Lupus-like symptoms with anti-RNP/Sm and anti-nuclear antibodies positivity: An extremely rare adverse event of dasatinib.

INTRODUCTION: Dasatinib is a potent tyrosine-kinase inhibitor which is used for chronic myeloid leukemia treatment. Pleural effusion is a frequent side effect in patients during dasatinib treatment. Pulmonary arterial hypertension is a rare and life-threatening adverse event of dasatinib. The relationship between dasatinib and autoimmune disorders is unclear, but there are reports of possible mechanisms that have triggered autoimmunity by dasatinib. CASE REPORT: A 53-year-old male was diagnosed with chronic myeloid leukemia and initiated imatinib mesylate as a treatment. Imatinib was changed to dasatinib as the patient was unresponsive in the first year of treatment. In the fourth year of dasatinib when chronic myeloid leukemia was in both hematological and cytogenetical remission, the patient presented with bilateral massive exudative pleural effusion. Echocardiography was consistent with pericardial effusion with right ventricle enlargement and normal left-side cardiac function. Pulmonary arterial hypertension was diagnosed with high systolic pulmonary arterial pressure. When he had fever and arthralgia, further investigation showed positivity of anti-nuclear antibodies (1/160 titer) and anti-RNP/Sm, which have high specificity for the diagnosis of Systemic Lupus Erythematosus (SLE). MANAGEMENT AND OUTCOME: Dasatinib was discontinued and nilotinib was initiated. As the pleural effusion persisted despite diuretics and methylprednisolone, mycophenolate mofetil was initiated as a steroid-sparing immune-suppressive agent. The lupus-like symptoms disappeared, and antibodies became undetectable after dasatinib discontinuation. Pericardial effusion improved and pleural effusion did not relapse. DISCUSSION: Screening for auto-antibodies may be recommended for patients with a history or symptoms of autoimmune disease before starting dasatinib. All patients who develop pleural effusion while on dasatinib treatment should be investigated for antibodies for lupus.

Vitamin D Deficiency and Janus kinase 2 V617F Mutation Status in Essential Thrombocythemia and Polycythemia Vera.

INTRODUCTION: Vitamin D, which is known for its effects on calcium and bone metabolism, has recently been associated with haematological malignancies. We aimed to investigate the relationship between disease findings and vitamin D deficiency in essential thrombocythemia (ET) and polycythemia vera (PV). MATERIAL AND METHODS: This retrospective cohort study conducted in Turkey included 73 patients diagnosed with PV or ET according to WHO criteria between 2012 and 2018. Vitamin D deficiency was defined as 25-OH vitamin D < 20 ng/mL. Polymerase chain reaction (PCR) was used to detect the Janus kinase 2 (JAK2) V617F mutation. RESULTS: Vitamin D deficiency was found in 66.7% of PV and 74.2% of ET patients. The median follow-up time of ET and PV patients was 48 months and 47 months, respectively. Patients with the JAK2 mutation had a higher prevalence of a history of thrombosis and age older than 65 years. There was a significant relationship between JAK2 positivity and vitamin D deficiency. CONCLUSION: There was a remarkably higher prevalence of vitamin D deficiency in JAK2 mutation-positive ET and PV patients. These patients should be carefully evaluated for vitamin D deficiency. More studies are required to further investigate the association between JAK2 and vitamin D.

Acute pancreatitis caused by bortezomib.

Drug-induced pancreatitis has been reported rarely. Bortezomib is a selective and reversible proteasome inhibitor used for the treatment of patients with multiple myeloma (MM). Recently, one case report about acute pancreatitis (AP) caused by bortezomib was published in the international literature. Herein we report a case of AP in a 67-year-old male on bortezomib therapy. On the fourth day after the first administration of bortezomib, the patient admitted to the hospital with symptoms of AP. The common etiological factors for AP were all excluded. Than the patient was diagnosed as bortezomib-induced pancreatitis.

A case of thrombotic thrombocytopenic purpura associated with bupropion.

OBJECTIVE: To report a case of bupropion-associated thrombotic thrombocytopenic purpura (TTP) syndrome. CASE SUMMARY: A 55-year-old man was admitted with complaints of diarrhea, acute renal failure, and confusion ~ 54 days after bupropion initiation for smoking cessation. Subsequently he had a tonic-clonic seizure and had to be intubated because of altered consciousness. Laboratory findings were compatible with microangiopathic hemolytic anemia. He was diagnosed as TTP for which the Naranjo adverse drug reaction probability scale indicated a probable relationship with bupropion (a score of 5). He was treated with plasma exchange, systemic corticosteroids, hemodialysis and recovered fully. DISCUSSION: Bupropion is an anti-depressant drug also indicated for smoking cessation. It has widely reported neuropsychiatric and allergic adverse effects; however, TTP associated with bupropion has only been reported once. The clinical course of TTP in this case was compatible with TTP related to acute, immune mediated drug toxicity, which suggests that auto-antibodies might have been responsible. CONCLUSIONS: Given the fact that the clinical condition is compatible with acute, immune-mediated TTP syndrome, we suggest bupropion deserves evaluation for auto-antibody induction. Prescribers should be aware of the possible risk of thrombocytopenia and TTP.

A Giant Mass in the Eyelid: Peripheral T-Cell Lymphoma, Not Otherwise Specified.

Purpose: To report a case with an unusual giant mass in the eyelid which was diagnosed as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Methods: A 40-year-old woman was referred with a 1-year history of rapidly and constantly growing eyelid mass. Results: The patient underwent an incisional biopsy and histopathological examination revealed a PTCL-NOS. After achieving regression by the combination of cyclophosphamide, hydroxydoxorubicin, vincristine (oncovin), etoposide, and prednisolone therapy, the remaining crusts were debrided, the eyelids were separated, and the wound was left to heal by secondary intention. Cicatricial ectropion of the lower eyelid occurred during follow-up and it was corrected with a free skin graft successfully. Conclusion: PTCL-NOS is uncommon but it may reach massive dimensions in the eyelid region.

Prognostic Value of the Expression of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR-1) in Chronic Lymphocytic Leukemia.

Background: The transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1) has acted on the causation and sustentation of mature B-cell lymphomagenesis for chronic lymphocytic leukemia (CLL) cells. The study attempted to show whether there is a relationship between the level of ROR1 surface expression in CLL cells and disease findings. Materials and Methods: The level of ROR1 cell surface expression was determined in accordance with the flow cytometric analysis of CLL patients at the first diagnosis time.  Two groups were formed according to the high and low ROR1 levels. The cut-off point for the ROR1 level was calculated for advanced-stage disease using receiver operating characteristic (ROC) curves. A two-sided p-value <0,05 was considered statistically significant. Results: 108 CLL cases with a median age of 60 were enrolled. The median percentage of ROR1 cell surface marker positivity in the CD5/CD19 positive leukemic cell was 62%. The CLL cases with high ROR1 levels have thrombocytopenia (p=0.042), anemia (p=0.028), and high beta-2 microglobulin value ≥3 mg/dL (p=0.002) and the need for first-line treatment (p=0.043). Conclusion: The poor prognostic parameters such as splenomegaly, anemia, higher beta-2 microglobulin levels, intermediate/advanced RAI stage disease, and need for first-line treatment had associated high-level ROR 1 expression of our CLL patients. It needs to be investigated for its effect on predicting disease burden and aggressiveness with more comprehensive studies on ROR1 expression levels in CLL cases.

The effects of plasma viscosity in thromboembolic events among patients with essential thrombocytosis: A case-control study.

INTRODUCTION: Essential thrombocythemia (ET) is an entity of classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by thrombocytosis with megakaryocytic hyperplasia where in the thrombocytes are increased with abnormal function.Thrombotic events are seen frequently and represent the main cause of morbidity and mortality in patients with MPNs, mainly polycythemia vera and ET. This study has aimed to research the effects of clonally increased thrombocytes on plasma viscosity (PV) levels among patients with ET and the relationship between PV and thromboembolism history, according to the hypotheses about the effects of PV in thromboembolic events among patients with ET. METHODS: A total of 55 patients were enrolled in the study group, 18 of who had been newly diagnosed with ET according to 2016 World Health Organization criteria and had not previously been treated. 37 of them had already been diagnosed with ET and had been treated. There were 47 healthy volunteers in the control group. 5 cc blood samples were taken from the patients into tubes including an anticoagulant to measure their PV levels. RESULTS: PV of the control group was found to be lower than in the study group and both each patient groups (p < 0.05). No relationship was found between the patient groups in terms of PV (p = 0.404). The mean PV levels of the 16 patients with a history of thromboembolism and the 39 patients with no such history were 2.42±0.17 cP and 2.33±0.20 cP, respectively. The mean PV levels were found to be similar according to their history of thromboembolism in all patient groups and in treated patients (p = 0.572 vs p = 0.991). CONCLUSION: We have found that PV levels were increased in clonally increased thrombocytes in patients with ET when compared with the control group. This is the first study in this field according to our knowledge.

Predictive Factors for Molecular Response in Chronic Myeloid Leukemia: Reduction Ratio and Halving Time of BCR::ABL1 IS Transcript Levels

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

Mean platelet volume is a predictive and prognostic marker for patients with acute myeloid leukemia: a two-center retrospective analysis.

There are only a few predictive markers that can truly aid therapy decisions in patients with acute myeloid leukemia (AML). The current study aimed to examine the impact of easily available common laboratory parameters on the course and prognosis of patients with AML. Gender, initial bone marrow blast percentage, mean platelet volume (MPV), lymphocyte-to-monocyte ratio, treatment regimen, and complete remission (CR1) were found to have a statistically significant effect on both OS and PFS (p < 0.05). Only MPV, LDH, and initial treatment regimen were found to have a significant effect on CR1 achievement (p < 0.05). According to the current study, besides the induction regimen, only MPV was seen to affect short and long-term outcomes including both CR achievement, OS and PFS. MPV can be considered as a predictive or prognostic marker in patients with AML. Patients with higher MPV at the time of diagnosis should be evaluated carefully.

VAD Chemotherapy versus Bortezomib Containing Regimens as Remission Induction For ASCT in Multiple Myeloma: A Single Center Experience.

Background: Complete response (CR) and very good partial response (VGPR) are targeted with pre-ASCT induction regimens in patients by diagnosed multiple myeloma (MM), who are candidates for ASCT. In this study, it was aimed to compare the response and survival evaluations of cases who underwent induction treatment by vincristine-doxorubicin-dexamethasone (VAD) protocol versus bortezomib containing regimens. Materials and Methods: The data of 96 ASCT eligible patients, retrospectively analyzed. P value> 0.05 was considered statistically significant. Results: While 66 cases had received bortezomib containing regimens as induction regimen, 30 cases had received VAD protocol. The total survival was 91.3 (st.s 6) months and 43 (st.s 7.9) months, respectively, when we compared the cases without ASCT and with ASCT (p = 0.001). The OS of patients who underwent ASCT after reaching at least VGPR was longer than the underwent ASCT without reaching VGPR (p=0.019). Post-ASCT PFS (p=0.717) and OS (p = 0.126) analyzes were performed in 74 cases undergoing ASCT treatment, there was no significant statistical difference when patients with treated by VAD protochol and treated by bortezomib containing regimens as pre-ASCT induction regimens was compared to each other. Conclusion: Whatever the type of induction regimen is, the level of response achieved before ASCT is important. The survival of the myeloma patients are much more influenced with HDT-ASCT as well as post-transplantation strategies to keep the patients in remission. Even though it is outdated, we think that the VAD protocol may be an option in patients who are not responding with the new generation of agents in the following days.

The Triple Positivity for EBV, PD-1, and PD-L1 Identifies a Very High Risk Classical Hodgkin Lymphoma.

BACKGROUND: The programmed death receptor (PD-1) and ligand (PD-L1) pathway act by suppressing the antitumor response in chronic Hodgkin lymphoma (cHL). In this study, we aimed to investigate the effect of PD-1, PD-L1, and Epstein-Barr virus (EBV) positivity on prognosis at the initial diagnosis of cHL. MATERIAL AND METHODS: Thirty-six patients with cHL were retrospectively analyzed. PD-L1 staining was performed for RS cells and tumor microenvironment in the biopsy materials of cases. The presence of EBV was investigated by EBER (EBV-encoded RNA) method in tumor cell. P < .05 was accepted as significant. RESULTS: The presence of advanced-stage disease, B symptoms, intermediate or high-risk international prognostic index (IPS), and extranodal involvement were found to be related to both PD-L1 positivity and EBV positivity in RS cells. PD-L1 positivity in RS cells was also associated with EBV positivity. There were 6 (16.7%) triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) patients. All of these patients had advanced-stage disease, B symptoms at the time of diagnosis, and intermediate-high IPS score, and 4 of 6 patients had extranodal involvement. This group also had significantly shortened overall survival compared with others (38.4 months vs. 67.9 months P = .024). CONCLUSION: Our data suggest that there is correlation between PD-L1 positivity and EBV positivity in tumor RS cells that are also associated with extranodal involvement, intermediate and high IPS score, presence of B symptoms, and advanced-stage disease. In addition, we identified a group of triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) cHL patients who have a very high-risk disease.

Is Cd11c and Fmc7 Negativity in Chronic Lymphocytic Leukemia Poor Prognostic?

Chronic lymphocytic leukemia (CLL) is a common hematological malignancy. This study is aimed to investigate the prognostic effect of clinic, laboratory and flow cytometric analysis in CLL patients. Newly diagnosed 55 CLL cases were divided into two groups, as stable disease (Group 1) and progressive disease (Group 2). Group 1 included those who did not require any treatment since diagnosis and those who did not progress after receiving the first step anti CLL treatment. Group 2 included the patients who received ≥ 2 steps treatment. The relation between the two groups was analyzed statistically in terms of clinical, laboratory and flow cytometric findings. Twenty patients (36.3%) required treatment at the time of diagnosis, four patients (3.8%) received first-line treatment during follow-up and 31 (56.3%) patients were followed without any treatment. Thirteen patients required second step treatment after a median of 26.3 months. The risk of progression was found to be increased 5-fold (p = 0.015) in the CD38 positive patient group, 4.2-fold (p = 0.0147) in the FMC7 negative patient group and 2.8-fold in the CD11c negative patient group. FMC 7 negativity decreased total survival 5.9-fold (p = 0.051). Unlike similar publications, we found that patients with CD11c or FMC7 negativity were in a higher need for ≥ 2 step treatment. This suggests that CD11c or FMC7 negativity may be used as a poor prognostic marker in CLL.

Prognostic Value of Baseline Serum Lactate Dehydrogenase Level in Patients With Hairy Cell Leukemia.

BACKGROUND: Hairy cell leukemia is a rare B-cell lymphoproliferative disorder. It has an indolent course with relapse and remission periods. The aim of this study was to investigate the clinical characteristics and risk factors affecting the outcome of patients with hairy cell leukemia. PATIENTS AND METHODS: The retrospective data of 65 patients were evaluated according to initial hematologic and biochemical parameters, response rates, progression-free survival, and overall survival. Factors effecting response and survival rates were analyzed. RESULTS: The median follow-up duration was 62.8 months (range, 5.7-229.3 months). The result of the analysis showed that the patients with relapse/progressive disease had higher lactate dehydrogenase (LDH) levels at the time of diagnosis than patients without relapse/progression (median [range], 243 [137-540] vs. 179 [99-334] U/L, P = .01). Patients with LDH ≥ 200.5 IU at the time of diagnosis were demonstrated to have a shorter progression-free survival than those with LDH < 200.5 IU (P = .010). CONCLUSION: Serum LDH level is significantly associated with relapse/progression in hairy cell leukemia patients. Patients with higher LDH levels at diagnosis should be monitored closely even if they experience complete remission.

Thiol-disulphide Homeostasis in Essential Thrombocythemia Patients.

BACKGROUND: This study aimed to show the status of thioldisulphide homeostasis in essential thrombocytosis patients, which is known to play a role in platelet function. METHODS: The study included 27 ET patients and a control group of 36 healthy subjects. Serum total (-SH + -S-S-) and native (-SH) thiol levels were measured in all subjects using an automatic method. RESULTS: Age and gender distribution were similar in both groups. Compared with the control group, in the ET group, there were increased native thiol and total thiol levels (p = 0.001, p = 0.046). There was no correlation between thiol, total thiol and disulphide ratios with Jak2 mutation, hemorrhage and thrombosis. A positive correlation was determined between thrombosis and thiol disulphide homeostasis (p = 0.058). The study results showed that thiol-disulphide homeostasis shifted to the proliferative side in ET, in which ineffective erythropoiesis was predominant. It is also known that platelets are more active in ET cases and thiol disulphide balance is important in platelet function. CONCLUSIONS: This result suggests that thrombotic complications may be reduced if the formation is achieved of mechanisms (oxidation mechanisms) that will trigger the increase of disulphide groups. However, more extensive research is needed on this subject.

Acute myeloblastic leukemia-associated Marfan syndrome and Davidoff-Dyke-Masson syndrome: a case report.

We present herein a 23-year-old man with acute myeloblastic leukemia (AML) associated with Davidoff-Dyke-Masson syndrome (DDMS) and Marfan syndrome (MS). The diagnosis of DDMS was based on findings including left facial asymmetry, left hemiparesis, mental retardation, right cerebral hemiatrophy, dilatation of the ipsilateral lateral ventricle and calvarial thickening. The diagnosis of MS was based on clinical findings including tall stature, myopia, retinitis pigmentosa, blue scleras, scoliosis, pectus excavatum, arachnodactyly and low ratio of upper/lower body segment. The patient developed hepatosplenomegaly, gingival hypertrophy and pancytopenia. Peripheral blood film and bone marrow examination showed that most of nucleated cells were blasts; immunophenotype of those cells showed CD11+, CD13+, CD14+, CD33+ and HLA-DR+. These findings confirmed the diagnosis of AML (FAB-M5). After induction chemotherapy, remission was obtained. To the best of our knowledge, our case is the third report of AML in MS syndrome, while AML associated with DDMS and MS has not been previously reported in the literature.

Acquired hemophilia with thrombosis in a cancer patient: an unusual presentation.

: Acquired hemophilia A (AHA) which presents with spontaneous severe intramuscular, mucosal and/or subcutaneous bleeding is a rare bleeding disorder. Even 50% of AHA patients are defined as idiopathic; 10% of cases are related with malignancy. Here, we present a case of AHA in a 43-year-old lady who was diagnosed with malignancy and venous thromboembolism on vena cava 2 years ago. To the best of our knowledge, this is the first report in literature presented with both acquired hemophilia and thrombosis associated with malignancy. A routine workup for malignancy like solid tumors, lymphoproliferative, or myeloproliferative diseases should be performed and followed up for a long time despite clinical improvement for individuals presented with AHA. Moreover, because of warfarin treatment, the diagnosis may be difficult and delayed. Clinicans should rule out AHA in patients who are on warfarin treatment and have abnormal coagulation tests.

Development of plasma cell leukemia in a patient with chronic myeloid leukemia while on treatment with imatinib mesylate.

Plasma cell leukemia (PCL) is a rare and an aggressive form of plasma cell dyscrasias. We report a 67-year-old male with PCL which developed while on imatinib mesylate (IM) therapy 38 months after diagnosis of chronic myeloid leukemia (CML). The patient has been treated successfully with bortezomib, melphalan and prednisolone. To our knowledge, only one case of PCL superimposed on Philadelphia positive CML has been reported in the literature and this was before the IM era.

[Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections]. / Streptokok enfeksiyonu ile iliskili OKB ve tik bozuklugu olan dört olguda plazmaferez tedavisine yanit.

The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections.