Nergiz Erkut

A Case of Acute Colitis with Severe Rectal Bleeding in a Patient with Chronic Myeloid Leukemia after Dasatinib Use

matologic remission. Ten weeks after starting dasatinib treatment, the patient was admitted to our hospital with abdominal pain and rectal bleeding. Laboratory results were as follows: hemoglobin 10.3 g/dl, white blood cells 6 ! 10 9 /l, platelets 185 ! 10 9 /l, prothrombin time 14 s, active partial thromboplastin time 33.3 s, international normalized ratio 1.25. Stool examination was negative for parasites and other pathogenic bacteria. Sigmoidoscopic examination was performed with only rectal osmotic laxative without entire colon cleansing. There was no active bleeding, but multiple milimetric nodular hyperemic lesions on the mucosa were seen in the left side of colon and biopsies were taken during sigmoidoscopic examination ( fig. 1 ). Histopathological findings revealed nonspecific active colitis ( fig. 2 ). The patient was hospitalized and dasatinib treatment was stopped. No bleeding was observed during follow-up and colonoscopy was performed 2 weeks later. Endoscopic and histopathological findings were all normal, and dasatinib treatment was restarted. The patient was admitted to the hospital again with hematochezia 1 month after dasatinib administration. Colonoscopy repeated and findings were consistent with acute colitis. Again dasatinib treatment was stopped and patient was observed for 5 days in hospital without any bleeding. Repeated colonoscopy was normal after dasatinib treatment discontinuation. Nilotinib (400 mg/day) was started as an alternative to dasatinib for CML treatment. The patient remained in hematological remission during 6 months of follow-up without any further complication. Dasatinib is a second-line tyrosine kinase inhibitor used in imatinib resistant or intolerant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. It inhibits several critical oncogenic proteins, including bcr-abl, Src familial kinase, Kit, platelet-derived growth factor receptor and ephrin A receptor kinase. Dasatinib, which binds both active and inactive conformation of bcr-abl oncoprotein, has greater potency than imatinib for both wild-type and mutant BCR-ABL, except the T315I mutation [1, 2] . Mild to moderate thrombocytopenia and neutropenia occurred in approximately 50% of patients, but it is generally well tolerated. Other side effects are diarrhea, headache, weakness, pleural effusion, nausea and peripheral edema. Gastrointestinal bleeding may occur in up to 7% of patients using dasatinib [3] . Current literature suggests severe rectal bleeding due to acute colitis during dasatinib treatment has been reported only in 1 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia patient [4] . Here, we report an adult case with acute colitis with severe rectal bleeding after dasatinib use. This complication has not been previously reported in an adult population. A 55-year-old patient had been diagnosed with blastic phase of CML 2 years ago. After remission induction treatment including cytosine arabinoside, idarubicin and imatinib (400 mg/day), maintenance treatment was continued with imatinib. During the follow-up, dasatinib (100 mg/day) was started because of disappearance of heReceived: December 14, 2009 Accepted after revision: January 28, 2010 Published online: April 8, 2010

The use of Ankaferd blood stopper in a patient with Glanzmannʼs thrombasthenia with gingival bleeding

The Journal of Blood Coagulation and Fibrinolysis has printed an article comparing the efficacy of Ankaferd Blood Stopper (ABS; Ankaferd Drug, Inc., Istanbul, Turkey) in antithrombotic drug-induced primary and secondary hemostatic abnormalities of a rat-bleeding model [1]. ABS is a folkloric medicinal plant extract that has been used in Turkey traditionally for hemostasis. The use of topical ABS has been approved in the management of dental surgery and external hemorrhage by the Ministry of Health in Turkey. Glanzmann’s thrombasthenia, a life-threatening bleeding disorder, is an inherited platelet function disorder characterized by a severe reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists due to abnormalities of platelet glycoprotein (GP) GPIIb and/or GPIIIa receptors. Bone marrow transplantation (BMT) is the only potentially curative treatment for Glanzmann’s thrombasthenia, in which platelet transfusion is considered a standard therapy for securing hemostasis in individuals with Glanzmann’s thrombasthenia, when the local measures and antifibrinolytic agents are inadequate. Recombinant activated factor VII (rFVIIa) is used for treating severe bleeding in patients with isoantibodies [2]. We report the use of ABS in a type II Glanzmann’s thrombasthenia patient with gingival bleeding due to periodontal therapy. A 24year-old man with Glanzmann’s thrombasthenia underwent periodontal treatment (scaling and root planning) in our university because of frequently recurrent bleeding secondary to early periodontitis. Physical examination revealed no abnormalities. Routine laboratory investigations revealed normal hemoglobin, platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and bleeding time performed by the Ivy method was 15 min (normal 2–9 min). The platelet aggregation test presented no agglutination with epinephrine, ADP, and collagen. Periodontal treatments were performed resulting minor gingival bleeding with no need for erythrocyte transfusion (Fig. 1). ABS was

Treatment related changes in antifibrinolytic activity in patients with polycythemia vera

Abstract Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.

Relation of HLA-A, -B, -DRB1 Alleles and Haplotypes in Patients with Acute Leukemia: A Case Control Study

BACKGROUND AND AIMS A relationship between acute leukemia and HLA alleles has been demonstrated in several studies. However, the frequencies of HLA class I (A, B) and class II (DRB1) alleles and haplotypes has not already been determined in Turkish patients with acute leukemia. METHODS We investigated the relation of the HLA alleles and haplotypes in 237 adult acute leukemia patients [103 acute lymphoblastic leukemia (ALL), 134 acute myeloid leukemia, (AML)] and 360 unrelated normal subjects by PCR-SSOP method using Luminex technology. RESULTS Allele frequencies of HLA-A*03, and B*51 were higher in patients with AML compared with the controls (p = 0.019, and p = 0.001; respectively). Furthermore, HLA-A*11 and DRB1*01 allele frequencies were determined to be higher in patients with ALL (p = 0.01, p = 0.001; respectively), whereas DRB1*13 allele frequencies lower than controls (p = 0.003). The most observed haplotypes A*03 B*51 DRB1*11 (3.73 vs. 0%) in patients with AML; A*02 B*35 DRB1*01 (2.91 vs. 0%) and A*02 B*51 DRB1*11 (2.91 vs. 1.96%) in patients with ALL were determined. On the contrary, the most observed haplotype was A*02 B*35 DRB1*13 (2.19%) in the controls. We found A*02 B*39 DRB1*16 haplotype negatively associated with AML, whereas A*02 B*35 DRB1*13 was in ALL (p = 0.015, and p = 0.017; respectively). CONCLUSIONS These results suggest that HLA-A*03 and B*51 alleles may play a presumptive predisposing factor in AML. In addition, HLA-A*11 and DRB*01 alleles have been found to be associated with ALL, whereas DRB1*13 allele was determined to be negatively associated.

Effect of LMO2 protein expression on survival in chronic myeloid leukemia patients treated with imatinib mesylate.

Abstract LIM domain only-2 (LMO2) is an important regulator of hematopoietic stem cell development. LMO2 protein is expressed in all three hematopoietic lineages precursors of the hematopoietic system, and its expression has been shown to decrease gradually during differentiation. Chronic myeloid leukemia (CML) is a malignant clonal myeloproliferative disorder in which the terminal differentiation is not altered until the appearance of an accelerated or blast phase. We examined whether LMO2 protein expression can predict outcome CML patients undergoing tyrosine kinase inhibitor therapy, imatinib mesylate (IM). Immunohistochemistry on bone marrow biopsy material for LMO2 protein was performed in 47 CML patients. We report that the LMO2 protein expression is correlated with improved hematologic remission and overall survival in the CML patients treated with IM. The immunohistologic analysis of LMO2 protein expression may become a predictive factor for anticipating the treatment responses of CML patients.

Multiple myeloma with multilobated plasma cell nuclei.

Address for Correspondence: Dr. Mehmet Sonmez, Department of Haematology, School of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey Phone: +90 462 377 58 48 Fax: +90 462 328 07 04 E-mail: mesonmez@yahoo.com doi:10.5152/tjh.2011.38 A 61-year-old male patient was admitted to our hospital with backache and fatigue. Physical examination was normal, except for pallor. Laboratory results at initial evaluation were as follows: hemoglobin: 105 g L; hematocrit: 0.31%; white blood cell (WBC) count: 6.3x109 L; platelet count: 200x109 L; blood urea nitrogen (BUN): 22.1 mmol L; creatinine: 477.3 μmol L; calcium: 2.8 mmol L; total protein: 74 g L; albumin: 43 g L; erythrocyte sedimentation rate (ESR): 44 mm h-1. A monoclonal spike was present on protein electrophoresis. Protein studies (by nephelometry) showed a kappa light chain of 5.97 g L (reference range: 1.7-3.7 g L) and low levels of IgG, IgM, and IgA (8.84 g L, 0.30 g L, 0.53 g L, respectively). Beta 2 microglobulin was 1.2 mg dL (reference range: 0.07-0.19 mg dL). Urine immunoelectrophoresis showed that the patient had a kappa monoclonal light chain. Bone X-rays showed multiple osteolytic lesions. The bone marrow aspirate and biopsy specimen morphology showed infiltration by atypical and multilobated plasma cell nuclei (Figures 1 and 2). The bone marrow biopsy specimen stained positive with CD138 (Figure 3). Multiple myeloma with multinucleated plasma cells is a rare morphological variant, which usually presents with light chain expression, and is characFigure 1. Atypical and multinucleated plasma cell infiltration in bone marrow aspirate

Can ischemia-modified albumin be a valuable indicator of tissue ischemia in polycythemia vera?

Abstract The red cell expansion in polycythemia vera (PV) causes hyperviscosity affecting blood flow, which plays a major role in the pathogenesis of both microcirculatory disturbances and ultimately thromboses. Ischemia-modified albumin (IMA) is produced during an ischemic states and is present in blood in early and easily detectable levels. This study investigated whether IMA is a useful adjunct in the determination of ischemia in patients with PV, prior to them exhibiting clinical evidence of thrombotic complications. Blood IMA levels were determined in 20 PV patients and in 20 healthy individuals using a method described by Bar-Or. Mean IMA levels in the PV group were significantly higher than those of the control group (P<0·05). At the optimum cutoff point (0·193 absorbance units), the sensitivity and specificity of IMA were 80 and 100% to ischemia, respectively. In conclusion, IMA may be a valuable biochemical marker in predicting tissue ischemia in PV before the signs of vascular disturbances occur.

The indicator of hypoxia in acute leukemia: Ischemia-modified albumin.

BACKGROUND Hypoxia plays an important role in the development and progression of hematologic malignancies. OBJECTIVE This study was intended to investigate the effectiveness of ischemia-modified albumin (IMA) for demonstrating hypoxia in patients with acute leukemia. METHODS Blood specimens were collected from 132 subjects (44 acute leukemia patients, 40 iron deficiency anemia (IDA) patients and 48 healthy controls). Serum levels of IMA and malondialdehyde (MDA) were analyzed using conventional methods. RESULTS Serum levels of IMA were higher in patients with acute leukemia than in those with IDA and healthy controls (acute leukemia patients; 0.69 ± 0.14 ABSUs, IDA patients; 0.61 ± 0.09 ABSUs, controls; 0.50 ± 0.09 ABSUs, respectively). There was a negative correlation between serum IMA levels and hemoglobin (Hb) values (r = - 0.312) and between serum IMA levels and hematocrit (Hct) values, (r = - 0.305) in patients with acute leukemia. Serum levels of MDA were higher in patients with acute leukemia than in those with IDA. But there was no difference in patients with acute leukemia and IDA compared to healthy controls (acute leukemia patients; 2.23 ± 1.82 nmol/mL, IDA patients; 1.36 ± 0.94 nmol/mL, healthy controls; 1.79 ± 0.78 nmol/mL, respectively). CONCLUSIONS IMA can be effective for demonstrating hypoxia in patients with acute leukemia.

Autoantibodies against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA) I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML) and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively). A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001). Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

Comparison between Hyper-CVAD and PETHEMA ALL-93 in Adult Acute Lymphoblastic Leukemia: A Single-Center Study

Background: Although cure rates in pediatric acute lymphoblastic leukemia (ALL) are quite high with combined chemotherapy regimens, complete response (CR) and long-term survival rates in adults are 80–90 and 30–40%, respectively. Currently, combined chemotherapy regimens, such as Hyper-CVAD and PETHEMA, are used in patients with adult ALL. However, there has been no study comparing the results of Hyper-CVAD and PETHEMA ALL-93. Methods: In this retrospective single-center study, we evaluated the results of Hyper-CVAD and PETHEMA ALL-93 in 51 ALL patients treated between September 2008 and March 2017 at the Department of Hematology, Faculty of Medicine, Karadeniz Technical University. Results: Thirty-eight patients were treated with Hyper-CVAD and 13 with PETHEMA ALL-93. CR was obtained in 90 and 100% of patients, respectively. Survival estimates were comparable between Hyper-CVAD and PETHEMA ALL-93, with a median overall survival (OS) and a median disease-free survival (DFS) of 17.5 and 12.1 months, respectively, for Hyper-CVAD and of 18.6 and 12.9 months, respectively, for PETHEMA ALL-93. The 2-year OS rates for Hyper-CVAD and PETHEMA ALL-93 were 30 and 40%, respectively, and the 2-year DFS rates were 28 and 44%, respectively. PETHEMA ALL-93 resulted in more hepatotoxicity, hypofibrinogenemia, aspergillus infection, and skin rash than Hyper-CVAD. Conclusions: Although Hyper-CVAD and PETHEMA ALL-93 showed similar effects, Hyper-CVAD was tolerated better. Age and comorbidities should be taken into account before a chemotherapy regimen is determined for patients with ALL.