Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Combination therapy with azacitidine, etoposide, and cytarabine in the treatment of elderly acute myeloid leukemia patients: A single center experience.

AIMS: The prognosis of acute myeloid leukemia (AML) in elderly patients is worse due to age and comorbidities. Lately, monotherapy with hypomethylating agents like azacitidine (Aza) has been used to prolong overall survival (OS) in AML patients. Herein, we present a retrospective study investigating treatment responses and OS of Aza in combination with etoposide (Eto) and cytarabine (ARA-C) in elderly. MATERIALS AND METHODS: In this study, therapies and outcomes of 37 newly diagnosed AML patients, >60 years old, and ineligible for intensive chemotherapy were investigated retrospectively. Patients were grouped according to the treatments they received as follows - Group 1: low-dose conventional therapies as hydroxyurea, low-dose ARA-C, or best supportive care (n = 11); Group 2: Aza alone (n = 6); Group 3: Aza in combination with Eto and ARA-C (Aza + Eto + ARA-C, n = 20). RESULTS: It was found that an Aza + Eto + ARA-C combination therapy had significantly better overall response rates (P = 0.002). Combination group had significantly better OS than Group 1 (8 months vs. 1 month, P < 0.001), the difference between combination and monotherapy was not significant. The OS was also associated with age and performance status, but the difference was still statistically significant after adjustment for these factors, especially for patients with younger age and better performance. CONCLUSIONS: We concluded that combination therapy of Aza with Eto and ARA-C increases response rates, and prolong survival for this poor prognosed patient group. We believe that larger controlled studies investigating Aza combinations with other antileukemic drugs will contribute to the development of tolerable treatment protocols for elderly AML patients.

The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple Myeloma: A Single Center Experience.

BACKGROUND: Recent studies have shown a positive correlation between tumor-related immune response markers and the poor outcome in solid tumors. In this study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple myeloma. To the best of our knowledge, this would be the second report concerning this topic. METHODS: We retrospectively reviewed the data for 52 multiple myeloma patients. The patients were grouped using the baseline NLR as NLR ≤ 1.72 and NLR > 1.72 using receiver operating characteristic analysis to determine a cut off. We compared the two groups in terms of both the known prognostic factors of the myeloma and the overall survival (OS). RESULTS: Our study showed that NLR is associated with C-reactive protein and ß2 microglobulin (P = 0.02 and P = 0.001, respectively). The patients with NLR > 1.72 had significantly worse stages, performance status, and kidney functions. The whole group's OS was estimated as 35.1 months while the patients with lower NLR had better OS when compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P: 0.04). CONCLUSION: Neutrophil/lymphocyte ratio, which is associated with stage, performance status, and kidney functions, can be used in daily practice as a predictor for survival in multiple myeloma. Simply adding NLR to the routine charts may enrich our data for larger studies.

Comparative Evaluation of Common Comorbidity Scores and Freiburger Comorbidity Index as Prognostic Variables in a Real Life Multiple Myeloma Population.

Multiple myeloma (MM) is a disease of the geriatric population with a median age at diagnosis of 69 years but most clinicians consider performance status and comorbidities rather than chronological age in determining prognosis and treatment. The purpose of this study was to assess whether and which comorbidity indices predict survival in a real life population of MM. We calculated Charlson Comorbidity Index (CCI), age combined Charlson index (CCI-age), Hematopoietic cell transplantation-specific comorbidity index (HCT-SCI) and Freiburger comorbidity index (FCI) retrospectively for 66 MM patients and compared their impact on treatment responses and overall survival (OS). Treatment response was significantly worse in groups with high CCI, CCI-age, HCT-SCI scales (p < 0.05), but FCI's effect on treatment response was not significant. However, while no significant relationship was determined between other comorbidity indices with OS, it was related only with FCI-CI (p = 0.006). FCI, developed in this patient group, was the only prognostic index with a significant effect on OS in the evaluation of comorbidities in MM patients with different scores, but its relationship to treatment responses was not significant contrary to other indices. While this small patient group gave us hope regarding the use of FCI in practice, multi-center studies are still required.

The effect of duration of nasal obstruction on mean platelet volume in patients with marked nasal septal deviation.

Nasal obstruction is a common cause of marked nasal septal deviation. It is related strongly with hypoxia. Hypoxic conditions increase mean platelet volume levels. This study aimed to investigate the effect of age on mean platelet volume in patients with marked nasal septal deviation. We made a retrospective study of patients with marked nasal septal deviation between January 2012 and May 2014. The patients were divided into four groups according to duration of nasal obstruction (less than 10, 10-20, 20-30 and more than 30 years). The groups were compared with each other in terms of mean platelet volume, platelet distribution width, platelet count in preoperative hemogram. This study was performed on 356 male and 139 female patients. Mean age was 33.9 ± 12.3 years. It was determined that the platelet count, mean platelet volume did not constitute statistically significant difference between groups (p > 0.05). Nevertheless, it was determined that as the duration of nasal obstruction elongated the mean platelet volume value increased and platelet count values decreased. Mean values of platelet distribution width constituted statistically significant difference between all groups (p = 0.026). Patients with marked nasal septum deviation should be subjected to surgery as soon as possible because of the increase in mean platelet volume and platelet distribution width values which are related to increase in the risk of cardiopulmonary complications of nasal obstruction.

Serious skin reaction associated with imatinib in a patient with chronic myeloid leukemia.

Imatinib mesylate (STI 571) is one of the fundamental chemotherapeutic agents used in the treatment of the chronic, accelerated and blastic phases of chronic myelocytic leukemia (CML), gastrointestinal stromal tumors and Philadelphia chromosome-positive acute lymphoblastic leukemia. It selectively inhibits receptor tyrosine kinases. Its effects limit the use of this drug. We present a case with a serious skin reaction requiring the discontinuation of the drug and that developed in relation to imatinib therapy. Six months prior, a 61-year-old male patient presenting to the hematology polyclinic with complaints of weight loss and sweating was hospitalized due to high leukocyte value. As a result of the hemogram, biochemistry analyses, peripheral blood smear examination, bone marrow aspiration evaluation, cytogenetic examination using FISH and PCR that were performed, CML was diagnosed. Additionally, to exclude myelofibrosis, we examined a bone marrow biopsy. Imatinib mesylate was started at 400 mg/day orally. In the fourth month of treatment, the patient complained of itching and a skin rash. Although the drug dose was reduced (300 mg/day), his complaints gradually increased. The skin biopsy result was superficial perivascular dermatitis. Imatinib was discontinued, and the patient was started on corticosteroid. The lesions disappeared completely. A month later, the patient was restarted on imatinib mesylate. However, the lesions recurred more prominently. His itching increased. The patient was considered intolerant to imatinib mesylate, and a second-generation tyrosine kinase inhibitor, dasatinib 100 mg/day, was started orally. The follow-up and treatment continues for the patient, who has been taking dasatinib 100 mg/day for the last two months without any skin finding or complaints. Imatinib mesylate-induced skin reactions are associated with the pharmacologic effect of the drug rather than hypersensitivity to the drug. Skin reactions are frequently observed, and this side effect is dose dependent. However, the interesting aspect of our case was that despite dose reduction, skin findings gradually increased, and eventually the drug had to be discontinued.

Cerebrovascular accident during cisplatin-based combination chemotherapy of testicular germ cell tumor: an unusual case report.

Even though testicular nonseminomatous germ cell tumors (NSGCTs) usually have a good prognosis and high curability rates, unpredicted complications owing to chemotherapy regimens might complicate the course. Modalities that are commonly used to cure NSGCTs have well-known side effects. Thromboembolism, which is infrequently associated with germ cell tumors and the vascular toxicity of chemotherapeutics, causes morbidity and mortality. We report a young testicular NSGCT patient, without any known underlying risk factor, who experienced an unpredicted cerebrovascular accident after he received cisplatin-based combination chemotherapy.

Mycophenolate mofetil treatment of crescentic Henoch-Schönlein nephritis with IgA depositions.

Mycophenolate mofetil (MMF) is considered to be a promising therapeutic agent in primary glomerulonephritis but there are no data on the use of MMF in Henoch-Schönlein nephritis (HSN). Herein we report the first adult crescentic HSN patient in whom long-term complete remission was achieved after MMF therapy.

Cavernous sinus syndrome caused by metastatic colon carcinoma.

Cranial metastasis has been reported as infrequent during colon cancers and usually occurs in the late stages with liver and/or lung metastasis. Metastasis to cavernous sinus is even rarer and only reported as case reports in the literature. In patients with cavernous sinus metastasis, the most common primary sites are the breast, lung, and genitourinary carcinomas, if head and neck tumors are excluded. A 34-year-old man underwent a right hemicolectomy for a mucinous adenocarcinoma of the right colon 14 months before presentation. Because metastatic implants on the omentum were detected during the operation, combination chemotherapy was begun. After 5 months of the last cycle of the chemotherapy, his left eyelid began to droop, left eye movements became limited, and he began experiencing numbness of his right forehead and cheek. Clinical and radiologic findings were discussed. Despite antiedematous treatment and radiation therapy, he did not experience marked improvement of his symptoms. He could not be given chemotherapy and died 2.5 months after the first symptom of cavernous sinus metastasis. Primary colon adenocarcinoma with cavernous sinus metastasis is very rare. It was hypothesized that the paravertebral plexus of Batson could permit the spread of tumor cells from pelvis toward the cranium. This could explain the metastases from pelvis to the cavernous sinus, such as in our case. Prognosis for the patients with cavernous sinus metastasis seems to be poor, and this might be the harbinger of rapid progression with widespread disease.