Hakan Harputluoglu

Rituximab-related viral infections in lymphoma patients.

Recently, a human/mouse chimeric monoclonal antibody, rituximab, has been successfully used to treat cases of B-cell non-Hodgkins lymphoma and some autoimmune diseases. However, several viral infections related to rituximab have been reported in the literature, but were not well characterized. To further investigate this topic, relevant English language studies were identified through Medline. There were 64 previously reported cases of serious viral infection after rituximab treatment. The median age of the cases was 61 years (range: 21 – 79). The median time period from the start of rituximab treatment to viral infection diagnosis was 5.0 months (range: 1 – 20). The most frequently experienced viral infections were hepatitis B virus (HBV) (39.1%, n = 25), cytomegalovirus infection (CMV) (23.4%, n = 15), varicella-zoster virus (VZV) (9.4%, n = 6), and others (28.1%, n = 18). Of the patients with HBV infections, 13 (52.0%) died due to hepatic failure. Among the 39 cases that had viral infections other than HBV, 13 died due to these specific infections. In this study, about 50% of the rituximab-related HBV infections resulted in death, whereas this was the case in only 33% of the cases with other infections. Close monitoring for viral infection, particularly HBV and CMV, in patients treated with rituximab should be recommended.

Infectious complications of rituximab in patients with lymphoma during maintenance therapy: a systematic review and meta-analysis.

Rituximab maintenance therapy has emerged as an effective treatment for low-grade lymphomas. No major acute or cumulative toxicities were observed in patients receiving rituximab maintenance therapy compared with observation arms in clinical trials. However, B-cells are completely depleted throughout the maintenance period and even longer, which may render patients at high risk for infections. Several infections related to rituximab have been reported in the literature. Yet it is not clear whether rituximab maintenance therapy increases the infectious complications or not. To further investigate this topic, we have performed a systematic review and meta-analysis of randomised controlled trials (RCT). The meta-analysis of five RCTs showed that rituximab maintenance therapy significantly increased the relative risk of both infection and neutropenia in patients with lymphoma. On the basis of the available evidence, patients who received rituximab maintenance treatment have higher risk of neutropenia and infection than those who did not. Previously treated patients particularly with fludarabine containing regimens are more susceptible to infectious complications and require extended vigilance.

Sonographic and Electrodiagnostic Evaluations in Patients With Aromatase Inhibitor-Related Arthralgia

PURPOSE To investigate the prevalence of arthralgia in breast cancer patients taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment including autoimmune serology, musculoskeletal sonography, and electromyography (EMG) in these patients. PATIENTS AND METHODS Postmenopausal patients with stage I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92). Patients who were not receiving hormone treatment were included as a control group (n = 28). Musculoskeletal sonography and EMG were applied to the patients and the controls along with markers of autoimmunity. RESULTS Thirty patients (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most commonly affected joints were knee (70%), wrist (70%), and small joints of the hand (63%). Patients taking AIs had increased tendon thicknesses compared with those who never received AIs (P < .001). Patients with AI-related arthralgia had higher rates of effusion in hand joints/tendons than those without arthralgia (P = .033). More patients with AI-related arthralgia had EMG findings consistent with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No significant difference was observed in erythrocyte sedimentation rates, C-reactive protein, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, or anticyclic citrullinated peptide levels between patients and controls or between those with and without arthralgia. CONCLUSION Patients with AI-related arthralgia often show tenosynovial changes suggesting tenosynovitis, exerting local problems but lacking a systemic inflammatory component. Our finding of increased CTS frequency also supports this hypothesis.

Breast cancer subtypes and outcomes of central nervous system metastases

Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2-0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287-0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically‐verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 ± 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut‐off point of <7.4 fl was found to have significant predictive value according to receiver‐operating characteristics curve analysis. This cut‐off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20–135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

Characteristics of Breast Cancer Patients with Central Nervous System Metastases: A Single-Center Experience

The aim of this study was to assess the characteristics of breast cancer patients with central nervous system (CNS) metastases and factors associated with survival after development of CNS metastasis. One-hundred-forty-four patients with brain metastases were retrospectively analyzed. Median age at the time of brain metastasis diagnosis was 48.9. Median time between initial diagnosis and development of brain metastasis was 36 months. Fourteen cases had leptomeningeal involvement. Twenty-two patients (15.3%) had single metastasis. Ten percent of the patients had surgery, 94% had radiotherapy and 63% had chemotherapy. Median survival after development of brain metastasis was 7.4 months. Survival of patients with single metastasis was significantly longer than those with multiple metastases (33.5 vs. 6.5 months, p = 0.0006). Survival of patients who received chemotherapy was significantly longer than those who received radiotherapy alone (9.9 vs. 2 months, p < 0.0001). In multivariate Cox regression analyses, presence of single metastasis and application of chemotherapy were the only significant factors associated with better survival (p = 0.047 and p < 0.0001, respectively). Age at initial diagnosis or at the time of brain metastasis, time from initial diagnosis to development of brain metastasis, menopausal status, tumor stage, grade, hormone receptor or HER2 status individually were not associated with survival. In this study, survival after the diagnosis of CNS metastases appeared to be affected by patient characteristics rather than biologic characteristics of the tumor. This is probably secondary to the lack of effective treatment options in these patients and overall poor prognosis.

Metastatic granular cell tumor: A case report and review of the literature

To the EditorGranular cell tumors (GCT) are uncommon benigntumors. They may occur in various sites. The tongueand breast comprise the two most common loca-tions, while a lesion in the digestive and respiratorytracts is not unusual. Laryngeal involvement is fairlyuncommon and is present in approximately 10% ofall cases [1]. Malignant GCTs represent less than2% of all granular cell tumors [2]. As with theirbenign counterparts, malignant GCT have a wideanatomic distribution. However, they carry a poorprognosis, with recurrence and metastasis typicallywithin one year of diagnosis [3].We present a case of malignant granular celltumor arising from larynx, which has metastasizedto lungs and bones. We also conducted a search onthe MEDLINE database (National Library ofMedicine, Bethesda, MD) and identified 52 pre-viously reported cases of metastatic GCT whosesurvival data were reported. Basic characteristics ofthese cases together with ours are described in thefollowing sections. We also review the metastaticGCT in literature.Case ReportA 43-year-old woman was admitted to the hospitalfor long-standing cough and recent hemoptysis. Inher past history, she had undergone right verticallaryngectomy in another institution two years ago.The diagnosis was laryngeal GCT. Physicalexamination was unremarkable except for decreasedbreath sounds in the apex of the right lung. Chestx-ray revealed infiltration of right upper lung region.Computed tomography (CT) of the thorax showedmediastinal lymphadenopathies as well as a lesionthat partially obstructed the upper lobe bronchusand invaded the inferior vena cava. Bronchoscopyrevealed a bright, smooth and vascularized mass,obstructing the right upper lobe entrance. Punchbiopsy was performed. Histopathological examina-tion showed a GCT. The lesion appeared inoperabledue to the invasion of large vessels. Ultrasound andCT of the abdomen showed a giant hemangioma inthe right lobe of the liver. This finding was con-firmed by biopsy. Sixty Gy of external radiotherapywas administered to the pulmonary lesion.This intervention resulted in the palliation of he-moptysis, but the size of the lesion remained stable.As no other effective treatment modality wasavailable, a decision to administer chemotherapywas made. She received three cycles of cisplatinand fluorouracil. Toxicity was acceptable, however,the pulmonary lesion remained unchanged whilemultiple osteoblastic lesions appeared on directx-rays and radionuclide bone scan. Chemotherapywas discontinued, and she was given radiotherapy tothe right distal femur for pain palliation. Oraletoposide 50 mg/day was prescribed, but patientcould not tolerate and refused to use it after onlyten days of treatment.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well‐documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV(+) patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High‐risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co‐infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience

Background: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). Patients and Methods: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m2 on days 1–14 of a 21-day cycle). Results: The median follow-up was 10.5 months (range 1–38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5–9), with a median overall survival of 13 months (95% Cl 9–17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3–4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. Conclusion: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.

Lower bone mineral density in geriatric patients with monoclonal gammopathy of undetermined significance

The aim of this study was to investigate the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a geriatric population in Turkey and compare bone mineral densities and related laboratory parameters of MGUS patients with those who do not have MGUS. Among 1,012 patients enrolled, monoclonal band was detected in serum samples of 22 patients (2.17%), most of which were IgG type. Further tests revealed multiple myeloma and lung carcinoma in two patients. The remaining 20 patients were diagnosed with MGUS (1.97%). The clinical and laboratory parameters of patients with and without MGUS were mostly comparable; however, bone mineral density measurements of patients with MGUS were significantly lower than those without MGUS (p = 0.007). We suggest evaluation of geriatric patients with MGUS for the presence of osteopenia/osteoporosis considering the high frequency observed in this study.