The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)

Objective: Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by t(9;22) translocation, in which cytogenetic aberrations can occur in Ph(+) and (-) clones. These aberrations develop due to clonal evolution as well as treatment and they have prognostic significance. They are grouped as major and minor route anomalies in terms of their effects on prognostic parameters, such as treatment response, overall survival (OS), disease stage, complete cytogenetic response (CCyR), and major molecular response (MMR). It is stated that major route anomalies have unfavorable prognostic effects compared to minor route anomalies. We aimed to investigate the frequency and prognostic effects of cytogenetic anomalies detected in Ph(+) and (-) clones. Materials and Methods: In this study, we retrospectively analyzed the cytogenetic results of 450 patients diagnosed with CML between 2005 and 2020. Results: We detected cytogenetic aberrations in Ph-positive and negative clones in 41 of 450 patients. The most common anomalies were trisomy 8 (+8), additional Ph chromosome (+Ph), and loss of chromosome Y. Rarely, aneuploidy of the Y chromosome, dup (22), +11, and +6 were seen in CML patients. We observed that these identified aberrations negatively affected MMR and CCyR, and generally resulted in changing imatinib treatment for second-generation tyrosine kinase activity inhibitors. Our results are compatible with the literature. Conclusion: We suggest that cytogenetic aberrations detected in Ph(+) and (-) clones should be a warning sign in terms of treatment and require close observation. The use of cytogenetic methods for the identification of these anomalies is also important.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Conventional and molecular cytogenetic analyses in Turkish patients with multiple myeloma.

OBJECTIVE: Multiple myeloma (MM) is characterized by the accumulation and proliferation of malignant plasma cells, secreting monoclonal immunoglobulins and genetic abnormalities in MM have implications for disease progression and survival. In the present study, we investigated the frequency of chromosomal abnormalities (CA) in Turkish patients with MM, using interphase FISH and CC and evaluated the relationship between the rearrangements detected, prognosis and stage of disease. MATERIAL AND METHODS: We performed conventional cytogenetic and FISH studies in 50 patients to detect chromosome anomalies associated with MM. FISH probes were used to detect 13q14, 13q34, 17p13 deletions, IGH rearrangements, and monosomy and/or trisomy of chromosomes 5, 9, and 15. RESULTS: CC studies could be performed in 32 of 50 cases and five patients (15.6%) showed chromosomal aberrations while 27 (84.3%) had normal karyotypes. By FISH, eighteen percent (9/50) of cases were found to be normal for all parameters evaluated. Eighty-two percent (41/50) of the patients were positive for at least one abnormality. Chromosome 13 anomalies were detected in 54% (27/50) of cases. The second most common aberration observed is chromosome 15 aberrations (50%). CONCLUSION: Median survival rate was shorter in patients with one of the abnormalities including chromosome 13 aberrations, IGH rearrangements or P53 deletions. Chromosome 15 aberrations were significantly higher in patients with stage III disease (p=0.02). We conclude that FISH studies should be performed in conjunction with conventional cytogenetic analysis for prognosis in multiple myeloma patients.

Candida norvegensis fungaemia in a neutropenic patient with acute non-lymphoblastic leukaemia.

We report a case of fungaemia resulting from Candida norvegensis in a patient with acute non-lymphoblastic leukaemia-M4 from Turkey. Candida norvegensis was isolated from two different peripheral blood samples that were taken at 2-day intervals. Despite treatment with liposomal amphotericin B, the patient died of multi-organ system failure.

Treatment of autoimmune thrombocytopenia in a case of chronic hepatitis C with ursodeoxycholic acid.

Pegylated interferon (PEG-IFN) alpha and ribavirin therapy has become the standard treatment in chronic hepatitis C virus (HCH)-infected patients. While thrombocytopenia associated with IFN use is frequently observed among these patients, autoimmune thrombocytopenia is one of the rarely observed adverse effects. In the present report, we present a case with chronic HCV infection in which autoimmune thrombocytopenia developed at week 7 of PEG-IFN alpha 2b plus ribavirin therapy. The patient subsequently received ursodeoxycholic acid (UDCA) treatment. Although there is not an adequate number of studies on this subject, it was concluded that the use of UDCA in cases of autoimmune thrombocytopenia that have developed due to PEG-IFN treatment in chronic HCV infection is a favorable option.

Prognostic impact of chromosome alterations detected by FISH in Turkish patients with B-cell chronic lymphocytic leukemia.

The goal of this study was to evaluate the relation of chromosomal abnormalities detected by fluorescence in situ hybridization (FISH) in the prognosis of B-cell chronic lymphocytic leukemia (B-CLL) patients. We evaluated the common recurrent chromosomal aberrations in 79 B-CLL patients (51 men, 28 women; mean age 64.3+/-1.2) by FISH analysis using 11q22.3 (ATM), 13q14.3 (13S319 and 13S25), CEP12, and 17p13.1 (TP53) specific probes. Of the 79 patients analyzed by FISH, 40 or 50.6% had at least one aberration. In particular, 34 (43%) patients had a single abnormality and 6 (7.6%) patients had 2 abnormalities. The most frequent abnormality was 13q14.3 deletion, which was detected in 26 (32.9%) patients. Trisomy 12 was seen in 12 (15.2%) cases, and was followed by 17p13.1 (TP53) deletions and 11q22.3 (ATM) deletions in 6 (7.6%) and 4 (5.1%) patients, respectively. When the overall frequencies of these chromosomal aberrations were distributed according to RAI stages, the majority of patients with 13q14.3 deletion (55%), trisomy 12 (70%), and ATM or TP53 deletions (66.7 %) were in advanced stages of disease (RAI II-IV). The overall survival durations in good, intermediate, and poor prognostic groups were 51+/-1.3, 50.9+/-8.6, and 12+/-3.3 months, respectively. Our data suggests that FISH analysis of B-CLL patients provides important diagnostic, clinical, and prognostic information which may help clinicians assess the prognosis and make appropriate treatment decisions.

Factor V Leiden mutation and deep venous thrombosis in a patient with hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome is a rare condition characterized by extremely high peripheral blood eosinophil counts. Patients with idiopathic hypereosinophilic syndrome are at increased risk for thrombosis. The coexistence of idiopathic hypereosinophilic syndrome with other thrombotic disease is rare. We present an additional case of idiopathic hypereosinophilic syndrome and factor V Leiden mutation, which lead to deep vein thrombosis.

Autoimmune thrombocytopenia induced by PEG-IFN-alpha plus ribavirin in hepatitis C.

Mild thrombocytopenia is a common adverse effect of interferon-alpha and pegylated interferon-alpha, largely ascribed to bone marrow suppression. Nevertheless, rare cases of autoimmune thrombocytopenia following standard or pegylated interferon treatment have been reported in the literature. In this report, we have presented a patient who developed an immune-mediated thrombocytopenia during the course of therapy with pegylated interferon/ribavirin for hepatitis C virus infection. After cessation of pegylated interferon/ribavirin treatment, thrombocytopenia was treated successfully with danazol and intravenous gamma-globulin.

Acute liver failure due to Hodgkin's lymphoma.

OBJECTIVE: To describe an unusual case of acute liver failure due to Hodgkin's lymphoma. CASE PRESENTATION AND INTERVENTION: A 37-year-old man was admitted with jaundice and abdominal distension. Physical examination showed tender hepatosplenomegaly, ascites, grade I encephalopathy, left cervical (2 x 1 cm) and axillary (1 x 1 cm) lymph nodes. The laboratory data revealed elevated serum bilirubin, transaminases, lactate dehydrogenase, and coagulation defects. Initially, primary liver disease was considered, but a liver biopsy revealed infiltration of the liver by Hodgkin's lymphoma that was confirmed by lymph node biopsy. Hodgkin's lymphoma was of lymphocyte depletion type. CONCLUSION: This case demonstrates that in the presence of lymphadenopathy involving acute liver failure, hematological malignancies should be taken into consideration. Liver and lymph node biopsies should be performed as early as possible.

C-Reactive Protein in the Follow-up and Estimation of Infections in Acute Leukemic Patients.

Fifty-five febrile neutropenic episodes were monitored by C-reactive protein (CRP) in 26 patients with acute leukemia. In nonfebrile period of patients, serum CRP level was 0.89 mg/dL (range 0.1-8.8 mg/dL) while it was found to be raised to 9.57 mg/dL (range 0.5-24.1 mg/dL) in the febrile group (p= 0.0001). Serum CRP level at the onset of fever was 9.25 mg/dL (range 0.1-16.2 mg/dL) in patients in whom fever was treated succesfully with antipseudomonal beta-lactam antibiotic and aminoglycoside therapy declined to normal levels (p= 0.01); 17.0 mg/dL (range 5.2-33.5 mg/dL) in patients still persisting fever with this combined therapy and so obtained vancomycin (p= 0.001); 16.6 mg/dL (range 0-38.7 mg/dL) in patients required amphotericin B in addition (p= 0.001). In the initial febrile episode; fever resolved at day 3.3 ± 1.21 in patients with serum CRP value below 5 mg/dL; at day 4.42 ± 1.88 in patients with serum CRP value between 10-15 mg/dL; at day 5.14 ± 1.68 in patients with serum CRP value above 15 mg/dL. There was no statistical difference at the time of fever resolution among the first three groups. There was a remarkable difference between groups with CRP values below 5 mg/dL and above 15 mg/dL (p= 0.04). We conclude that determination of serum CRP level before and after infection in febrile neutropenic patients is useful for the follow-up and estimation of febrile neutropenic episode in acute leukemic patients.

Resolution of immune thrombocytopenic purpura after colectomy for ulcerative colitis.

A number of different hematologic abnormalities are often encountered in patients with ulcerative colitis. Among them, thrombocytopenia is observed mostly as a side effect of therapy. Immune thrombocytopenic purpura is rarely reported in patients with ulcerative colitis, and various treatment modalities have been used for these two disorders. We report a case with ulcerative colitis and immune thrombocytopenic purpura which were cured after the colectomy. This result suggests that immune thrombocytopenic purpura is the extraintestinal manifestation of ulcerative colitis.

Effect of spironolactone on impaired fibrinolysis of hypertensive patients.

BACKGROUND/AIMS: Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have beneficial effects on impaired fibrinolytic activity of hypertensive patients. The aim of the study was to evaluate the effect of antialdosterone treatment on impaired fibrinolysis of hypertensive patients. METHODS: Fourteen hypertensive outpatients and 14 normotensive healthy volunteers participated in this study. Blood samples for plasminogen activator inhibitor-1 (PAI-1) antigen and tissue plasminogen activator (t-PA) antigen were obtained at baseline in all patients and control subjects. Then all hypertensive patients used spironolactone 50 mg/day for a week. Blood samples were again obtained after a week of spironolactone treatment. RESULTS: The mean basal plasma level of PAI-1 of hypertensive patients was higher than those of the normotensive control group (60.98 +/- 4.2 vs. 24.09 +/- 1.61 ng/ml, p < 0.01) The mean basal t-PA level was similar in the hypertensive and control subjects (7.49 +/- 0.65 vs. 8.78 +/- 0.92 ng/ml, p > 0.05). The mean PAI-1 level decreased after a week of spironolactone treatment (60.98 +/- 4.2 vs. 42.99 +/- 7.98 ng/ml, p < 0.05). The mean plasma t-PA level of hypertensive patients increased after spironolactone treatment (7.49 +/- 0.65 vs. 11.09 +/- 1.33 ng/ml, p < 0.05). CONCLUSION: This study shows that spironolactone improves impaired fibrinolysis in systemic hypertension. It provides evidence for a direct link between aldosterone and the fibrinolytic system in humans.

Langerhans cell histiocytosis with transformation to acute leukemia showing 45,X, t(8; 21), 5q-, -Y karyotype.

A 31 -year-old man was admitted to hospital with onset of difficulty in walking and urinary incontinence, leading to the diagnosis of Langerhans cell histiocytosis (LCH) which was replacing a thoracic vertebra. Four months after the completion of radiation therapy, he was referred to our department with persistent fever and severe pyogenic ulceration mainly affecting the right-hip. A diagnosis of acute non-lymphoblastic leukemia (ANLL) was made. Cytogenetic studies showed 45,X, t(8; 21), 5q-, -Y We report this case because, development of acute leukemia after LCH is rare and the literature searched for any cytogenetic study in these kind of cases yielded no data.