Showing papers on "Cytopenia published in 2011"

Immunosuppressive Therapy for Patients With Myelodysplastic Syndrome: A Prospective Randomized Multicenter Phase III Trial Comparing Antithymocyte Globulin Plus Cyclosporine With Best Supportive Care—SAKK 33/99

Abstract: Purpose Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in patients with immune-mediated marrow failure. Patients and Methods This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration. Results Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years...

Pancytopenia: a clinico hematological study.

Abstract: Background: Pancytopenia is a relatively common hematological entity. It is a striking feature of many serious and life-threatening illnesses, ranging from simple drug-induced bone marrow hypoplasia, megaloblastic anemia to fatal bone marrow aplasias and leukemias. The severity of pancytopenia and the underlying pathology determine the management and prognosis. Thus, identification of the correct cause will help in implementing appropriate therapy. Objectives: To study the clinical presentations in pancytopenia due to various causes; and to evaluate hematological parameters, including bone marrow aspiration. Materials and Methods: It was a prospective study, and 104 pancytopenic patients were evaluated clinically, along with hematological parameters and bone marrow aspiration in Hematology Unit, Department of Pathology, JJMMC, Davanagere, during the period of September 2005 to September 2007. Results: Among 104 cases studied, age of patients ranged from 2 to 80 years with a mean age of 41 years, and male predominance. Most of the patients presented with generalized weakness and fever. The commonest physical finding was pallor, followed by splenomegaly and hepatomegaly. Dimorphic anemia was the predominant blood picture. Bone marrow aspiration was conclusive in all cases. The commonest marrow finding was hypercellularity with megaloblastic erythropoiesis. The commonest cause for pancytopenia was megaloblastic anemia (74.04%), followed by aplastic anemia (18.26%). Conclusion: The present study concludes that detailed primary hematological investigations along with bone marrow aspiration in cytopenic patients are helpful for understanding disease process and to diagnose or to rule out the causes of cytopenia. These are also helpful in planning further investigations and management.

Congenital Amegakaryocytic Thrombocytopenia: Clinical Presentation, Diagnosis, and Treatment

Abstract: Congenital amegakaryocytic thrombocytopenia (CAMT, MIM #604498) is a rare inherited bone marrow failure syndrome presenting as isolated hypomegakaryocytic thrombocytopenia at birth without other characteristic physical anomalies. Most of the patients develop a severe aplastic anemia and trilineage cytopenia during the first years of life and hematopoietic stem cell transplantation is the only curative treatment. In most of the cases the disease is caused by homozygous or compound heterozygous mutations in the gene MPL encoding the receptor for the hematopoietic growth factor thrombopoietin. The present review summarizes clinical and laboratory data for 96 patients with CAMT, reported since 1990.

Secondary hemophagocytic syndrome in adults: a case series of 18 patients in a single institution and a review of literature

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is rare in adults and is usually fatal without treatment. We present a consecutive series of 18 adults with HLH diagnosed at our institution between 2004 and 2009. All diagnoses were confirmed by pathology. The median age at diagnosis was 56 years (range: 18–73 years), with a male: female ratio of 2:1. Patients uniformly presented with fever. Fifty-five per cent of the patients presented with evidence of hepatomegaly or splenomegaly. All of the patients had at least a bi- or trilineage cytopenia. Elevated liver enzymes, hyperferritinemia, hypertriglyceridemia and hyperfibrinogenemia were seen in 50, 100, 40 and 50% of patients, respectively. The presumed causes were as follows; haematological malignancies (n = 4), post-autologous stem cell transplant (n = 2), infection (n = 2), rheumatologic illness (n = 2), sickle cell disease (n = 1), post-orthotopic liver transplant (n = 1) and idiopathic (n = 3). The median time from suspicion to diagnosis was 5 days (1–27 days). Corticosteroids and/or cyclosporine were the most frequently used treatment regimen. Other agents used were etoposide, IVIG, cyclophosphamide and chemotherapy. The mortality rate was 72%, with multi-system organ failure being the most common cause of death. Median survival time from diagnosis was 35 days. Six patients are alive to date. In a univariate analysis, the presence of fever was the only factor that was statistically significant for predicting a poor prognosis (early mortality) (p = 0.05). In conclusion, a high index of suspicion is the critical factor for early diagnosis. Early treatment with immunosuppressant is warranted, and a thorough diagnostic evaluation to identify the underlying cause should be undertaken. Copyright © 2010 John Wiley & Sons, Ltd.

Classification of Childhood Aplastic Anemia and Myelodysplastic Syndrome

Abstract: Hypoplastic BM disorders in children and adolescents comprise a broad spectrum of disorders. Acquired severe aplastic anemia (SAA), refractory cytopenia of childhood (RCC), a subtype of myelodysplastic syndrome (MDS), and inherited BM failure (IBMF) disorders are the main and most difficult hematological differential diagnoses. Whereas IBMF disorders can often be diagnosed by their clinical features and/or underlying genetic aberrations, the morphological distinction between SAA and hypocellular RCC has been controversial. The histopathological pattern of RCC consists of islands of immature erythroid precursors accompanied by sparsely distributed granulocytic cells. Megakaryocytes are significantly decreased or absent and, rarely, micromegakaryocytes are detected on immunohistochemistry. Because fatty tissue between areas of hematopoiesis can mimic SAA, 2 biopsies are recommended to facilitate the detection of representative BM spaces. Recent data indicate that the response to immunosuppressive therapy is inferior in RCC compared with SAA. Furthermore, approaches to allogeneic hematopoietic transplantation differ. Controlled prospective clinical studies in patients with hypoplastic BM failure disorders will require comprehensive guidelines for diagnosing SAA, RCC, and the different IBMF disorders.

Autoimmune cytopenia in chronic lymphocytic leukaemia: diagnosis and treatment.

Abstract: Autoimmune cytopenia, especially autoimmune haemolytic anaemia (AIHA), appears in 5-10% of patients with chronic lymphocytic leukaemia (CLL). In these patients, the prognosis is not as poor as in those cases in which the cytopenia is due to a massive bone marrow infiltration by the disease, and their treatment requires special considerations. For these reasons, the diagnosis of autoimmune cytopenia should be entertained in any patient with CLL presenting with cytopenia. In patients with autoimmune cytopenia and CLL, treatment is as for idiopathic autoimmune cytopenia, with most patients responding to corticosteroids. For patients not responding to corticosteroids, splenectomy is a reasonable treatment choice. Monoclonal antibodies and thrombopoietin analogues have shown enough activity to support their use, especially within clinical studies, in selected cases not responding to corticosteroids and before splenectomy. In patients with resistant immune cytopenia, the most effective treatment is that of the underlying CLL. Fear of fludarabine-associated AIHA is no longer appropriate in the age of chemo-immunotherapy. Finally, prospective studies are required to better identify the optimal therapy for these patients.

Profile of hemophagocytic lymphohistiocytosis in children in a tertiary care hospital in India

Abstract: To describe the epidemiology, clinical features, laboratory findings, outcome and the difficulties in diagnosis and management of children with Hemophagocytic Lymphohistiocytosis (HLH) in a tertiary children’s hospital in India. Retrospective analysis of case records of all the children with a diagnosis of HLH from December 2006 to December 2008. Tertiary care children’s teaching hospital in Chennai, India. 43 children had a diagnosis of hemophagocytosis, of who only 33 (19 male, mean age 46 months, range 50 days-14 years) met the inclusion criteria based on the HLH-2004 protocol of the Histiocyte Society. The predominant presenting features included prolonged fever and hepatosplenomegaly. CNS symptoms were present in 36%. Anemia (Hb <9gm/dL), and thrombocytopenia (platelets <1,00,000/mm3) were present in 97% and 72%, respectively. Among the biochemical markers, hyperferritinemia was present in 97%, and hypofibrinogenemia and high LDH in 92%. Bone marrow examination showed hemophagocytosis in 84%. Infectious agents were identified in 42% children, with viruses accounting for 2/3 of them (5 Dengue virus, 3 EBV, 1 CMV, 1 TB and 5 bacterial agents). The mean duration between the onset of symptoms and the diagnosis was 16 days. Corticosteroids were the most commonly used immunomodulatory agents (67%), followed by IVIg (64%). Cyclosporine was used in 33% and Etoposide in 15%. Improvement of laboratory parameters was noticed within 5–7 days of starting treatment. Overall survival rate was 76%. HLH should be considered in the differential diagnosis of children with prolonged fever, hepatosplenomegaly and cytopenia. Prompt recognition and appropriate therapy may result in good outcome, particularly in Infection associated HLH.

Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs

Abstract: Background Secondary cytopenias are serious complications following hematopoietic cell transplantation. Etiologies include myelotoxic agents, viral infections, and possibly transplant-related factors such as the intensity of the conditioning regimen and the source of stem cells. Design and Methods We retrospectively analyzed data from 2162 hematopoietic cell transplant recipients to examine the effect of these factors on overall cytopenias occurring after 28 days in hematopoietic cell transplantation. Results Advanced age of the patient, recipient cytomegalovirus seropositivity, unrelated donor status, human leukocyte antigen mismatch and lower doses of transplanted CD34+ cells (≤ 6.4×106/kg) significantly increased the risk of cytopenias after day 28. Non-myeloablative hematopoietic cell transplantation had protective effects on anemia and thrombocytopenia after day 28 (adjusted odds ratio 0.76, probability value of 0.05 and adjusted odds ratio 0.31, probability value of <0.0001, respectively) but not on overall or ganciclovir-related neutropenia. This lack of protection appeared to be due to the use of mycophenolate mofetil in the majority of recipients of non-myeloablative hematopoietic cell transplants. Peripheral blood stem cells did not confer protection from cytopenias when compared to bone marrow. Conclusions Elderly patients appear to be more prone to cumulative toxicities of post-transplant drug regimens, but non-myeloablative conditioning, optimized human leukocyte antigen matching, and higher doses of CD34+ cell infusions may reduce the risk of cytopenia after day 28.

Symptomatic bone marrow involvement in breast cancer--clinical presentation, treatment, and prognosis: a single institution review of 22 cases.

Abstract: Aim: In contrast to marrow micrometastasis, development of symptomatic bone marrow involvement (bone marrow carcinomatosis, BMC) is a rare event in the course of metastatic breast cancer; published evidence on the outcome with systemic treatment is even more scarce. The objective of this study was to provide our institution's experience with the clinical presentation, prognosis, treatment, and associated complications of marrow involvement in breast cancer. Patients and Methods: Twenty- two breast cancer patients with BMC diagnosed between 1995 and 2009 were analyzed. Results: All patients presented with osseous metastases at the time of diagnosis of BMC. Anemia was the most prominent hematologic sign present in 17/22, followed by thrombocytopenia. Cytotoxic treatment was offered to 21/22 of patients. The majority showed an improvement of cytopenia following treatment (10 out of 14 anemic patients, 6 out of 9 thrombocytopenic patients, all 4 leukopenic patients). The complication rate was acceptable, with only 5 grade 3 or 4 events related to cytopenia (febrile neutropenia, bleeding). The estimated median overall survival from the date of BMC diagnosis was 19 months. After 4 years, 4 of the patients were still alive. Interestingly, prognosis from the time of first diagnosis of BMC was independent of the duration of metastatic disease before BMC had been diagnosed. Conclusion: Bone marrow involvement has to be considered in breast cancer patients, in particular in those with bone metastases and otherwise unexplained cytopenia. The peripheral blood smear can serve as a simple diagnostic tool, but the extent of erythroblastosis is not correlated with survival. Even with severe BMC-associated cytopenia, aggressive combination treatment regimens are indicated, since most patients show improved marrow function after chemotherapy and long- lasting survival is possible. Diffuse infiltration of the bone marrow by malignant cells can result in cytopenia and thus poses a difficult problem in the treatment of affected patients. However, despite its clinical relevance, this complication has received little attention. Prostate cancer and gastric adenocarcinoma are the malignancies which are primarily associated with the occurrence of bone marrow carcinomatosis (BMC) (4).

Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation.

Abstract: We describe 70 children with myelodysplastic syndrome (MDS) (refractory cytopenia (n=31) and refractory anemia with excess blasts (n=30) or blasts in transformation (n=9)) who received umbilical cord blood (UCB) transplantation with a single UCB unit and a myeloablative conditioning regimen. Approximately 20% of children had secondary MDS. Median age at transplantation was 7 years and the median follow-up was 3 years. The day-60 probability of neutrophil recovery was 76%; recovery was faster after transplantation of matched or 1-locus mismatched UCB, irradiation-containing conditioning regimen, cell dose >6 × 10(7)/kg and monosomy 7. Risks of treatment failure (recurrent disease or death) were lower in patients with monosomy 7 and transplantations after 2001. The 3-year disease-free survival (DFS) was 50% for transplantations after 2001 compared with 27% for the earlier period (P=0.018). Transplantations after 2001 occurred within 6 months after diagnosis and used UCB units with higher cell dose. DFS was highest in patients with monosomy 7 (61%) compared with other karyotypes (30%), P=0.017. These data suggest that transplantation of mismatched UCB graft is an acceptable alternative for children without a matched sibling or suitably matched unrelated adult donor.

Serum levels of endothelium-derived endocan are increased in patients with untreated acute myeloid leukemia

Abstract: Endocan is a soluble proteoglycan expressed only by vascular endothelium and is also found circulating in the bloodstream. Inflammatory cytokines as well as proangiogenic growth factors increase its expression, and increased serum levels are found in immunocompetent patients with sepsis. We investigated serum endocan levels in patients with untreated acute myeloid leukemia (AML) and AML patients during chemotherapy-induced bone marrow failure. We observed increased levels in 40 AML patients compared with healthy controls, which was also confirmed in a second cohort. The serum levels decreased after intensive chemotherapy and subsequent severe chemotherapy-induced cytopenia, and increased levels were thereafter observed during bone marrow regeneration. However, even for these severely immunocompromized patients, serum endocan levels increased during complicating bacterial infections before a decrease was seen during antibiotic therapy. To conclude, serum endocan is a disease marker in AML, but serum levels are also affected by complicating infections and bone marrow regeneration.

Hematological manifestations of human immunodeficiency virus infection and the effect of highly active anti-retroviral therapy on cytopenia.

Abstract: BACKGROUND The aim of this study is to investigate the hematological manifestations of human immunodeficiency virus (HIV) infection, the risk factors for cytopenia, and the effect of highly active anti-retroviral therapy (HAART) on cytopenia. METHODS Medical records of patients treated for HIV at the Seoul National University Hospital from January 2005 to March 2010 were retrospectively reviewed. To determine the impact of HIV itself, we excluded HIV patients who had other conditions that could have resulted in hematological manifestations. Multiple logistic regression analyses were performed to identify risk factors for cytopenia. RESULTS A total of 621 cases were investigated, and after exclusion, data of 472 patients were analyzed. The frequency of cytopenia was anemia, 3.0% (14/472); neutropenia, 10.0% (47/472); thrombocytopenia, 2.4% (12/472); lymphopenia, 25.7% (121/470); isolated cytopenia, 11.2% (53/472); and bicytopenia, 2.1% (10/472). The leading risk factor for cytopenia identified by multivariate logistic regression methods was AIDS status at initial presentation. After HAART, cytopenia was reversed in the majority of patients (thrombocytopenia, 100%; neutropenia, 91.1%; and anemia, 84.6%). CONCLUSION This study isolated the impact of HIV infection alone on hematologic manifestations and confirmed that these changes were reversible by HAART. Control of the HIV infection will have the main role in the management of hematological manifestations of the virus.

Clinical characteristics of hemophagocytic lymphohistiocytosis related to Kawasaki disease.

Abstract: It is difficult to predict the prognosis or clinical course of secondary hemophagocytic lymphohistiocytosis (HLH) due to the various underlying causes. The authors analyzed the clinical and laboratory findings and outcomes in patients with HLH who had initially been diagnosed with Kawasaki disease (KD), and evaluated the clinical significance of each factor. Among the 21 patients with HLH, 5 had initially been diagnosed with KD and 16 had other etiologies. A comparative analysis was performed for fever duration, presence of cytopenia, serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, fibrinogen, hyponatremia, reactivation, and survival rate in those HLH patients associated with KD (group I) and other causes (group II). In patients in group I, a higher level of reactivation (20%), a lower survival rate (P = .001), higher AST (P = .031) and ferritin (P = .005), and frequent hyponatremia (P = .000) were found compared to patients in group II. Interestingly, patients in group I was older than the average of age of most KD patients. A high index of suspicion on the progression from KD to HLH would be mandatory when the KD patients show elevated AST and ferritin and the presence of hyponatremia, and especially so if the patient is of older age.

Common variable immunodeficiency associated with hepatosplenic T-cell lymphoma mimicking juvenile systemic lupus erythematosus.

Abstract: Common variable immunodeficiency (CVID) is a heterogeneous disorder with susceptibility to infections, autoimmune manifestations, and cancer. To our knowledge, CIVD with T-cell lymphoma mimicking juvenile systemic lupus erythematosus (JSLE) was not described in the literature, and one case was reported herein. An 8-year-old female was admitted in our Pediatric Immunology Unit with a clinical history of hypogammaglobulinemia, recurrent upper respiratory infections, and pneumonias. She had a marked decrease of three serum immunoglobulin isotypes, and the diagnosis of CVID was established. At the age of 17 years, she presented with oral ulceration, nonerosive arthritis, nephritis, serositis, cytopenia, positive antiphospholipid antibodies, and positive antinuclear antibody fulfilling the American College of Rheumatology (ACR) criteria for SLE. She was treated with intravenous methylprednisolone for three consecutive days, and intravenous immunoglobulin, and maintenance therapy of chloroquine, azathioprine and prednisone 40 mg/day. Two months later, she died of septic shock secondary to acute pneumonia. The necropsy showed hepatosplenic T-cell lymphoma with diffuse involvement of bone marrow, spleen, liver, and lungs. The lymphoma cells were positive for CD3 immunostaining and negative for CD20 and lysozyme. In conclusion, the association of CVID and hepatosplenic T-cell lymphoma may simulate JSLE diagnosis.

Haemophagocytic lymphohistiocytosis: a case series from Mumbai.

Abstract: A retrospective review of ten patients (8 girls, 2 boys) admitted over a 9-month period with haemophagocytic lymphohistiocytosis (HLH) is presented. Presenting features included fever and hepatosplenomegaly (10), bleeding manifestations (7), lymphadenopathy (4), skin rash (4), shock (4), jaundice (3), CNS disorder (3), renal failure (2) and arthritis (2). Three infants had familial HLH (FHL) while the other seven patients had acquired (secondary) HLH. Two patients with FHL had very low perforin levels (0 and 0.05%). There was secondary HLH owing to systemic onset juvenile idiopathic arthritis in two patients, and one each had anaplastic large cell lymphoma, measles with pneumonia, disseminated tuberculosis, dengue hemorrhagic fever and lymphoproliferative disorder. Cytopenia affecting two or three lineages in peripheral blood was present in all while haemophagocytosis in bone marrow was documented in nine patients .Other important laboratory parameters were raised ferritin (9), raised LDH (9), hypertriglyceridaemia (7) and hypofibrinogenaemia (5). The patients were treated according to the HLH2004 protocol. Diagnosis of HLH should be considered early in patients presenting with unremitting fever, hepatosplenomegaly and cytopenias as without appropriate treatment HLH is usually fatal.

Acquired hemophagocytic lymphohistiocytosis associated with multiple myeloma.

Abstract: Acquired or secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening hyperinflammation syndrome caused mostly by various infectious agents, autoimmune disorders or malignancy. So far, only anecdotal cases of sHLH associated with multiple myeloma have been published. We provide a review of all these reports and include a previously not published case of myeloma-associated sHLH in a 59-year-old male with complex partial epilepsy. Due to aggressive course of sHLH, increased awareness is indicated in all patients with malignancies which develop unremitting fever, cytopenia and splenomegaly. Early diagnosis and immediate introduction of adequate therapy is crucial for the outcome of HLH.

Idiopathic bone marrow dysplasia of unknown significance (IDUS): definition, pathogenesis, follow up, and prognosis.

Abstract: Minimal diagnostic criteria for myelodysplastic syndromes (MDS) include constant cytopenia recorded for at least 6 months, dysplasia, and exclusion of other causes of cytopenia and dysplasia. However, there are patients with dysplastic bone marrow features with or without a karyotype, who have only mild if any cytopenia. This condition has been termed idiopathic dysplasia of unknown significance (IDUS). Out of a series of 1,363 patients with suspected MDS or mild cytopenia seen between 1997 and 2010, we have identified 10 patients with IDUS, and analyzed their clinical course and outcome as well as features potentially involved in disease-evolution. Follow-up ranged between 2 and 13 years. Progression to an overt myeloid neoplasm was observed in 4 patients: two progressed to frank MDS, one to chronic myelomonocytic leukemia, and one to a myelodysplastic/myeloproliferative neoplasm exhibiting 5q-and JAK2 V617F. Consecutive studies revealed that most IDUS patients have an adequate production of erythropoietin (EPO) and sufficient numbers of EPO-responsive erythroid progenitors, features rarely seen in MDS. The erythropoiesis-promoting JAK2 mutation V617F was only detectable in one case. We hypothesize that the dysplastic clone in IDUS cannot manifest as frank MDS because i) the clone retains responsiveness against EPO, and ii) an adequate EPO-production counteracts anemia. Evolution of IDUS to low risk MDS may thus depend on the biological properties of the clone as well as patient-related factors such as EPO production. The latter often decreases with age and may thus explain why MDS often manifests in the elderly.

A matter of debate in chronic lymphocytic leukemia: is the occurrence of autoimmune disorders an indicator of chronic lymphocytic leukemia therapy?

Abstract: Purpose of reviewAutoimmune cytopenia is a noninfrequent complication of chronic lymphocytic leukemia (CLL) classified into simple and complex autoimmunity, on the basis of the absence or the concomitance of disease progression. Simple-refractory and complex autoimmunity indicate the need of treatme

A prospective observational study of the effect of platelet transfusions on levels of platelet-derived cytokines, chemokines and interleukins in acute leukaemia patients with severe chemotherapy-induced cytopenia

Abstract: Platelet concentrates contain soluble mediators derived from both platelets and contaminating leukocytes. During platelet transfusion these mediators are transferred, and transfusion-induced modulation of the cytokine network may then occur, possibly contributing to transfusion reactions, immunomodulation, or affecting residual leukemic cells. In this prospective observational study, we investigate the effect of platelet transfusion on the systemic levels of platelet-derived cytokines, chemokines and interleukins in an unselected group of acute leukaemia patients with severe chemotherapy-induced cytopenia. We investigated 31 platelet transfusions involving pre-storage, white blood cell-reduced, gamma-irradiated or pathogen-inactivated, photochemically-treated platelet concentrates received by 10 unselected patients. Peripheral blood plasma samples were collected before, immediately after, one hour, and 24 hours after the transfusions. Sampling from platelet concentrates was performed immediately before transfusion. A total of 31 soluble mediators were examined. Ten healthy controls matched for age and gender were included. Despite heterogeneity in patients and platelet concentrates, significantly increased plasma concentrations were detected for the platelet-derived mediators, platelet-derived growth factor, β-thromboglobulin, transforming growth factor-β (TGF-β), CCL5, and CXCL4, 1 hour and/or immediately after platelet transfusions. The plasma levels of vascular endothelial growth factor and soluble CD40 ligand were not altered by platelet transfusion. Certain interleukins (IL-1β, IL-2, IL-4, IL-6, IL-9, and IL-12), as well as interferon-γ showed a minor, transient decrease in systemic plasma levels during the first hour following transfusion. Platelet transfusions modulate the systemic cytokine network in acute leukaemia patients with severe, chemotherapy-induced cytopenia.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

Abstract: Since the 20th century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. From 1989–2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with 60Co gamma rays or 5–15MV photons. The fraction size ranged from 10–200 cGy and the total dose per treatment course from 30–1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

Successful use of tocilizumab in a patient with rheumatoid arthritis following severe pancytopenia during etanercept therapy.

Abstract: Severe cytopenia, including neutropenia and anemia, may occasionally occur during anti-tumor necrosis factor α (TNF-α) therapy. However, its mechanism is poorly understood, and little is known concerning the rationale of the choice of biologic therapy after a severe episode of cytopenia. The authors present the case of a 68-year-old rheumatoid arthritis patient in whom severe pancytopenia developed soon after the initiation of etanercept therapy. After resolution, the interleukin 6 receptor-blocking agent tocilizumab was introduced, which resulted in long-lasting complete remission of the rheumatoid arthritis without any adverse effects. The apoptosis-inducing effects of 3 TNF-α blockers and tocilizumab on peripheral blood mononuclear cells of the patient were compared by means of annexin V and propidium iodide labeling and flow cytometry. In concert with the clinical events, the anti-TNF-α agents demonstrated significantly higher apoptotic activities than that of tocilizumab. Tocilizumab appeared safe after anti-TNF-α-induced cytopenia possibly caused by apoptosis induction.

Myelodysplastic Syndromes/Neoplasms: Morphological and Immunohistochemical Features and Standard Evaluation

Abstract: Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic stem cell disorders characterised by dysplasia in at least one major myeloid cell line and signs of bone marrow insufficiency with subsequent cytopenia. The updated WHO classification of MDS defines several subtypes including refractory cytopenia (anemia, neutropenia and/or thrombocytopenia), refractory anemia (RA) with ring sideroblasts (RARS), refractory cytopenia with multilineage dysplasia and RA with excess of blast cells (RAEB). While isolated recfractory neutropenia and thrombocytopenia are very rare disease categories, refractory cytopenia with multilineages dysplasia, RARS and refractory anemia with excess of blasts are much more frequently observed. One peculiar subtype of MDS is defined by the presence of an isolated cytogenetic abnormality, in particular del(5q). The diagnostic approach to MDS should include not only cytomorphological evaluation of blood and bone marrow smears but also histological analysis of a bone marrow trephine biopsy specimen and molecular/cytogenetic findings. Some rare subvariants of MDS are not included in the WHO classification system but represent special disorders which can only be recognised by histological investigation: (1) hypocellular MDS, (2) MDS with fibrosis, and (3) MDS associated with systemic mastocytosis (SM) in the setting of a so-called SM-AHNMD (“associated clonal hematologic non-mast cell disorder”). While cytological atypia of blood cells is easilyrecognisable in smear preparations only histologic investigation of the bone marrow enables detection of reticulin fibrosis, small blast cell infiltrates and clustering of megakaryocytes. Therefore, immunohistochemical analysis with antibodies against the stem cell-associated antigen CD34, at least one platelet-related antibody (CD42, CD61), and an antibody against mast cell tryptase is recommended in all cases of suspected MDS. Differential diagnostic aspects include a broad variety of non-neoplastic and neoplastic disorders, especially overt acute myeloid leukemia (AML) but also systemic mastocytosis considering that more than one neoplasm may develop and co-exist in the same patient.

Etanercept-induced lupus accompanied by hemophagocytic syndrome.

Abstract: Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder characterized by an excessive activation of macrophages, such as may occur in the setting of lupus. A 62-year-old Japanese woman treated with etanercept for rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and hyperferritinemia. Simultaneously, lupus-like features including pleuritis, hypocomplementemia, and positive autoantibodies were observed. She was diagnosed with HPS related to etanercept-induced lupus, and underwent immunosuppressive therapy with successful recovery. To our knowledge, this is the first case of etanercept-induced lupus accompanied by HPS. This case suggests that HPS should be considered as a complication during TNF-α inhibitor therapy.

Parvovirus B19-associated hemophagocytic lymphohistiocytosis in a child with precursor B-cell acute lymphoblastic leukemia under maintenance chemotherapy

Abstract: Development of hemophagocytic lymphohistiocytosis (HLH) is quite rare among acute lymphoblastic leukemia (ALL) patients. We present a 3-year-old boy with precursor B-cell ALL, who was complicated by HLH because of parvovirus B19 infection during maintenance chemotherapy. Remarkable erythroid hypoplasia, giant normoblasts, and hemophagocytosed macrophages in bone marrow were important clues for the diagnosis. The patient was successfully treated with high-dose steroids and intravenous immunoglobulins. To our knowledge, this is the first report describing parvovirus B19-associated HLH in ALL. Our case highlights that parvovirus B19 can cause HLH, a potentially fatal disorder, and prolonged unexpected cytopenia in childhood ALL.

Lymphoma-associated hemophagocytic syndrome (LAHS) in advanced-stage mycosis fungoides/Sézary syndrome cutaneous T-cell lymphoma.

Abstract: Background Lymphoma-associated hemophagocytic syndrome (LAHS) is a rare clinicopathological entity. It has been described with primary cutaneous lymphomas, mostly of the subcutaneous panniculitis-like T-cell type, and only once with cutaneous T-cell lymphoma (CTCL). Methods We report the cases of 5 patients with epidermotropic CTCL who developed LAHS and died shortly thereafter. Unlike LAHS associated with systemic lymphomas, these CTCL-associated LAHS were late events, occurring several years after the initial lymphoma diagnosis. Limitations The small number of patients reported renders definite conclusions difficult. Further reports would be needed to confirm our statements. Conclusion LAHS is probably underdiagnosed in CTCL patients with acute inflammatory symptoms suggestive of infections but should be considered, especially when cytopenia and elevated triglyceride and ferritin levels are present.