serologic tests and in vivo reactions in individual patients.