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Hydroxyurea treatment for chronic myeloid leukemia during pregnancy

The incidence of chronic myeloid leukemia (CML) associated with pregnancy is estimated to be 1/75,000. Several types of treatments have been used for CML during pregnancy. These are cytotoxic drugs, alpha-interferone, splenic irradiation (with shielding of the uterus) and leukapheresis. Hydroxyurea is a cytotoxic drug that inhibits the synthesis of DNA and can be used both in the chronic and accelerated phases of CML (1). We present a woman with CML who has successfully given birth to a live baby after treatment with hydroxyurea.

Coexistence of chronic neutrophilic leukemia with light chain myeloma

A 60-year-old woman who presented with weakness, night sweats, bone pain, easy bruising and weight loss was found to have ecchymoses and hepatosplenomegaly. Blood counts showed persistent neutrophilia of mature cell type with Döhle bodies and toxic granulation. Coexistence of chronic neutrophilic leukemia and multiple myeloma of kappa light chain type was documented by bone marrow examination and immunofixation.

Plasma levels of free tissue factor pathway inhibitor in patients with various thyroid disorders

Various coagulation abnormalities occur in thyroid disorders and its range may vary from subclinical laboratory abnormalities to clinically significant disorders of coagulation. Tissue factor pathway inhibitor (TFPI), which inhibits the initial reaction of tissue factor mediated coagulation pathway, is reported to be increased in patients with Graves disease (GD) in one study. Hyperthyroid (n=10), hypothyroid (n=10) and subclinical hypothyroid (n=10) patients and control cases (n=16) were evaluated for free and total tissue factor pathway inhibitor (tTFPI), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) levels in disease and euthyroid states. Free TFPI levels were significantly higher in hyperthyroid patients compared with the control group and subclinic hypothyroid patients (p<0.001), but not with hypothyroid patients (p>0.05). After the euthyroid state was obtained in the hyperthyroid group, the levels of total TFPI (p<0.05), free TFPI (fTFPI) (p<0.005), t-PA (p<0.005) and PAI-1 (p<0.02) decreased significantly. In hyperthyroid patients, there was a strong correlation between thyroid functions and free TFPI levels. In conclusion, we hypothesize that coagulation abnormalities seen in thyroid disorders cannot be explained directly with the impaired fibrinolytic activity but also with the elevated fTFPI levels. Both increased plasma fTFPI and PAI-1 levels could be markers of the peripheral activity of thyroid hormones.

Prognostic significance of immunohistochemical classification of diffuse large B-cell lymphoma

Abstract Aim: To evaluate the clinical significance of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups, we analysed 50 DLBCL cases using immunohistochemical methods. Methods and results: Fifty DLBCL patients were evaluated retrospectively. The expression of CD10 was associated with better OS (p=0·04) whereas expression of mum-1 was associated with worse OS (p=0·009). There were no significance of OS in case of expression of bcl-6 (p=0·05) and bcl-2 (p=0·3). They were subclassified using CD10, mum-1, bcl-6 as germinal center B-cell like (GCB) lymphoma (30%) and non-GCB lymphoma (70%). The OS and EFS (event free survival) were longer in GCB group (p=0·002) and 5-year OS for GCB group was 92% compared with only 44% for the non-GCB group (p=0·02). The OS of the GCB group also was longer compared to that of the non-GCB group in low IPI subgroup (p=0·01). Conclusion: The existance of survival differences between GCB a non-GCB group also in the patients with low IPI score, showed the importance of prognostic classification in the risk-adaptive treatment approaches. The classification as GCB and non-GCB based immunostains may enable to define more accurate prognostic groups in DLBCL.

Flow Cytometric Analysis of Circadian Changes in Platelet Activation Using Anti-Gmp-140 Monoclonal Antibody

The hemostatic activity of blood shows a circadian variation with a higher frequency of acute coronary events in the morning. The thrombotic tendency of blood is influenced by many factors, including platelets. Diurnal changes of in vivo platelet activation were investigated by whole blood flow cytometry in 10 young healthy male volunteers using anti-GMP-140 (anti-alpha-granule membrane protein 140 kD) monoclonal antibody at 3h intervals from 06:00 to 24:00. We also studied circulating platelet aggregates to investigate whether there exists a similarity between the results of these methods. Results of flow cytometric analysis indicate that there is an increase in platelet activation during the period from 06:00 to 09:00. Platelet activation then decreases gradually during the period from noon to midnight. These changes are accompanied by a similar trend in circulating platelet aggregates. This suggests that GMP-140 expression on platelets is synchronized with or followed by platelet aggregate formation in vivo, and increased platelet activation may predispose individuals to thrombosis at this time.

Consistent Loss of Heterozygosity at 14q32 in Lymphoid Blast Crisis of Chronic Myeloid Leukemia

Little is understood about the basic biological mechanisms that underlie the reasons for acute transformation in chronic myeloid leukemia (CML). Progression of disease may include inactivation of one or more tumor suppressor genes (TSGs). A widely used methodology for indirectly detecting somatic inactivation of TSGs is searching loss of heterozygosity (LOH) for polymorphic loci located in or near the gene(s) of interest. We aimed to analyze DNA of chronic phase and blastic phase archive material of 15 CML patients for LOH using D1S430, D2S123, D3S1611, D11S29, D14S65, D17S520, BAT 40 markers, the dinucleotide repeat located in the ABL gene and the trinucleotide repeat located in the BCR gene (amplification of the trinucleotide in the BCR gene could not be succeeded). LOH was identified by a %50 lost of one of the alleles intensity. LOH was detected with the ABL dinucletide repeat and D2S123 marker in two patients and with the D14S65 marker in three patients. The three patients exhibiting LOH at the D14S6S locus, all proceeded through lymphoid blast crisis. The D14S65 marker is located at the 14q32 locus which contains the immunglobulin heavy chain gene and the TCL1 oncogene. 14q32 abnormalities at the molecular level, may be predictive for lymphoid blast crisis, whether or not they are detectable cytogenetically

Platelet activation in congenital heart diseases

The research presented here investigated platelet activation in cyanotic and acyanotic congenital heart diseases (CHD). Children with cyanotic CHD are prone to both thrombosis and hemorrhage. However, patients with acyanotic CHD may also have a mild bleeding disorder. The platelet activation in CHD was investigated in support of a hypothesis that platelet activation may play a role in the hemostatic abnormalities reported in these patients. Platelet activation was determined by using flow cytometry with anti‐CD62 monoclonal antibody (mAb), which has been shown to be a specific marker of platelet activation. Thirteen children with cyanotic CHD, 33 children with acyanotic CHD and 17 healthy children serving as controls were studied. Platelet activation was significantly higher in the cyanotic group and also in the acyanotic group compared with the healthy children (P = 0.0000 and P = 0.019, respectively). In the cyanotic group, platelet activation showed a direct correlation with arterial O2 saturation (SaO2) (P = 0.014). There was no correlation between platelet activation and erythrocyte related parameters in either group. Platelet activation occurs in CHD, particularly in patients with cyanotic CHD (even in patients with no evidence of clinical thrombosis) and it may play a role in the pathogenesis of thrombotic disorders seen in these patients.

Hemophagocytic syndrome associated with inappropiate secretion of antidiuretic hormone in lymphoma and acute myeloblastic leukemia: Report of two cases

Hemophagocytic syndrome (HPS) is a rare clinicopathological disorder characterized by systemic proliferation of phagocytizing histiocytes associated with fever, cytopenias, lymphadenopathy, hepatosplenomegaly, and disseminated intravascular coagulopathy. We present the association of hemophagocytic syndrome associated with inappropriate secretion of antidiuretic hormone (SIADH) in two cases of hematological malignancies; anaplastic large cell lymphoma (ALCL) and acute myeloblastic leukemia (AML M4) In the patient with lymphoma, the diagnosis of lymphoma, HPS and SIADH were concurrent. In the patient with AML, HPS and SIADH were observed while the patient was in hematological remission. Thus it seems that patients with HPS may also carry a risk for the development of SIADH; the relationship with HPS and SIADH should be further investigated.

Platelet Activation during the Early Neonatal Period

The first week of life is a time when hereditary or more frequently acquired factors lead to some important differences in the hemostatic mechanism of the newborn. It has been well known that ill neonates are prone to both hemorrhage and thrombosis. The aim of this study was to answer the question of whether there is a difference in platelet activation in healthy neonates during the first days of life that may contribute to both hemorrhage and thrombosis in the presence of additional pathologic insults. Platelet activation was determined with flow cytometry using monoclonal antibodies in 63 healthy children (29 neonates, 17 infants, and 17 older children). There was no significant difference in platelet activation among these three age groups (p > 0.05). In addition, platelet activation did not show any significant relationship to age, sex, mode of delivery, or blood bilirubin concentration (p > 0.05). It has been previously reported that platelet activation occurs at the time of birth. We could not find any evidence that healthy newborns during the first 3 days of life exhibit increased platelet activation. Further studies on platelet activation in ill neonates will help to clarify whether platelet activation plays a role in the pathogenesis of thrombotic and/or hemorrhagic disorders.

Gingival involvement in a patient with CD56+ chronic myelomonocytic leukemia

Leukemic infiltration of the gingiva is most commonly reported to be associated with monocytic subtypes of acute myeloblastic leukemia (AML) but rarely with myelodysplastic syndromes (MDS). Here we report a case of CD56 +  chronic myelomonocytic leukemia (CMML) who developed gingival involvement simultaneously when the leukocyte count elevated. At that time no increase in peripheral or bone marrow blasts were observed. Gingival hypertrophy regressed with the treatment of hydroxyurea. Three months later, bone marrow blast count elevated and the patient was treated with two courses of AML-like regimen and then one course of consolidation therapy. The patient is in complete hematological remission for one and a half years. Similar to other extramedullary involvements, gingival hypertrophy in CMML can be a harbinger of the disease entering a more aggressive phase requiring systemic chemotherapy.