Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients.

Objective: In this study, we investigated the effects of calreticulin (CALR) and JAK2V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET). Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR- and JAK2V617F-mutated ET patients were evaluated retrospectively. Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2V617F- and CALR-positive, respectively. CALR-mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x109/L vs. 709x109/L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2V617F- and CALR-mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2V617F- and CALR-mutated patients. Thrombosis-free survival (TFS) was superior in CALR-mutated patients compared to JAK2V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs. Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2V617F and were associated with younger age at diagnosis. JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

The evaluation of small fibers in multiple sclerosis.

BACKGROUND: Dysesthetic or ongoing extremity pain is a common symptom in all multiple sclerosis (MS) types. Although the pathology of the disease is the demyelination of central neurons, the patients may also complain of neuropathic pain in distal extremities that is generally related to A-delta and C fiber dysfunction. It is not known whether thinly myelinated and unmyelinated fibers are affected in MS patients. We aim to investigate the small fiber loss and its length dependency. METHODS: We evaluated the skin biopsy taken from proximal and distal leg of MS patients with neuropathic pain. Six patients with primary progressive MS (PPMS), seven with relapsing-remitting MS (RRMS), seven with secondary progressive MS (SPMS) and as a control group ten age and sex-matched healthy controls were included. Neurological examination, electrophysiological evaluation and DN4 questionnaire were performed. Subsequently, skin punch biopsy from 10 cm above the lateral malleolus and proximal thigh were done. The biopsy samples were stained with PGP9.5 antibody and intraepidermal nerve fiber density (IENFD) was determined. RESULTS: The mean proximal IENFD was 8.58±3.58 fibers/mm among MS patients and 14.72±2.89 fiber/mm among healthy controls (p=0.001). However, the mean distal IENFD did not differ between MS patients and healthy controls (9.26±3.24 and 9.75±1.6 fiber/mm respectively. Although proximal and distal IENFD tends to be lower in MS patients with neuropathic pain, there was no statistically significant difference between MS patients with and without neuropathic pain CONCLUSION: Although MS is a demyelinating disease, unmyelinated fibers can also be affected. Our findings suggest non-length dependent small fiber neuropathy in MS patients.

An acute transverse myelitis attack after autologous stem cell transplantation: A rare case.

Transverse myelitis is a quite rare complication of hematopoietic stem cell transplantation. The case is here reported of a 49 year old male with diffuse large B cell lymphoma in complete remission who developed transverse myelitis after autologous stem cell transplantation. The patient presented with numbness and sensory loss of the bilateral lower extremities and difficulty in urinating on the 20th day after cell transplantation. Millimetric hyperintensity was detected in the C5-C6 and T2-T5 segments of the spinal cord on cervical and thoracic vertebral magnetic resonance imaging. Treatment was initiated of pulse steroid and intravenous immunoglubulin followed by plasmapheresis and cyclophosphamide due to inadequate response. The patient then started a rehabilitation program and was discharged in the 9th month after stem cell transplantation when most of the symptoms were relieved. To the best of our knowledge, this is the first case reported in literature of TM development after autologous stem cell transplantation.

Extramedullary relapses of acute leukemias after allogeneic hematopoietic stem cell transplantation: clinical features, cumulative incidence, and risk factors.

The aim of this study was to evaluate extramedullary (EM) relapses and its features in an allogeneic hematopoietic stem cell transplantation (alloHSCT) cohort, which consisted of patients with acute leukemia and advanced-phase chronic myeloid leukemia. One hundred and twenty-eight alloHSCT patients transplanted between the years 2001 and 2014 were analyzed. EM relapses observed in acute lymphoblastic leukemia (ALL) were more frequent than that of in acute myeloid leukemia (AML) and CML, although calculation of cumulative risk incidence, BM relapse, EM relapse, and non-relapse mortality were considered as competing risks of each other. At the 60th month, estimated CBMR and CEMR incidences were, respectively, 14.3 (5.1)% and 25.9 (6.6)% in ALL, 25.8 (5.9)% and 15.5 (4.8)% in AML, and 61.5 (16.5)% and 17.9 (13.4)% in CML. Among multiple parameters, the only type of conditioning regimen (p:0.046), EM involvement at diagnosis (p:0.009), and the presence of GVHD were found to be associated with EM relapse risk independently (p:0.045). Chronic GVHD and TBI-based regimens significantly decreased the EM relapse risk, whereas it was higher with Mel/Flu and its variants. In conclusion, EM relapse is not uncommon after alloHSCT. GVHD and TBI-based regimens may prevent this complication.

Immunosuppression-associated posterior reversible encephalopathy syndrome in an acute leukemia case.

Posterior reversible encephalopathy syndrome (PRES) was described in 1996. Herein, we aimed to report an immunosuppression- related PRES case. A 34-year-old woman was diagnosed as t-cell acute lymphoblastic leukemia and allogeneic hematopoietic stem cell transplantation (HSCT) was performed. Cyclosporine was given for GVHD prophylaxis in addition to the other routine medications of HSCT. She was hospitalized for acute renal failure and due to the possible contribution of acute renal failure cyclosporine was stopped. Tacrolimus was started for GVHD prophylaxis at a dose of 1 mg/day. However, fifteen days after the initiation of tacrolimus, blurred vision occurred in our patient. Petechial bleeding sites were detected in bilateral cerebral and cerebellar hemisphere by MR imaging. Tacrolimus dosage was reduced to 0.5 mg/day. She had hypertension which was difficult to control and followed-up in the intensive care unit. She had seizures. Control cranial MR resulted as diffusion limitation in bilateral cerebellar hemisphere, bilateral occipital and frontal-parietal regions with vasogenic edema findings; contrast involvement in left frontal-parietal and right cerebellar regions. She had vision loss and lethargy. Control cranial MR favored PRES syndrome secondary to immunosuppression. Hypertensive state was taken under control with antihypertensive treatment and all immunosuppressive agents were stopped. Two weeks later her clinical condition was slightly improved. MR test which was conducted 2 weeks after the diagnosis revealed the regression of PRES lesions. The characteristic signs on neuroimaging are the symmetrical white matter edema in the posterior cerebral hemispheres, particularly the parietal- occipital regions. In conclusion, PRES rarely develops secondary to the immunosuppressive agents and the clinicians should suspect and promptly diagnose PRES which might cause otherwise serious irreversible clinical complications.

Infections in patients with lymphoma: An analysis of incidence, relationship and risk factors.

INTRODUCTION: Bacterial infections and febrile neutropenia (FN) are major causes of morbidity and mortality in patients with hematological malignancy. The aim of this study was to investigate the incidence and risk factors of infections in lymphoma patients. METHODOLOGY: This retrospective study was conducted on 200 lymphoma patients diagnosed and treated between January 2009 and December 2017 in Diskapi Yildirim Beyazit Training and Research Hospital, a tertiary referral hospital in Ankara, Turkey. RESULTS: The mean follow-up period was 20.09 ± 19.81 months. The incidence of infection episode (IE) was 32.5% (65/200) and FN was 18.5% (37/200). Analysis of the data revealed that patients with IE had significantly higher rates of diagnosis of primary central nervous system lymphoma (PCNSL), lower baseline hemoglobin, lower baseline hematocrit, higher baseline lactate dehydrogenase levels, higher usage of central cathater, and a higher number of chemotherapy lines compared to patients with no IE. In logistic regression analysis, disease subtype of PCNSL, usage of central catheter and lactate deyhydrogenase (LDH) were found to increase the risk of infection. The odds ratio for PCNSL was 37.866 (p = 0.003), 2.679 for central catheter (p = 0.008) and 1.001 for LDH (p = 0.011). CONCLUSIONS: The risk of infection in patients with lymphoma was associated with central catheter usage, higher LDH levels and a diagnosis of PCNSL. Baseline hematological parameters were not determined to have any impact on the occurrence of infection. Patients with these risk factors should be monitored more carefully and the maximum level of infection prevention should be taken.

Growth inhibitory activity of Ankaferd hemostat on primary melanoma cells and cell lines.

OBJECTIVE: Ankaferd hemostat is the first topical hemostatic agent about the red blood cell-fibrinogen relations tested in the clinical trials. Ankaferd hemostat consists of standardized plant extracts including Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica, and Vitis vinifera. The aim of this study was to determine the effect of Ankaferd hemostat on viability of melanoma cell lines. METHODS: Dissimilar melanoma cell lines and primary cells were used in this study. These cells were treated with different concentrations of Ankaferd hemostat to assess the impact of different dosages of the drug. All cells treated with different concentrations were incubated for different time intervals. After the data had been obtained, one-tailed T-test was used to determine whether the Ankaferd hemostat would have any significant inhibitory impact on cell growth. RESULTS: We demonstrated in this study that cells treated with Ankaferd hemostat showed a significant decrease in cell viability compared to control groups. The cells showed different resistances against Ankaferd hemostat which depended on the dosage applied and the time treated cells had been incubated. We also demonstrated an inverse relationship between the concentration of the drug and the incubation time on one hand and the viability of the cells on the other hand, that is, increasing the concentration of the drug and the incubation time had a negative impact on cell viability. CONCLUSION: The findings in our study contribute to our knowledge about the anticancer impact of Ankaferd hemostat on different melanoma cells.

Treatment of pyoderma gangrenosum with thalidomide in a myelodysplastic syndrome case.

Thalidomide may be used as a treatment option for pyoderma gangrenosum (PG) and myelodysplastic syndrome (MDS). Herein, we aimed to report a patient who was treated well with thalidomide and whose diagnosis was PG with MDS. A 61-year-old man with painless ecchymotic lesions in his right upper extremity was admitted to the hospital in Isparta, Turkey, in January 2015. The lesions were diagnosed as PG. In his anamnesis, it was found that he was diagnosed with MDS 6 years ago and had been treated with cyclosporine at 2×100 mg for 5 years, which was stopped in January 2015. Aspiration from liver lesion revealed the presence of Mycobacterium tuberculosis, so antituberculosis treatment was started. Bone marrow investigation revealed MDS-refractory anemia with excess blasts (7%). For lesions in bilateral upper extremities, thalidomide treatment was started at 50 mg/d. After 1 month from the initiation of thalidomide treatment, the lesions in upper extremities had disappeared. In the literature, there are some reports of patients with PG who were successfully treated with thalidomide. Our patient is a complicated case who simultaneously has MDS, PG, and tuberculosis infection. The reason for thalidomide usage in our patient was the need of immune modulation without immune suppression. Our patient has tolerated the drug well, and excellent response was obtained after 1 month of initiation of thalidomide treatment. To conclude, thalidomide is a very effective drug acting as an immune modulator, which is useful in the clinical management of both MDS and PG.

The Prognosis of Adult Burkitt's Cell Leukemia in Real-Life Clinical Practice.

OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. MATERIALS AND METHODS: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups. RESULTS: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients. CONCLUSION: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.

OBJECTIVE: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. MATERIALS AND METHODS: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. RESULTS: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. CONCLUSION: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

Clinical associations, biological risk factors and outcomes of cerebral venous sinus thrombosis.

Objective Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease affecting young adults. The majority of the patients are female. The aim of this study is to assess the clinical associations, risk factors and outcomes of the patients with CVST. Methods The data of 75 patients with CVST admitted to our hospital between 2006 and 2016 were reviewed. Demographic and clinical features and the thrombophilic risk factors of the patients were recorded. The localizations of the thrombi were determined and modified Rankin score at the time of onset and discharge were calculated. Results The majority of our patients (78.7%) were female. Median age was 35 years (16-76). The most common symptom was headache (86.7%). In 82.6% of our patients, inherited or acquired risk factors for thrombosis were detected. Transverse sinus was the most common site of thrombosis followed by sigmoid and superior sagittal sinuses. Two thirds of the patients had involvement of multiple sinuses. The patients with the involvement of sagittal sinus had better disability at the time of admittance ( p = 0.013) while the number of involved sinuses was correlated worse disability ( p = 0.015). The neurologic states in the majority of the patients were improved by the end of the hospitalization period ( p = 0.001). There was no significant difference in disability score at discharge between men and women ( p = 0.080). No patient with CVST died in the hospitalization period. Conclusions This study is one of the largest cohort studies on CVST in our region. The results of the study disclosed that CVST had wide range of clinical manifestations and non-specific symptoms at the beginning. For that reason, in especially high risk groups for thrombosis, the diagnosis of CVST should be kept in mind.

Late Onset and Protracted Course of Steroid Refractory Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) is one of the most important causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). Occurring in 30% to 70% of patients, cGVHD has a median time to onset of 4 to 6 months and most cases present within 2 years after aHSCT. Here, we present a patient transplanted at the age of 55 who developed refractory cutaneous cGVHD more than 5.5 years after aHSCT.

Rational diagnoses of diabetes: the comparison of 1,5-anhydroglucitol with other glycemic markers.

Diabetes mellitus (DM) is a frequently encountered disease with important morbidity and mortality. The aim of this study is to document the importance of 1,5-anhydroglucitol (1,5-AG) for the diagnosis of prediabetes and DM, as well as to compare the 1,5-AG with other glycemic markers in order to understand which one is the better diagnostic tool. Between April 2012 and December 2012, 128 participants enrolled in the study. Participants were split into five groups that are IFG, IGT, IFG+IGT, diabetic and control groups by their OGTT results. The diagnostic value of markers was compared by ROC (receiver operating characteristic) method. The mean serum 1,5-AG levels in the diabetic group (33.38 nmol/ml) were lower than, IFG (59.83 nmol/ml), IGT (54.44 nmol/ml), IFG+IGT (51.98 nmol/ml) and control groups (73.24 nmol/ml). When analyzed in the total study population serum 1,5-AG levels did not differ by gender significantly. When analyzed in the total study population, 1,5-AG correlates inversely with age significantly (p = 0.036). In subgroup analysis, in the control group, serum 1,5-AG level was also inversely correlated with age (p = 0.087). The best marker for the diagnosis of prediabetes and DM was fasting plasma glucose (FPG). 1,5-AG was not found to be effective for the diagnosis of DM. This study, contributes to our knowledge of the efficiency and cut-off values of 1,5-AG for the diagnosis of prediabetes and DM. In future, there is a need for larger studies with more standardized and commonly used measurement methods for 1,5-AG, in order to evaluate the efficiency of 1,5-AG for the diagnosis of prediabetes and DM.

Common variable immune deficiency associated Hodgkin's lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report.

Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin's lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26×17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 µg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes for our patient inability to control his EBV infection which eventually lead to hemophagocytic lymphohistiocytosis. To conclude, rare simultaneous manifestation of primary immune deficiencies (PID), Hodgkin's lymphoma and EBV-HLH occurred in our patient which have concordant immunological mechanism that eventually lead poor prognosis in our patient.

A T-cell prolymphocytic leukemia case with central nervous system involvement.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive mature T cell neoplasm that typically involves peripheral blood, bone marrow, lymph nodes and spleen. It is a rare disease that comprises 2-5% of mature lymphocytic leukemia in adults. Here we present a T-PLL patient with CNS involvement. A 74-year-old man admitted to a hospital in April 2014 with vomiting. He was diagnosed as chronic lymphocytic leukemia (CLL) and R-CVP (Rituximab, cyclophosphamide, vincristine and prednisolone) chemotherapy protocol was started. After the first two cycles of chemotherapy, the patient's mental functions improved. However after the 3(rd) cycle of chemotherapy was given in July 2014 the general situation of the patient deteriorated and ptosis of the left eye and facial paralysis developed. Then the patient was referred to our medical center. An MR of the brain revealed linear contrast enhancement around the bilateral 3(rd), 7(th) and 8(th) cranial nerves which indicated cranial involvement by the lymphoproliferative process (Figure 1). Cerebrospinal fluid cytological examination confirmed the diagnosis. Based on these and bone marrow aspiration and biopsy findings a diagnosis of T-PLL was rendered (Figure 3). In September 2014 the patient died suddenly due to a cardiac arrest. Differential diagnosis is very important in T-PLL. Both T-PLL and chronic lymphocytic leukemia (CLL) may present with splenomegaly and lymphocytosis as well as circulating prolymphocytes in blood. Typical CLL cells are like mature lymphocytes with dense nucleus and aggregated chromatin. To conclude, CNS involvement in T-PLL is a rare finding and differential diagnosis of T-PLL is very important.

Diffuse Large B Cell Lymphoma with Extensive Cutaneous Relapse.

Herein, we aimed to report a diffuse large B cell lymphoma (DLBCL) case that had extensive cutaneous relapse with no skin involvement previously. A 59-year-old man presented to hospital in April 2014 with fatigue, anorexia, fever, and anemia. Cervical lymph node biopsy revealed CD20+, BCL2+, MUM1+, BCL6+ high grade B lymphoproliferative neoplasm. After FISH investigation, he was diagnosed as DLBCL. He was given 7 cycles of R-CHOP and achieved remission. However, in November 2014, he had emerging skin lesions that cover nearly all of his body. A control PET-CT revealed diffuse cutaneous involvement. CD20+, BCL2+, MUM1+, BCL6+ high grade B cell lymphoma infiltration was detected with skin biopsy. He was diagnosed as relapse lymphoma, so 2 cycles of R-DHAP were given. There was no treatment response; therefore, R-ICE regimen was started. The patient had achieved second complete remission and his skin lesions were completely regressed. The involvement of skin with CD20+ cells after 7 cycles of rituximab therapy favors that there is a rituximab resistant disease which tends to involve the skin. To conclude, DLBCL may relapse extensively with cutaneous involvement and the best treatment option in these patients is salvage chemotherapy followed by autologous peripheral blood stem cell transplantation.

Melanonychia Secondary to Long-Term Treatment with Hydroxycarbamide: An Essential Thrombocytosis Case.

Hydroxycarbamide is used in the treatment of essential thrombocytosis and other myeloproliferative disorders. We report the case of a 63-year-old woman with essential thrombocytosis who had melanonychia after the long-term use of the hydroxycarbamide with a dose of 1000 mg/day. Two years after the initiation of the hydroxycarbamide, our patient had pain on her toes and melanonychia on her nails. Hydroxycarbamide treatment was discontinued because of pain and she was given anagrelide treatment. The pathogenesis of melanonychia secondary to long-term hydroxycarbamide treatment is not yet well understood. Some investigators suggested that genetic factors, induction of melanocytes, and some changes in nail matrix could be the reason of hydroxycarbamide related melanonychia. Our patient has suffered color changes in her nails as well as pain that made us doubtful for a beginning of ulceration besides melanonychia. Maybe early clinical reaction of discontinuation of the drug has prevented more severe side effect like ulceration in our patient. Also side effect of hydroxycarbamide has developed more slowly in our patient compared to other patients in the mentioned study. To conclude, long-term hydroxycarbamide treatment can cause mucocutaneous side effects and more studies should be done in future in order to reveal the underlying mechanism.