Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy, characterized by thrombocytopenia and an increased risk for thrombotic complications secondary to the formation of IgG antibodies (Ab), recognizing a complex of heparin (H) and PF4. Using the 4T clinical score for HIT and the presence of heparin-associated Ab assayed by enzyme-linked immunosorbent assay and heparin-induced platelet aggregation, we define the phenotype of three groups of patients: 51 H/PF4/Ab patients with antibodies and without thrombocytopenia; 50 patients with thrombocytopenia (HIT) and 53 patients with thrombosis (HITT). In these patients we studied four polymorphisms: Fc gamma RIIA-H131R, GpIIb/IIIa-HP-1, PECAM1-L125V (in linkage-disequilibrium with S563N and R670G), and Fc gamma RIIIA-F158V, to understand if these variations may influence the different phenotypes of the patients. There were no difference in genotype or allele frequencies between controls and the three groups of patients. Afterward, we created a genotype score for multiple risk alleles for thrombosis considering as risk genotype Fc gamma RIIA R/R131, HPA-1a/b, and PECAM1-V/V125. These polymorphisms were overrepresented in HITT patients, ascertained by a permutation test (10 000 replicates) p = 0.0198 for the two-single-nucleotide polymorphism (SNP) model and p = 0.0119 for the three-SNP model. The calculated odds ratio for thrombosis was 4.01[CI: 2.30-6.96] in the case of the presence of two at risk genotypes and 8.002 [CI: 4.59-13.93] if all the three at risk genotypes were present. In conclusion these polymorphisms could contribute to the risk of thrombotic complications in HIT.
Although essential in the management of AML, there is little information quantitating transfusion requirements for these patients. We evaluated 111 consecutive adults treated for AML, showing that approximately 150 blood donors are required to adequately cater for a single patient's complete therapy with little variation for age, prognostic group or intensity of treatment.
Venous thromboembolism is a common problem in cancer patients. It complicates both the surgical management of those with cancer and has been associated with varying risk for the development of clinical thromboembolism in patients receiving chemotherapy. Unfractionated and low-molecular-weight heparin have been validated both in terms of their efficacy and safety, in the prevention of venous thromboembolic disease in cancer patients undergoing surgical intervention and for the primary treatment and secondary prevention of recurrent venous thromboembolism. Beyond their uses in the prevention and treatment of thrombosis, low-molecular-weight heparins have recently been shown to prolong survival in patients with solid tumour malignancy.
We describe a 28-year-old man treated with hydroxyurea for sickle cell anemia, who was admitted to the University Hospital with an acute myocardial infarction. The patient had evolved high hematocrit values during his long-term hydroxyurea treatment, suggesting a correlation between a possible increment in blood viscosity and the coronary occlusion without previous lesions. Indeed, several studies associate vasocclusive episodes and severe clinical course with high viscosity. Although hydroxyurea is considered an effective therapeutic option for these patients care should be taken to monitor hematocrit levels and possible complications. Hematocrit and hemoglobin values of above 30% and 10.5 g/dl in SS patients on hydroxyurea therapy should be avoided or closely monitored.
Introduction: The question as to whether the incidence of leukemias and malignant lymphomas among the clean-up workers increased in 18 years after the catastrophe is still a point of much controversy. Precise diagnosis of the main forms of hematopoietic malignancies and comparison of these data with those in the general population will be helpful in estimating the relative contribution of the radiation factor to the overall incidence of such pathologies.Materials and methods: In all, 187 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers were analyzed in Ukrainian Reference Laboratory in 1996-2003. A total of 1942 consecutive patients of general population, mainly the residents of Kyiv city and district, diagnosed in Reference Laboratory at the same period comprised the group of comparison. The morphology and cytochemistry of bone marrow and peripheral blood cells were studied. Immunocytochemical techniques (PAP, APAAP, ABC) and the panel of monoclonal antibodies to differentiation antigens of leukocytes were employed for immunophenotyping leukemic cells.Results: Various types of malignant diseases of hematopoietic and lymphoid tissues were registered in Chernobyl clean-up workers under study including myelodysplastic syndromes (nine patients), acute lymphoblastic leukemia (eight) and acute myeloblastic leukemia (31), chronic myeloid leukemia (17), multiple myeloma (17) and other forms of chronic myeloproliferative and lymphoproliferative diseases including B-cell chronic lymphocytic leukemia (49 patients).Conclusion: The verified diagnosis of tumors of hematopoietic malignancies according to modern classification (EGIL, WHO) could be the prerequisite for further analytical epidemiology study of leukemias that may be related to the Chernobyl accident.
We aimed to study the effect of iron deficiency anemia (IDA) on immunity. In 32 children with IDA and 29 normal children, the percentage of T-lymphocyte subgroups, the level of serum interleukin-6 (IL-6); and the phagocytic activity, the oxidative burst activity of neutrophils and monocytes and the levels of immunoglobulins were compared. There was no difference in the distribution of T-lymphocyte subgroups. The mean IL-6 levels was 5.6 +/- 3.9 pg/ml in children with IDA and 10.3 +/- 5.3 pg/ml in the control group (P < 0.00 1). The percentage of neutrophils with oxidative burst activity when stimulated with pma was 53.4 +/- 32.7% in children with IDA and 81.7 +/- 14.3% in the control group (P = 0.005). The percentage of monocytes with oxidative burst activity was 13.8 +/- 11.7% in children with IDA and 35 +/- 20.0% in the control group (P < 0.001) when stimulated with pma. and 4.3+/-3.1 versus 9.7+/-6.0% (P = 0.008) when stimulated with fMLP. The ratio of neutrophils with phagocytic activity was 58.6+/-23.3% in the anemic group; and 74.2 +/- 17.7% in the control group (P = 0.057). The ratio of monocytes with phagocytic activity was 24.3+/-12.0% in the anemic group; and 42.9+/-13.4% in the control group (P = 0.001). IgG4 level was 16.7+/-16.6mg/dl in children with IDA and 51.8+/-40.7mg/dl in healthy children (P < 0.05). These results suggest that humoral, cell-mediated and nonspecific immunity and the activity of cytokines which have an important role in various steps of immunogenic mechanisms are influenced by iron deficiency anemia.
Systemic multiagent hemotherapy has been used to treat aggressive forms of primary cutaneous T-cell lymphomas (CTCL) with controversial results. Our objective was to retrospectively assess efficacy and toxicity of ESHAP (etoposide, cisplatin, high-dose aracytine, methylprednisolone) in patients with advanced CTCL. A total of 11 patients with aggressive primary CTCL, treated with the ESHAP protocol between 1995 and 2002, were studied. Two patients achieved complete remissions lasting 30+ and 6+ months, seven had partial remissions of short duration, one had stable disease and one experienced disease progression. ESHAP was poorly tolerated because of prolonged myelosuppression (91%) and infectious complications (82%). Our results suggest that ESHAP has a poor risk/benefit ratio in advanced CTCL because of the low number of complete remissions, the short duration of partial remissions and its high-grade toxicity.
Introduction: The clinical efficacy of doxorubicin is severely limited by its cardiotoxicity. The currently noninvasive techniques used to detect this complication lack sensitivity to identify its early stages. Nitric oxide (NO) is a free radical that has been implicated in the etiology of doxorubicin-induced cardiotoxicity. In the present study, we investigated whether plasmatic NO levels can be used as a noninvasive and reliable biomarker of doxorubicin-induced cardiotoxicity.Materials and methods: Two groups of six spontaneously hypertensive rats (SHR) were used for the experiment. Group 1 received 1.5 mg/kg intraperitoneal (IP) doxorubicin weekly for up to 9 weeks. Group 2 (Control) received nine weekly IP injection of 0.5 cm(3) saline. Plasmatic NO levels and cardiac ejection fraction (EF%) were determined. Ventricular biopsies were analyzed by light microscopy according with the Billinghan score.Results: Doxorubicin treatment significantly increased plasmatic NO concentration (35.30+/-5.63 muM versus 14.72+/-2.66 muM in control animals, n = 6, P < 0.05). In addition, doxorubicin decreased EF by 23% approximately (from 77.00+/-3.89 in controls, to 59.00+/-5.61 in doxorubicin-treated animals, n = 6, P < 0.05). The mean score of histological cardiac damage was 2.33+/-0.33 for doxorubicin-treated versus 0.08+/-0.08 for controls, n = 6, P < 0.001.Discussion: Our results revealed a correlation between plasmatic NO levels, systolic function and histopathological myocardial damage. Therefore, it is plausible to postulate that plasmatic NO levels could be used as a biomarker for myocardial damage in doxorubicin-treated SHR, and may be a potential tool for noninvasive evaluation of doxorubicin-induced toxicity in humans.
Secondary iron overload is associated with significant mortality and morbidity. Although new, less invasive techniques are becoming available, the most acceptable and readily accessible way to assess iron overload is to measure hepatic iron by liver biopsy. In this study, we report on serial liver biopsies (at least 2) in a cohort of transfusion-dependent patients (49) on long-term desferrioxamine treatment. There was no significant change in liver iron concentrations (LIC) even in the medication-compliant patients, although there was an upward trend (not statistically significant) in the poorly compliant patients. Fibrosis was present in both HCV RNA-positive and -negative patients, but was more common in positive patients and there was also a significant relationship between fibrosis and hepatic iron concentration. Liver iron levels appear to be maintained in patients who are compliant to desferrioxamine treatment, but overall there is little evidence of significant improvement in liver iron in these patients and in the group as a whole.
In a retrospective study we have sought to determine whether the administration of angiotensin-I-converting enzyme inhibitors (ACEI) influences the outcome of patients with multiple myeloma (MM). Patients with MM who underwent autologous peripheral blood stem cell transplantation (PBSCT) (n = 168) were studied. Patients taking ACEI alone or in combination with other antihypertensive agents during the hospital admission for PBSCT were allocated to the ACEI group (n = 25; 15%). Patients from the non-ACEI group (n = 143; 85%) were taking other or no antihypertensive medication. Patients taking ACEI had worse overall survival (OS) compared to patients not taking ACEI (38.7 versus 73.3 months after diagnosis; P = 0.025). Among patients with hypertension, both OS and progression-free survival were significantly shorter in patients taking ACEL There were no significant differences between the studied groups in standard prognostic parameters for MM (age, albumin, beta 2-microglobulin, IPI and Durie-Salmon stage, LDH, CRP, performance status) or in engraftment. The mortality in our study has been mostly myeloma related. In conclusion, according to our findings, ACEI administered during PBSCT have adverse effect on survival of patients with MM.
This presentation begins to discuss the findings of an ongoing doctoral study that arose as the result of clinical experience, previous studies and ongoing reflection. Building on the work of Frankl [1] this study explores the search for meaning in the context of living with cancer. In this study people with cancer share their experience of trying to make sense of their disease and the treatments they underwent. Some of the findings that have begun to emerge include: the search for meaning is ongoing, multifaceted and may be lived out in a variety of ways, living with cancer and the treatment it demands brings many changes some of which lead to a sense of loss of control, there are a multitude of relationships involved which may help or cause distress to the person dealing with cancer, the health care team while often supportive sometimes failed to see the needs of those they cared for, while people with cancer value the expertise and knowledge of the health care team they also want the team to demonstrate compassion and sensitivity while delivering care and information, while a few people had found particular meaning to aspects of their experience all recognized that the ongoing process of searching to find meaning continues after treatment finishes. It is hoped that by listening to the experiences of these individual people living with cancer the insights gained will support the health care team in their efforts to help those undergoing treatment for cancer.
Allogeneic stem cell transplantation with reduced-intensity conditioning (RIC) can be offered to patients who are ineligible for high-dose conditioning because of their age or comorbidities. Malignant haematological diseases have so far been the most common indication of this new treatment modality; it has been less often used for nonmalignant diseases, and there are only a few reports of RIC and allotransplantation to treat acquired severe aplastic anaemia (SAA). We report two elderly patients (62 and 65 years of age) with SAA who underwent RIC (fludarabine + cyclophosphamide + ATG) and HLA-identical sibling allogeneic blood stem cell transplantation. Two important findings emerged. First, both of our patients who had failed standard immunological treatments and had a heavy transfusion history experienced successful engraftment after RIC and blood allografting, and one of them continues in full haematological remission 20+ months post-transplant. Secondly, the other patient died of Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (PTLD) soon after engraftment, which implies that even if PTLD has been described in only few single cases after RIC, it may also complicate RIC allotransplants.
Antiapoptotic proteins like the inhibitor of apoptosis proteins (IAPs) are molecular markers potentially useful for the characterization of acute myeloid leukemia (AML). We screened 92 adults with de novo AML for the protein expression of various IAPs, Bcl-2 family members and the proform of Caspase-3 using quantitative immunoblot and flow cytometry. XIAP expression correlated with myelomonocytic French-American-British (FAB) subtypes M4/M5 (P<0.05) and expression of monocytic markers (CD 14, CD 36; P <0.05; CD 4, HLA-DR; P <0.01) in AML blasts. In addition, XIAP was overexpressed in normal monocytes but undetectable in granulocytes. In ANIL, XIAP expression was significantly lower in patients with favorable than intermediate or poor cytogenetics (n = 74; P < 0.05). In total, 62 of the examined patients were treated according to the German ANIL Cooperative Group (AMLCG) 92 protocol. These patients were analyzed for prognostic significance of apoptosis-related proteins. Patients expressing low levels of XIAP enjoyed better overall survival than patients expressing high amounts of XIAP (mean, 9 (n=41) versus 19 months (n=21); P <0.05). Other IAPs, most importantly Survivin, were of no prognostic value. We conclude that XIAP but not other IAP family members is associated with monocytic differentiation in normal and malignant myelopoiesis, and may be of prognostic significance for overall survival in adult de novo AML.
INTRODUCTION:Surgical biopsy examination is the gold standard for lymphoma diagnostics. However, fine-needle aspiration cytology (FNAC) offers several advantages in that it is quick, inexpensive, and the aspiration procedure has very few complications. This prospective study compares the diagnostic outcome between FNAC and surgical biopsy.MATERIALS AND METHODS:A total of 103 patients (>15 years) with lymphadenopathy and accessible lymph nodes underwent both diagnostic procedures. Immunophenotyping was performed on both FNAC and histopathological specimens. The updated KIEL classification was used for primary diagnosis and the WHO classification for reclassification.RESULTS:FNAC- and histopathology-based diagnoses were concordant in 76 patients. In 10 patients, there was a major diagnostic discordance: four differed with regard to degree of malignancy (low- versus high-grade NHL), three lymphoma versus reactive changes, and three regarding Hodgkin's lymphoma versus anaplastic large cell lymphoma. In 10 patients there was some (minor) discordance regarding subclassification: in eight patients the results of immunophenotyping differed, in two cases there were discrepancies in the cell type classification. In the remaining seven cases, there were diagnostic difficulties due to an insufficient sample. two serious adverse events occurred following surgical biopsy.CONCLUSIONS:FNAC is an accurate method in the diagnosis of lymphomas when the cytologic diagnosis is corroborated by immunophenotyping. However, an increasing use of FNAC for primary diagnosis and classification of lymphomas may result in a loss of archival tissue for complementary analyses, reclassification, and research purposes. In addition, some of the lymphoma entities are impossible to diagnose with use of the FNAC technique.
A synergistic effect of fludarabine (FLU) and cyclophosphamide (CY) has been extensively demonstrated in the treatment of chronic lymphoproliferative disorders (CLD), although a high incidence of severe neutropenia and infectious complications, particularly in elderly patients, have been reported. Based on a previous clinical experience in elderly CLD patients treated with a combination of low-dose intravenous (i.v.) FLU and CY in whom we obtained good response rates and negligible toxicity, we tested efficacy and safety of the new oral formulation of FLU combined with CY at low doses. A total of 28 elderly patients with relapsed/refractory or untreated CLD were treated with oral FLU and CY (25 and 150 mg/m2 respectively, both for 4 days every 4 weeks). The treatment design consisted in four consecutive courses and the median value of courses per patient was 3. Overall, 25 out of 28 evaluable patients were responsive to the treatment (six CR and 19 PR; ORR 89%), while the remaining three patients did not show any appreciable response (two progressive and one stable disease). Hematological toxicity was low in the majority of patients (grade 2-3 neutropenia/anemia in 8/28 cases); however, two fatal infections occurred and one additional patient died because of disease progression. Extra-hematological toxicity was generally mild. This preliminary report suggests that oral combination of FLU and CY at low dose is effective as the i.v. formulation and standard doses, since it may induce rapid responses in about 90% of elderly patients with CLD, with an acceptable toxicity.
We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.
