Aplasia In Patients Research Articles

Pure red cell aplasia in patients treated with recombinant erythropoietin for anemia due to chronic renal disease

Pure red cell aplasia in patients treated with recombinant erythropoietin for anemia due to chronic renal disease

Epoetin-associated pure red cell aplasia in patients with chronic kidney disease: solving the mystery

Epoetin-associated pure red cell aplasia in patients with chronic kidney disease: solving the mystery

Parvovirus B-19 induced acute pure red cell aplasia in patients with chronic lymphocytic leukemia and neurofibromatosis type-1

Parvovirus B19 induced pure red cell aplasia (PRCA) has been previously reported in a variety of settings. We present two cases, an adult patient with chronic lymphocytic leukemia (CLL) and a child with neurofibromatosis type-1 (NF-1), where the abrupt appearance of severe anemia raised ominous clinical suspicions. Evidence of recent parvovirus B19 infection in association with the selective erythroid precursor deficiency in marrow helped exclude other etiologies.We emphasize the importance of bearing this infectious agent in mind, even when there are associated disorders (such as CLL) that may independently cause PRCA. An association of NF-1 with acute PRCA has not been described in indexed English literature in the past.

Evaluation of Angiogenesis and Vascular Endothelial Growth Factor Expression in the Bone Marrow of Patients with Aplastic Anemia

It is generally appreciated that bone marrow function and growth of myelopoietic cells depends on an intact microvasculature. A pivotal regulator of angiogenesis is vascular endothelial growth factor (VEGF). Here, we describe analysis of VEGF expression and microvessel density in the bone marrow of patients with aplastic anemia by immunohistochemistry. Bone marrow was examined at diagnosis and at the time of hematological remission after immunosuppressive therapy using anti-thymocyte globulin, cyclosporin A, and glucocorticoids or allogeneic stem cell transplantation. At diagnosis, both VEGF expression and microvessel density were found to be significantly lower in aplastic anemia compared to normal bone marrow (aplastic anemia, 1.1 +/- 0.7 events per field, versus controls, 5.9 +/- 3.0 events per field; P < 0.05). In response to successful therapy, VEGF and microvessel density in the bone marrow increased substantially. Serum VEGF levels were also found to be significantly lower at diagnosis in aplastic anemia compared to healthy controls (aplastic anemia, 51 +/- 35 pg/ml versus controls, 444 +/- 220 pg/ml; P < 0.05). VEGF in the serum increased substantially after successful immunosuppressive therapy or stem cell transplantation (P < 0.05). Taken together, these data show that aplastic anemia is associated with reduced angiogenesis and reduced VEGF expression.

Epoetin-associated pure red cell aplasia in patients with chronic kidney disease: solving the mystery

A substantial increase in the incidence of pure red cell aplasia (PRCA) associated with recombinant human erythropoietin (epoetin) treatment occurred in 1998. The upsurge of antibody-mediated PRCA was almost exclusively associated with chronic kidney disease patients who received subcutaneous epoetin therapy and the formulation of epoetin-alpha distributed outside the USA (EPREX/ERYPO). A systematic programme of technical, immunological and epidemiological investigations was initiated to identify the possible causes. The potential causes were evaluated on the basis of the following criteria: temporal correlation with the increase in incidence of PRCA, significant difference between EPREX/ERYPO and other epoetin products, sufficient concentration in the product to elicit a weak immune response, evidence of immunogenic activity in animals supportive, and consistent with available clinical data. Organic compounds that were leached from rubber stoppers through the action of polysorbate 80 were detected in pre-filled syringes with uncoated rubber stoppers containing polysorbate 80-formulated EPREX/ERYPO (introduced outside the USA in 1998). The leachates were not present when the stoppers were coated, in the product formulated with human serum albumin or in other epoetin products. The adjuvant activity of the leachates was demonstrated in mice. The incidence of PRCA was significantly higher in patients exposed to the polysorbate 80 formulation of epoetin-alpha delivered from pre-filled syringes with uncoated rubber stoppers, which were recalled in 2003, than in patients exposed to the same formulation from syringes with coated rubber stoppers. In conclusion, these data strongly suggest that leachates were the critical contributory factor in the increased incidence of antibody-mediated PRCA attributed to EPREX/ERYPO.

Creation of a neovagina according to Wharton-Sheares-George in patients with Mayer-Rokitansky-Küster-Hauser syndrome

To introduce a simple and quick surgical alternative for creating a neovagina in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome that offers good anatomic and functional results. Historical report. Tertiary center for gynecologic endocrinology. Three patients with MRKH syndrome. The creation of a neovagina according to Wharton-Sheares-George in patients with MRKH syndrome. Axis, length, and width of neovagina. The George modification of the Wharton-Sheares neovaginoplasty was successfully performed in three patients. The results were excellent (normal axis and adequate length and width of neovagina), and there were no major complications. The George modification of the Sheares technique represents a simple, safe, and effective surgical option for creating a neovagina. The procedure is not highly complex and is therefore easy to learn and perform; no special surgical equipment is needed. Anatomic and functional results are very satisfying. Short-term hospitalization, accelerated recovery, and a rapid return to everyday life are important benefits for these young patients. These benefits also result in lower surgery-related expenses and therefore reduce the strain on the hospital's budget compared with other therapeutic options. The creation of a neovagina according to Wharton-Sheares-George might provide a satisfactory alternative for the surgical management of vaginal aplasia in patients with MRKH syndrome.

Effect of switching from subcutaneous to intravenous administration of epoetin-α in haemodialysis patients: Results from a Swedish multicentre survey

In 2002, many haemodialysis patients were switched from subcutaneous (s.c.) to intravenous (i.v.) administration of epoetin-alpha following reports of antibody formation and development of pure red-cell aplasia in patients treated via the s.c. route. We evaluated the possible effect of this change in the route of administration on haemoglobin (Hb) levels and epoetin-alpha requirements. This retrospective survey involved 223 haemodialysis patients from 25 Swedish centres. Variables were recorded before and after a mean period of 213 days (range 89-297 days) after the change in the route of administration. The mean epoetin-alpha do had to be increased from 159+/-104 to 185+/-122 U/kg/week (p<0.0001) to maintain a constant Hb level (121+/-12 vs 120+/-11 g/l). Plasma ferritin, albumin, C-reactive protein, iron, iron transferrin saturation and body mass index remained constant. The relative increase in epoetin-alpha dose was negatively correlated with the s.c. dose prior to the switch (R=-0.3; p<0.0001), with the most pronounced dose increases occurring in patients who received a low s.c. dose. A switch from s.c. to i.v. administration of epoetin-alpha in haemodialysis patients was accompanied by an increase in the mean dose requirement of 15%. This increase may be less pronounced in patients receiving high s.c. doses prior to the switch.

Rapid Risk-Profiling Including Fast Donor Search within a Multi-Center Trial Allows for Early Allogeneic Stem Cell Transplantation during Aplasia in Patients with High-Risk Acute Myeloid Leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing allogeneic HSCT within induction therapy can circumvent these problems and may furthermore reduce cumulative toxicity in high risk patients.Therefore, the prospective randomized treatment trial AML2003 for patients <= 60 years was set up, to investigate the feasibility and value of an intensified treatment strategy, i.e. early allogeneic stem cell transplantation in aplasia after induction therapy, for high risk AML patients in a multi-center setting. To achieve this goal, rapid analysis of cytogenetics, FLT3 status and HLA-types of the patient and possible family donors is of utmost importance. This fast search diagnostics together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. Furthermore, in all patients the likelihood to find an unrelated donor is checked by an internet search in the BMDW database.Within the first 8 months 107 AML patients with a median age of 48 (17–60) years were included in the study. Fast search diagnostics was complete within a median of 15 (range 5–31) days after arrival of the bone marrow samples for all patients. 57/107 patients were randomized into the intensified treatment arms. Out of these 25 (44%) patients with high risk characteristics have been identified. A suitable related or unrelated donor was found for 22 (88%) of those high-risk patients. Nine of those high risk patients with a donor (41%) received early allogeneic stem cell transplantation in aplasia after the first (n=4) or the second (n=5) induction therapy course on an intend to treat basis within the protocol. Three were transplanted with stem cells of related and six of unrelated donors. The preparative regimen consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. So far no treatment associated death had to be recognized.These encouraging preliminary results show that fast risk-profiling and early donor-search is feasible in a large multi-center study. This leads to a significant proportion of early allogeneic stem cell transplants in aplasia after induction therapy within the group of high risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation.

Hemostatic events in patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) increase the morbidity and mortality in this cohort. Little is known about the impact of graft-versus-host disease (GvHD) or of thrombophilic gene mutations/polymorphisms on these complications. Eighty-nine allogeneic stem-cell recipients and their donors were evaluated prospectively for the presence of the factor V G1691A mutation, the prothrombin G20210A mutation, the 5,10-methylenetetrahydrofolate-reductase (MTHFR) C677T mutation, the glycoprotein IIIa PI(a1/a2) polymorphism, the fibrinogen-beta-chain 455G/A polymorphism, the plasminogen activator inhibitor-1 -675 4G/5G polymorphism, and the angiotensin-converting enzyme intron 16 I/D polymorphism. These mutations/polymorphisms and GvHD parameters were correlated to hemostatic and toxic complications after transplantation. The data were compared with those of 128 healthy controls. The PAI-1 4G/4G polymorphism increases the risk for catheter thrombosis after HSCT 5.7-fold (32.2% vs. 71.4%, P<0.05). In patients with hepatic veno-occlusive disease, the frequency of the PAI-1 4G allele is also increased (83.3% vs. 55.1%, NS). Thrombophilic mutations/polymorphisms in donors do not influence complications in the corresponding recipients. The MTHFR TT genotype does not modify severity and duration of mucositis and aplasia in patients receiving methotrexate prophylaxis. Patients with chronic GvHD have a higher risk of thromboembolism (12.9% vs. 1.7%, P<0.05). Thrombophilic gene mutations have only a moderate influence on hemostatic complications in patients undergoing HSCT. This may be because of the overwhelming immunologic impact of GvHD on hemostasis in the allogeneic transplantation setting.

Antibiothérapie ambulatoire chez les enfants neutropéniques fébriles: Analyse de la littérature

NEW STRATEGIES: Fever in a neutropenic patient requires the rapid initiation of a broad spectrum antibiotic and continued until correction of the neutropenia. Several studies have been conducted recently in order to define the populations of children in whom the antibiotherapy could be suspended early without risk of relapse of fever and/or severe infection. Moreover, the high costs of hospitalisation and the limited number of beds in the departments of Paediatric Oncology Haematology have led to studies on the feasibility of an antibiotherapy at home. THE EARLY SUSPENSION OF THE ANTIBIOTHERAPY: The criteria retained in several studies for the early suspension of the antibiotherapy have been: apyrexia for at least 24 hours, a satisfactory clinical status, the absence of positive haemocultures and haematological signs showing the end of aplasia in patients in remission of their disease. Studies have confirmed the possibility of early suspension of intravenous antibiotics in low-risk patients, without fever and without microbiological signs. THE PLACE OF ORAL ANTIBIOTICS: In several comparative studies, the success rate with intravenous antibiotics and oral antibiotics was comparable. The rate of failures was greater in patients with severe initial neutropenia. OUTPATIENT ANTIBIOTICS: In children, 2 types of studies have been conducted. The first studied the feasibility of an antibiotherapy at home following antibiotherapy in the hospital in order to reduce the costs and duration of hospitalisation. The others proposed an antibiotherapy at home from the start, either with the intravenous or the oral route. Following all these studies, it appeared that, in certain low-risk neutropenic children with fever, not only the antibiotics could be suspended before the complete correction of the neutropenia, but also a large spectrum oral antibiotherapy could replace the intravenous antibiotherapy and outpatient treatment would therefore be feasible.

Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation

We conducted 2 sequential studies of donor leukocyte infusion (DLI) in 26 patients with chronic myeloid leukemia in hematologic relapse after unmodified allogeneic bone marrow transplantation. In the first study, cells for DLI were collected from 13 donors who were not treated with granulocyte colony-stimulating factor (G-CSF) (group 1). In the second study, cells were collected from 13 donors who received G-CSF before apheresis (group 2) in an attempt to avoid aplasia after DLI. Patients in group 2 received 550-fold more CD34+ cells than those in group 1. We found no significant difference in the incidence (31% versus 22%), onset time (41 vs. 48 days), or duration (15 vs. 14 days) of cytopenia after DLI in the 2 groups. G-CSF given to donors before collection of cells did not prevent aplasia. These findings support the hypothesis that the pathogenesis of aplasia after DLI is not restricted to the destruction of recipient hematopoietic cells but also involves failure of donor hematopoiesis by undefined mechanisms. Biol Blood Marrow Transplant 2000;6(3A):321-6.

Viral inactivation of fresh frozen plasma.

Viral inactivation of fresh frozen plasma.

The use of monoclonal antibody R92F6 and polymerase chain reaction to confirm the presence of parvovirus B19 in bone marrow specimens of patients with acquired immunodeficiency syndrome.

Abstract Background.—Parvovirus B19 infection is a cause of chronic anemia and red cell aplasia in patients with acquired immunodeficiency syndrome (AIDS) and in other immunocompromised hosts. Anemia in AIDS patients has a multifactorial etiology, with parvovirus B19 infection being an infrequent but nevertheless treatable cause. Therapy with intravenous immune globulin can result in rapid improvement of parvovirus-induced anemia. This treatment is expensive, therefore accurate and rapid confirmation of parvovirus infection is important in providing appropriate and cost-effective therapy. Methods.—Bone marrow samples from 2 AIDS patients with severe anemia and reticulocytopenia were studied. Bone marrow morphology and serologic studies were evaluated for parvovirus B19 infection. An immunohistochemical method using a monoclonal antibody, R92F6, to B19 capsid proteins was utilized on decalcified, B5-fixed, paraffin-embedded bone marrow biopsies. Bone marrow aspirate cells were examined by electron microsco...

Cyclosporin therapy for pure red cell aplasia in patients with chronic lymphocytlc leukemia

Cyclosporin therapy for pure red cell aplasia in patients with chronic lymphocytlc leukemia

Human Parvovirus B19-Induced Epidemic Acute Red Cell Aplasia in Patients With Hereditary Hemolytic Anemia

From March to August 1984, 26 patients with hereditary hemolytic anemia in northeastern Ohio developed acute, profound red cell aplasia. The patients included 14 males and 12 females 2 to 23 years old, with sickle cell anemia (20 cases), hemoglobin SC-disease (4 cases), sickle-beta-thalassemia (1 case), or hereditary spherocytosis (1 case). All had an acute onset of severe reticulocytopenia and anemia and prodromal symptoms of illness including fever, abdominal symptoms, headache, and arthralgias. Twenty-two received transfusions. Reticulocytosis occurred spontaneously within 2 to 14 days of presentation. In five acute-phase sera, 10(8) to 10(12) viral particles/mL were detected by electron microscopy. Human parvovirus B19 DNA was demonstrated in high concentration by hybridization in the same five acute-phase sera and in low concentration in sera of eight additional patients. The five highly viremic sera inhibited erythroid colony formation in vitro. B19-specific IgM was detected in sera of 24/26 patients, and B19-specific IgG in 21 of 22 patients tested. Our results indicate that human parvovirus B19 was the etiologic agent in this large epidemic of life-threatening acute red cell aplasia in patients with hereditary hemolytic anemia.

Human parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia

From March to August 1984, 26 patients with hereditary hemolytic anemia in northeastern Ohio developed acute, profound red cell aplasia. The patients included 14 males and 12 females 2 to 23 years old, with sickle cell anemia (20 cases), hemoglobin SC-disease (4 cases), sickle- beta-thalassemia (1 case), or hereditary spherocytosis (1 case). All had an acute onset of severe reticulocytopenia and anemia and prodromal symptoms of illness including fever, abdominal symptoms, headache, and arthralgias. Twenty-two received transfusions. Reticulocytosis occurred spontaneously within 2 to 14 days of presentation. In five acute-phase sera, 10(8) to 10(12) viral particles/mL were detected by electron microscopy. Human parvovirus B19 DNA was demonstrated in high concentration by hybridization in the same five acute-phase sera and in low concentration in sera of eight additional patients. The five highly viremic sera inhibited erythroid colony formation in vitro. B19- specific IgM was detected in sera of 24/26 patients, and B19-specific IgG in 21 of 22 patients tested. Our results indicate that human parvovirus B19 was the etiologic agent in this large epidemic of life- threatening acute red cell aplasia in patients with hereditary hemolytic anemia.

Diaziquone Given as a Continuous Infusion Is an Active Agent for Relapsed Adult Acute Nonlymphocytic Leukemia

Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.

Diaziquone given as a continuous infusion is an active agent for relapsed adult acute nonlymphocytic leukemia

Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.

Autologous cryopreserved platelets and prophylaxis of bleeding in autologous bone marrow transplantation.

Autologous platelets were harvested and cryopreserved in eight consecutive patients elected for ablative chemotherapy and autologous bone marrow transplantation (ABMT) for solid malignancy. There was a 19% loss in platelet count after the freeze thaw and wash procedure; with an in vitro functional loss of 40-60%. No correlation could be found for individual platelet transfusions between in vitro functional tests and in vivo recovery. Six consecutive patients received a total of 16 autologous platelet transfusions in the aplastic phase of ABMT. No bleeding was observed during the study period and there was no CMV infection in the recipients. While improvement in freezing and subsequent handling is desirable, autologous cryopreserved platelets can safely be used for the prophylaxis of bleeding during aplasia in patients treated with ABMT.

Die Aplasie der perisylvischen Region

The article reports on 11 cases of opercular aplasia in patients aged 5 to 44 years. Aplasia occurred to a greater extent in the frontal operculum than in the temporal operculum, and was always associated with space-requiring arachnoidal cysts. Symphyses and obstruction of the flow of the basal CSF spaces were also seen. In 91% of the cases, the aplasia was localized on the left side, 91% of the patients were males. The patients tend to decompensate after a cerebrocranial trauma, and in many cases surgery reveals a subdural haematoma which fills the aplastic region, due to detachment of the exposed cerebral veins effecting basal drainage. In the remaining cases, surgery was performed because of general signs of cerebral compression, exacerbation of an existing disease associated with attacks, or because of the space-occupying character of the concomitant arachnoidal cysts. In patients with opercular aplasia without space-occupying arachnoidal cysts, surgery is not performed for the time being; instead, regular neurological and CT control is effected.