The Clinical Pictures of Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening.

Hemolytic anemia due to warm autoantibodies.

The diagnosis of autoimmune hemolytic anemia (AHA) requires evidence of shortened red blood cell (RBC) survival mediated by autoantibodies directed against autologous RBCs. About 80 percent of patients with AHA have warm-reactive antibodies of the IgG isotype; the remainder exhibit cold-reactive autoantibodies. Typical patients exhibit anemia, reticulocytosis, spherocytes and polychromasia on the blood film and a positive direct antiglobulin test (DAT).

Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation.

Pilocarpine hydrochloride has been reported to increase salivation and decrease oral mucositis in patients receiving head and neck radiotherapy, but there is only one report of its use in a cancer chemotherapy patient population. This prospective, double-blinded, randomized, placebo-controlled trial was undertaken to determine the efficacy of pilocarpine for the moderation of oral mucositis during autologous blood stem cell transplantation. Subjects were randomized to receive a 5 mg tablet of pilocarpine, or a placebo, during and following chemotherapy.

Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex.

Unmanipulated autologous bone marrow transplant (ABMT) offers patients with chronic myelogenous leukemia (CML) a long-term survival of 10%, at best. Immunotherapy has a role in the myeloid leukemias, and there is increasing evidence that of all hematopoietic neoplasms, CML may be the most susceptible to immune regulation. Roquinimex is known to enhance T cell, NK cell and macrophage activity.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

Purpose: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy.

Patients And Methods: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea.

Continuous infusion cyclosporine and nifedipine to day +100 with short methotrexate and steroids as GVHD prophylaxis in unrelated donor transplants.

Unrelated donor marrow transplantation is associated with an increased incidence of graft-versus-host disease (GVHD) compared with sibling donor transplants. Forty-one patients undergoing unrelated donor transplants were treated with a GVHD prophylaxis regimen that consisted of continuous infusion cyclosporine from day -1 to 100 days post transplant along with nifedipine, glucocorticoids and short-course methotrexate. The regimen was well-tolerated in this cohort with mostly high risk disease.

Autotransplantation for relapsed or refractory Hodgkin's disease: long-term follow-up and analysis of prognostic factors.

Seventy consecutive patients with refractory or relapsed Hodgkin's disease who received high-dose chemotherapy followed by autologous stem cell rescue were analyzed to identify clinically relevant predictors of long-term event-free survival. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine and cyclophosphamide (BEAC). The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 32% (95% confidence interval; 18-45%) with a median follow-up of 3.

Pathogenesis and management of paroxysmal nocturnal haemoglobinuria.

Over the past 30 years, our understanding of the pathogenesis of paroxysmal nocturnal haemoglobinuria (PNH) has increased dramatically. During that time, the events during complement activation and regulation have been described, the molecular basis for the exaggerated complement sensitivity of PNH cells has been uncovered, and the responsible gene mutation has been identified. It is now possible to relate almost all the protean manifestations of PNH to a single gene mutation in a haematopoietic stem cell.

Treatment of multifocal lymphoma of bone with intensified ProMACE-CytaBOM chemotherapy and involved field radiotherapy.

Primary bone involvement is an unusual extranodal presentation of non-Hodgkin lymphoma (NHL). The optimal treatment for this entity has not been determined. While solitary bone lymphomas can be eradicated with local radiation in 50% of patients, distant relapses occur frequently, and the treatment of patients with multifocal osseous disease, or those presenting with associated soft tissue invasion or adenopathy is even less satisfactory.

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin's lymphoma (NHL) were evaluated to assess long-term event-free survival and to identify important prognostic factors. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 34% (95% confidence interval: 24-44%) with a median follow-up of approximately 3 years (range 0-7.

Treatment of the neutropenia of Felty syndrome.

This review sets out to synthesize and critically evaluate the current reported data regarding therapeutic options for the neutropenia associated with Felty syndrome (Felty neutropenia). A MEDLINE search and bibliographies from recent reviews were used to identify trials and case reports that provided sufficient data to evaluate the effect of various interventions on both the neutropenia and the clinical course of patients with Felty syndrome. Data were obtained on baseline hematologic profiles, bone-marrow biopsies, and patient characteristics; length of follow-up; hematologic and clinical responses to the various interventions; and side-effect profiles.

Changes in cytoskeletal actin content, F-actin distribution, and surface morphology during HL-60 cell volume regulation.

Cell volume regulation occurs via the regulated fluxes of ions and solutes across the cell membrane in response to cell volume perturbations under anisotonic conditions. Our earlier studies in human promyelocytic leukemic HL-60 cells showed that volume-dependent changes in total cellular F-actin content occur concomitantly as an inverse function of acute cell volume changes in anisotonic media (Hallows et al., 1991, Am.

The effect of dexamethasone on functional properties of HL60 cells during all-trans retinoic acid induced differentiation. Are there implications for the retinoic acid syndrome?

Differentiation therapy for acute promyelocytic leukemia (APL) using all-trans-retinoic acid (ATRA) has improved the prognosis of the disease. ATRA therapy also causes a newly recognized clinical syndrome, the "retinoic acid syndrome" (RAS), which can be successfully managed with dexamethasone. Because aberrant function of maturing leukemic granulocytes may cause this syndrome, and because dexamethasone is useful clinically, we studied functional properties of maturing HL60 cells cultured in the presence and absence of dexamethasone.

Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.

All-trans retinoic acid (ATRA) is a differentiating agent that has been successfully used in the treatment of patients with acute promyelocytic leukemia (APL). Functional properties of peripheral blood neutrophils from a patient with APL during treatment with ATRA have been studied. Wright stain of patient neutrophils showed hypogranulation and loose nuclear chromatin when compared with normal neutrophils.

Patients > or = age 40 years undergoing autologous or allogeneic BMT have regimen-related mortality rates and event-free survivals comparable to patients < age 40 years.

To evaluate the safety and efficacy of marrow transplantation for older adults, the regimen-related mortality and event-free survival for patients > or = 40 years were compared with those for patients < 40 years. Of 148 consecutive patients receiving autotransplants for lymphoma or Hodgkin's disease, 70 were < 40 years and 78 were > or = 40 years at the time of transplant, including 40 who were > or = 50 years and 12 who were > or = 60 years. Eleven patients (16%) in the younger age group died from transplant-related complications compared with 4 (5%) in the older age group.

Functional properties of HL60 cells matured with all-trans-retinoic acid and DMSO: differences in response to interleukin-8 and fMLP.

All-trans-retinoic acid (ATRA) causes granulocyte differentiation in patients with acute promyelocytic leukemia. HL60 cells are frequently used as an in vitro model for studying granulocytes during maturation. We have previously studied actin polymerization in response to fMLP in HL60 cells undergoing DMSO induced maturation, and reported that IL-8 causes actin polymerization in neutrophils in a manner similar to fMLP.

The Rochester practice-based experience. An experiment in medical education.

Background: Recent changes in the organization and financing of medical practice have resulted in a shift of patient care from the hospital to ambulatory locations and dramatically changed the mix and severity of the inpatient population. Medical educators are concerned that hospitalized patients are not truly representative of the practice of internal medicine and may be unsuitable for the education of third-year medical students. The University of Rochester (NY) Department of Medicine recently established a "practice-based" component to complement the inpatient segment of the third-year medicine clerkship.

Engagement of the T-cell antigen receptor by anti-CD3 monoclonal antibody causes a rapid increase in lymphocyte F-actin.

Activation of protein kinase C (PKC) causes a rapid and sustained increase in the F-actin of T lymphocytes. Because the phosphatidylinositol pathway and the cytoskeleton play a role in lymphocyte activation, we examined the relationship between signal transduction and the F-actin increase in human blood T cells. Anti-CD3 monoclonal antibodies (mAbs) initiate signals which result in activation of T lymphocytes through the T-cell receptor (TCR), involving the phosphatidylinositol pathway, activation of PKC, and increasing intracellular calcium (Cai2+).