Pinar Tarkun

Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib

We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.

Serum hepcidin and growth differentiation factor-15 (GDF-15) levels in polycythemia vera and essential thrombocythemia

Hepcidin plays a regulatory role in systemic iron homeostasis. GDF‐15 has been found to be expressed from matured erythroblasts and very high levels of GDF‐15 suppresses hepcidin secretion. In this study, we evaluated hepcidin and GDF‐15 levels in polycythemia vera (PV) and essential thrombocythemia (ET).

Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP) Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.

Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients.

Background/Aims: Multiple myeloma (MM) is a hematological cancer associated with increased clonal malignant plasma cells. Growth differentiation factor 15 (GDF 15) is a protein that is highly expressed in the bone marrow mesenchymal stem cells of patients with MM. This study investigated whether the clinical stage of the disease, treatment response and survival are affected by pretreatment serum GDF 15 levels. Methods: Serum GDF 15 levels were measured in 35 newly diagnosed MM patients and 27 healthy controls. The correlation between serum GDF 15 levels and various clinical and laboratory parameters was analyzed. Results: The study demonstrated significantly higher levels of GDF 15 in MM patients. There was a negative correlation between GDF 15 levels, hemoglobin and albumin levels, and a positive correlation between GDF 15 levels, CRP, creatinine, β-2-microglobulin and stage. GDF 15 levels were lower in patients who could receive autologous stem cell transplantation compared to other groups, representing a statistically significant difference. However, in the survival analyses, GDF 15 level did not have an impact on survival. Conclusion: High serum levels of GDF 15 may indicate a poor treatment response. Our study supports the prognostic value of GDF 15 in MM.

Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

Two‐thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high‐dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment‐related toxicities in patients treated with conventional and novel protocols.

The Association Between Gene Polymorphisms and Leukocytosis with Thrombotic Complications in Patients with Essential Thrombocythemia and Polycythemia Vera

Objective: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. Material and Methods: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. Results: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn’t an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren’t any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn’t a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L–1) than in those without leukocytosis (leukocyte count ≤10 × 109 L–1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). Conclusion: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years o ld who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Decreased serum heat shock protein 60 levels in newly diagnosed immune thrombocytopenia patients.

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by peripheral thrombocyte destruction. In some autoimmune disorders, heat-shock proteins (HSP) are suggested to be an important antigenic factor. In this study, we demonstrated the serum free levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 in ITP patients and healthy controls. Twenty-eight newly diagnosed ITP patients, 35 ITP patients in chronic phase, and 25 healthy controls were enrolled to this study. Serum levels of HSP60, HSP70, anti-HSP60, and anti-HSP70 were determined by the ELISA method. Serum HSP60 levels of newly diagnosed ITP patients were significantly decreased when compared with both chronic phase ITP patients and healthy controls. HSP60 levels of ITP patients (both newly diagnosed and chronic phase) with thrombocyte counts more than 30 × 109/L were significantly increased compared with ITP patients with thrombocyte counts less than 30 × 109/L and there was a positive correlation between thrombocyte counts and serum free HSP60 levels in ITP patients. This is the first study demonstrating the extracellular HSP levels in adult ITP patients. HSPs are shown to have a place in the pathogenesis of many autoimmune disorders. Low level of HSP60 may lead to lack of anti-inflammatory response due to less Treg activation, hence, could be a counterpart in the pathogenesis of ITP. Further studies are needed to understand the role of HSPs in the pathogenesis of ITP and whether they can be used for diagnosis, prognosis, and treatment of ITP.

Late-onset Anticonvulsant Hypersensitivity Syndrome Mimicking Lymphoma.

Anticonvulsant hypersensitivity syndrome is a fatal, idiosyncratic drug reaction that is caused by aromatic antiepileptic drugs. This cutaneous drug reaction is also called pseudolymphoma because of its clinical and histological similarities with malignant lymphoma. The primary clinical findings are fever, skin rashes, enlarged lymph nodes, single or multiple internal organ involvement and hematological abnormalities. Typically, anticonvulsant hypersensitivity syndrome occurs 1-8 weeks after drug administration. We herein present the case of a patient who had been on anticonvulsant therapy for five years and died from late-onset anticonvulsant hypersensitivity syndrome.

A Rare but Fatal Complication Probably due to Imatinib: Cerebral Edema

Imatinib mesylate is a tyrosine kinase inhibitor that strongly inhibits the tyrosine kinases like BCR-ABL1, KIT and PDGFRB and is used in the treatment of chronic myeloid leukemia. As well as its proven effectiveness its frequent side effects are also well known. Apart from its other side effects its commonly encountered side effect in daily clinical use is edema. Although the path-physiology of this process has not yet been well understood, its strong blocking action on PDGFRB is thought to be responsible. In this case report we are presenting a chronic myeloid leukemia patient with cerebral edema who unfortunately died. To our knowledge, she has been the third patient who was reported due to this complication of imatinib. As we could not estimate another cause we strongly deduced that the cerebral edema was due to imatinib.