Abstract in English:BACKGROUND: In 2006 the Hematology Service of Hospital Maciel published its experience with peripheral blood progenitor cell harvesting for autologous stem cell transplantation using Filgen JP (Clausen Filgrastim). After mobilization with a mean filgrastim dose of 78 mcg/Kg, 4.7 x 10(6) CD34+ cells/Kg were obtained by apheresis. Age above 50, multiple myeloma as underlying disease and a malignancy that was not in remission were identified as frequent characteristics among patients showing complex mobilization. OBJECTIVE: The aim of this study was to compare stem cell mobilization using different brands of filgrastim. METHODS: One hundred and fifty-seven mobilizations performed between 1997 and 2006 were analyzed. This retrospective analysis comparative two groups of patients: those mobilized with different brands of filgrastim (Group A) and those who received Filgen JP (Clausen Filgrastim) as mobilizing agent (Group B). A cluster analysis technique was used to identify four clusters of individuals with different behaviors differentiated by age, total dose of filgrastim required, number of apheresis and harvested CD34+ cells. RESULTS: The mean total dose of filgrastim administered was 105 mcg/Kg, the median number of apheresis was 2 procedures and the mean number of harvested stem cells was 4.98 x 10(6) CD34+ cells/Kg. No significant differences were observed between Groups A and B regarding the number of apheresis, harvested CD34+ cells and number of mobilization failures, however the total dose of filgrastim was significantly lower in Group B. CONCLUSIONS: Among other factors, the origin of the cytokine used as mobilizing agent is an element to be considered when evaluating CD34+ cell mobilization results.
Abstract in English:BACKGROUND: The detection of molecular and cytogenetic alterations is important for the diagnosis, prognosis and classification of myeloproliferative neoplasms. OBJECTIVE: The aim of this study was to detect the following mutations: JAK2 V617F, JAK2 exon 12 and MPL W515K/L, besides chromosomal abnormalities. Furthermore, molecular and cytogenetic alterations were correlated with the leukocyte and platelet counts, hemoglobin levels and age in all patients and with the degree of fibrosis in primary myelofibrosis cases. METHODS: Twenty cases of polycythemia vera, 17 of essential thrombocythemia and 21 of primary myelofibrosis were selected in the Hematology Department of the Universidade Federal de São Paulo (UNIFESP) between February 2008 and December 2009. The JAK2 V617F, JAK2 exon 12 mutations, MPL W515K and MPL W515L mutations were investigated by real-time PCR and direct sequencing. G-band karyotyping and fluorescence in situ hybridization were used to detect chromosomal abnormalities. RESULTS: Chromosomal abnormalities were observed only in polycythemia vera (11.8%) and primary myelofibrosis cases (17.6%), without correlation to clinical data. Chromosomal abnormalities were not detected by fluorescence in situ hybridization. The JAK2 V617F mutation was observed in polycythemia vera (90%), primary myelofibrosis (42.8%) and essential thrombocythemia (47%). Patients with JAK2 V617F-negative polycythemia vera had lower platelet and leukocyte counts compared to V617F-positive polycythemia vera (p-value = 0.0001 and p-value = 0.023, respectively). JAK2 V617F-positive and MPL W515L-positive primary myelofibrosis cases had a higher degree of fibrosis than V617F-negative cases (p-value = 0.022). JAK2 exon 12 mutations were not detected in polycythemia vera patients. The MPL W515L mutation was observed in one case of primary myelofibrosis and in one of essential thrombocythemia. The MPL W515K mutation was not found in patients with essential thrombocythemia or primary myelofibrosis. The MPL W515L-positive patient with primary myelofibrosis had more severe anemia than other patients with primary myelofibrosis. CONCLUSIONS: This study demonstrates that karyotyping for JAK2 and MPL mutations is useful in the diagnosis of myeloproliferative neoplasms. The precise pathogenetic contribution of these alterations is still unclear. However, this study adds more information about the pathophysiology of polycythemia vera, essential thrombocythemia and primary myelofibrosis.
Abstract in English:BACKGROUND: Secondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16). OBJECTIVE: To study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia. METHODS: The clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7. RESULTS: The cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012). CONCLUSION: This study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms.
Abstract in English:OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m²) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m²) and methotrexate (8 g/m² only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.
Abstract in English:BACKGROUND: Iron deficiency is the most common disorder in the world, affecting approximately 25% of the world`s population and the most common cause of anemia. OBJECTIVE: To evaluate the efficacy and safety of intravenous iron sucrose (IS) in the treatment of adults with iron deficiency anemia METHODS: Eighty-six adult patients with iron deficiency anemia, who had intolerance or showed no effect with oral iron therapy, received a weekly dose of 200 mg of intravenous iron sucrose until the hemoglobin level was corrected or until receiving the total dose of intravenous iron calculated for each patient RESULTS: The mean hemoglobin and serum ferritin levels were 8.54 g/dL and 7.63 ng/mL (pre-treatment) and 12.1 g/dL and 99.0 ng/mL (post-treatment) (p-value < 0.0001), respectively. The average increases in hemoglobin levels were 3.29 g/dL for women and 4.58 g/dL for men; 94% of male and 84% of female patients responded (hemoglobin increased by at least 2 g/dL) to intravenous iron therapy. Correction of anemia was obtained in 47 of 69 (68.1%) female patients and in 12 of 17 male (70.6%) patients. A total of 515 intravenous infusions of iron sucrose were administered and iron sucrose was generally well tolerated with no moderate or serious adverse drug reactions recorded by the investigators. CONCLUSIONS: Our data confirm that the use of intravenous iron sucrose is a safe and effective option in the treatment of adult patients with iron deficiency anemia who lack satisfactory response to oral iron therapy. Intravenous iron sucrose is well tolerated and with a clinically manageable safety profile when using appropriate dosing and monitoring. The availability of intravenous iron sucrose would potentially improve compliance and thereby reduce morbidities from iron deficiency.
Abstract in English:OBJECTIVE: The aim of this study was to verify if ABO phenotypes are associated with allergic rhinitis. METHODS: 168 patients with allergic rhinitis and 168 control individuals from the same geographical region and paired by gender and age were enrolled in the study. ABO phenotypes were identified in red blood cells using the hemagglutination technique. The Fisher exact and chi-squared tests were employed to compare proportions. Statistical significance was set for an alpha error of 5% (p-value < 0.05). RESULTS: The overall differences in the frequencies of the ABO phenotypes of patients and controls were marginal (χ2: 7.569; degrees of freedom (DF): 3; p-value = 0.055) however the O blood group was associated with allergic rhinitis (χ2: 5.764; DF: 1; p-value = 0.016; OR: 1.735; CI 95%: 1.127-2.673). The differences in the frequencies of the O phenotype in patients and controls were statistically different for men (χ2: 8.520; DF: 1; p-value = 0.003) but not for women (χ2: 0.6375; DF: 1; p-value = 0.4246). The A phenotype was associated with protection (OR: 0.4385; CI 95%: 0.2043-0.9415; p-value = 0.049) and the O phenotype was associated with susceptibility (OR = 2.789; CI 95%: 1.385-5.616; p-value = 0.005) to allergic rhinitis only for men. CONCLUSION: The O blood group phenotype is associated with allergic rhinitis in male but not in female patients.
Abstract in English:Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging.
Abstract in English:Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia (IDA) because of its effectiveness and low cost. But unfortunately in many iron deficient conditions, oral iron is a less than the ideal treatment mainly because of adverse events related to the gastrointestinal tract as well as the long course required to treat anemia and replenish body iron stores. The first iron product for intravenous use was high-molecular-weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to prescribe intravenous iron in the treatment of iron deficiency anemia for many years. In 1999 and 2001, two new intravenous iron preparations (ferric gluconate and iron sucrose) were introduced into the market as safer alternatives to iron dextran. Over the last five years, three new intravenous iron dextran-free preparations have been developed and have better safety profiles than the more traditional intravenous compounds, as none require test doses and all these products are promising in respect to a more rapid replacement of body iron stores (15-60 minutes/infusion) as they can be given at higher doses (from 500 mg to more than 1000 mg/infusion). The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, safety profile and toxicity of intravenous iron for the treatment of iron deficiency anemia.
Abstract in English:The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.
Abstract in English:Aplastic anemia is an uncommon complication of thymoma and is extremely infrequent after the surgical removal of a thymic tumor. Aplastic anemia is a result of marrow failure and is characterized by peripheral pancytopenia and severely depressed marrow cellularity; it may be an autoimmune manifestation of thymoma. As thymoma-associated hematological dyscrasias, which include pure red cell aplasia, aplastic anemia and myasthenia gravis, are supposed to be of immunologic origin, two cases of very severe aplastic anemia following the resection of lymphocytic thymomas treated with immunosuppression are herein presented.
Abstract in English:Acute promyelocytic leukemia is potentially a highly curable type of leukemia that usually presents with pancytopenia, coagulopathies and bleeding. We describe a case of an unusual presentation of acute promyelocytic leukemia. A 53 year-old male was admitted complaining of pain and weakness in his legs. He presented at examination a spastic paraparesis with a sensitive level at the eighth thoracic medullar (T8) segment. Magnetic resonance imaging showed a posterolateral extradural mass from T6 through T8 segments with medullar compression. A complete blood count showed anemia, thrombocytopenia and the presence of promyelocytes and blasts. Marrow examination was compatible with the diagnosis of acute promyelocytic leukemia by cytogenetics and polymerase chain reaction for the PML-RARα gene. He was treated with all-trans-retinoic acid therapy plus daunorubicin and presented an all-trans-retinoic acid syndrome. Despite hematological remission, the patient presented neurologic deterioration and had to be treated with radiotherapy (total dose 3000 cGy) of the extradural lesion. The patient evolved with severe sepsis and died without any recovery from his neurologic deficit. Extramedullary infiltration is a very rare complication in acute promyelocytic leukemia. Most cases are related to relapse after initial treatment with all-trans-retinoic acid. The skin and the central nervous system are the most frequently involved sites. This is possibly the first case reported of this condition in which the patient had a symptomatic extradural mass.
Abstract in English:Visceral leishmaniasis (VL) is a severe systemic infectious disease.(1) It has been recognized as an opportunistic disease in patients infected with human immunodeficiency virus (HIV).(2,3) The analysis of the bone marrow of patients co-infected with VL and HIV showed dysplasia of erythroid, granulocytic and megakaryocytic lineages (Figure 1), besides the presence of plasmacytosis, cytoplasmic bodies, hemophagocytosis, granuloma and intracellular and extracellular leishmania amastigotes (Figure 2). These findings are found in the analysis of bone marrow of patients co-infected with HIV and VL; knowledge of these findings may be useful for the diagnosis and prognosis of patients.