Splenectomy in Immune Thrombocytopenia: A Retrospective Analysis of 25-Year Follow-up Data from a Tertiary Health Clinic.

Immune thrombocytopenia (ITP) is a rare autoimmune disorder presenting with isolated thrombocytopenia. Splenectomy is still one of the treatment alternatives for these patients. Here we aim to analyze long term follow-up data of splenectomy in immune thrombocytopenia. This retrospectively designed study was conducted in a tertiary health clinic. Patients with ITP who were splenectomized between 1990 and 2015 were included. Response to treatment was interpreted as 'complete response', 'response' or 'no response'. The incidence of response loss was evaluated. Perioperative and long term complications and overall survival rates were determined. Out of 51 patients, who underwent splenectomy after 12 months of diagnosis, 47 achieved a response (92.2%). Of 47 patients who had a platelet count at least 30.000/µL, 41 (87.2%) had CR. Incidence of loss of response was 10.5% (95% confidence interval (CI): 4%-26.1%) at 30 months. Two patients died, and overall survival rate was 97.4% (95% CI: 82.8%-99.6%) at 30 months of follow up. Considering the complications: two patients had venous thromboembolism, 11 had minor bleeding episodes and 15 suffered from perioperative infections. Our study suggests that splenectomy promises a high level of response with acceptable complication rates. Although less preferred recently, splenectomy should still be taken into consideration when remission is not achieved especially after 12 months of disease.

Quality of Life and Symptom Burden With First- and Second-generation Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myeloid Leukemia.

BACKGROUND: With the advent of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) have a life expectancy similar to those of age- and gender-matched healthy populations. Nevertheless, patients receiving TKIs report chronic adverse events such as fatigue, edema, and muscle cramps, which lead to a decrease in their quality of life (QoL). Therefore, the aim of this study was to assess the QoL and symptom burden in patients receiving original imatinib, generic imatinib, dasatinib, and nilotinib. PATIENTS AND METHODS: A total of 121 patients with CML who received TKIs for at least 3 months were enrolled in the study. The QoL was assessed with the Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Chronic Myeloid Leukemia (QLQ-CML24) modules. The symptom burden was assessed with MD Anderson Symptom Inventory for Chronic Myeloid Leukemia (MDASI-CML) and EORTC QLQ-CML24. RESULTS: The median age of the study population was 53 years (range, 28-90 years), and 83 (81.4%) patients had a low-to-medium Sokal risk score. The Eastern Cooperative Oncology Group performance status of most patients were good (< 2; 96%), and comorbidity scores were low (HCT-CI < 3; 90.8%). There was no significant difference between the general health status of patients in terms of EORTC QLQ-C30 and QLQ-CML24. According to the results of the MDASI-CML and QLQ-CML24 modules, the most common symptom was fatigue (58.7%) in all groups, and there were no significant differences between the groups in terms of the effects on the daily life activities of the patients. CONCLUSION: Patients with CML receiving first- and second-generation TKIs were seen to have a similar QoL and symptom burden.

Rectal colonization with multidrug-resistant gram-negative bacteria in patients with hematological malignancies: a prospective study.

OBJECTIVES: To investigate the risk factors for rectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) in hematological malignant patients with febrile neutropenia (FN); rate of rectal colonization and infection/colonization with CRE and ESBL-E; whether empirical treatment can be revised. METHODS: Adult patients receiving chemotherapy were included. Rectal swab cultures of patients were screened for CRE and ESBL-E using selective chromogenic agars. RESULTS: Fifty-seven FN episodes of 57 patients were studied. Rectal colonization rates were 40.4% (23/57) and 8.8% (5/57) for ESBL-E and CRE, respectively. ESBL-E bacteremia was diagnosed in 2 (8.6%) ESBL-E colonized patients, while CRE bacteremia was detected in 1 (20%) CRE colonized patient. Amikacin (100%) and carbapenem (93%) were the most effective antibiotics against gram-negative enteric bacteria. Beta-lactam usage within the last 3 months was a significant risk factor for ESBL-E colonization. CONCLUSIONS: For the treatment of FN patients either colonized with ESBL-E or having significant risk factors for ESBL-E infection, aminoglycoside containing combinations may become an alternative to carbapenems due to their high sensitivity rates. When CRE colonized hematological cancer patients develop FN or if they are hemodynamically unstable, CRE covering empiric antibiotherapy should be preferred due to high mortality rates of CRE bacteremia.

Effects of Deeper Molecular Responses on Outcomes in Chronic Myeloid Leukemia Patients in Chronic Phase Treated With Imatinib Mesylate.

BACKGROUND: The prognostic significance of complete cytogenetic response (CCyR) is well defined in patients with chronic phase chronic myeloid leukemia treated with imatinib as first-line therapy. However, the effect on outcomes of obtaining molecular response itself and the depth of it is not clear. In this study we aimed to determine the frequency of complete molecular response (CMR) during long-term follow-up and the clinical significance of CMR on patient outcomes and survival. PATIENTS AND METHODS: We retrospectively evaluated the files of 178 chronic phase chronic myeloid leukemia patients using imatinib therapy. Forty-seven patients with missing data were excluded from the study and the assessment was done in 131 patients. CMR was defined as undetectable BCR-ABL transcripts using real-time quantitative polymerase chain reaction with a sensitivity level of ≥ 104 in 2 consecutive analyses at least 3 months apart. Cytogenetic and molecular monitoring during treatment was performed according to the European LeukemiaNet recommendations criteria. Our primary objective was to analyze the association of deeper molecular response with differences in progression-free survival (PFS). RESULTS: Eighty-eight patients (67%) achieved CMR at any time in a median of 65 months of follow-up. The rate of CMR was higher in patients who achieved CCyR at 12 months and major molecular response (MMR) at 18 months. Fewer events occurred in the CMR group than the MMR group (26.1% vs. 50.0%). Overall survival was not different in both groups. CMR was associated with longer PFS with borderline significance. CONCLUSION: Prolonged imatinib therapy helps to achieve a deeper molecular response in the long-term. Achieving deeper molecular response at any time positively affects maintaining the cytogenetic and molecular responses, and decreases the transformation to accelerated and/or blastic phase. The slight prolongation in PFS did not reach statistical significance.

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 old 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.

Efficacy and safety of eltrombopag in treatment-refractory primary immune thrombocytopenia: a retrospective study.

Eltrombopag was used in patients with chronic primary immune thrombocytopenia (ITP) who did not tolerate or were refractory to two or more previous treatments. The primary aims of the study were to determine the efficacy and safety of long-term eltrombopag treatment. Data were extracted from medical chart records retrospectively. Platelet count of at least 50 000/µl at any time point during the treatment was defined as the 'response'. Median duration of eltrombopag treatment was 29 weeks (11-74). The number of patients who had a platelet count of at least 50 000/µl at any time point was 26 (83.9%). The response was achieved by the second week in most of the patients. Concomitant ITP medications were withdrawn in nine out of the 11 patients. Eltrombopag was discontinued in one patient due to sustained response despite discontinuation of the treatment. Age, sex, concomitant ITP treatments, and previous ITP treatment failures had no impact on the treatment response. The treatment was discontinued due to thrombosis in only four patients. Four patients experienced a minor bleeding event. Hepatotoxicity and all other adverse events were mild and manageable. Eltrombopag is effective, safe, and well tolerated in the long-term treatment of chronic ITP patients.

Miliary Tuberculosis Induced Acute Liver Failure.

Hepatobiliary tuberculosis is uncommon even in endemic countries. It is associated with a high mortality and is even diagnosed early in the disease course. Acute liver failure (ALF) caused by tuberculosis bacilli has been reported in only a few reports. All previous cases have been diagnosed by postmortem examination. Time to antituberculosis treatment is very critical. In case of suggestive findings on clinical and radiologic examination, antituberculosis treatment should be initiated immediately. Drug use can be a challenge in patients with ALF. However, as long as the other possible causes of ALF can be excluded and hepatotoxic drugs were avoided during the early course of treatment, such a highly fatal presentation of tuberculosis can be treated safely. Here, we report a case of acute liver failure as a presentation of miliary tuberculosis. He was treated successfully with antituberculosis treatment.

Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide? A retrospective analysis of data from the GIMEMA, Nordic and Turkish myeloma study groups.

BACKGROUND/AIM: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. PATIENTS: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. RESULTS: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. CONCLUSION: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study.

Relationship of P-selectin glycoprotein ligand-1 to prognosis in patients with multiple myeloma.

BACKGROUND: Changes occur in adhesion molecules in the disease course of multiple myeloma. P-selectin glycoprotein ligand-1 (PSGL-1, CD162) works as the ligand of selectin-neutrophil adhesion molecules. The aim of the present study was to investigate the relationship between PSGL-1 expression in the bone marrow and the known prognostic factors for multiple myeloma disease, disease stage, and survival. MATERIALS AND METHODS: This research included 63 patients with multiple myeloma (26 women [41.3%]; 37 men [58.7%]). The bone marrow biopsy samples obtained at disease diagnosis for each patient were stained immunohistochemically in terms of CD162 expression using standard diagnostic immunohistochemical staining methods. The laboratory results, CD162 expression, overall survival, demographic characteristics of the disease, and the relationship between CD162 expression and the disease stage were evaluated. RESULTS: Among the 63 patients included in the present study, the survival rate was 82.3% for 1 year, 73.2% for 2 years, 63.4% for 3 years, 51.7% for 4 years, 40.3% for 5 years, and 33.6% for 6 and 7 years. A statistically significant difference was not detected between the CD162 staining ratio and disease survival (P = .232). A statistically significant difference was not detected between the CD162 staining degree and survival rate (P = .184). However, the overall survival of the patients with no CD162 expression in the bone marrow was lower than that for the patients whose CD162 was stained 1, 2, and 3 degrees (12.33 ± 11.49, 28.65 ± 31.44, 37.25 ± 29.32, and 47.92 ± 45.29 months, respectively; P < .001). CONCLUSION: In the present study, CD162 staining and the staining degree, with the other standard immunohistochemical stains, were shown to be beneficial in the diagnosis of multiple myeloma disease. However, the results did not provide information about the disease course. Studies of a larger number of patients to examine P-selectin and interleukin-6 levels are needed to investigate the disease course.

Aplastic anemia associated with oral terbinafine: a case report and review of the literature.

Onychomycosis (OM) is a common fungal infection of the toenails and/or fingernails that is highly prevalent in the general population and also responsible for significant morbidity. OM is caused by dermatophytes, nondermatophytic molds, or yeast. Today systemic antifungal agents are considered as the gold standard for all types of OM. Here we report a case of aplastic anemia associated with oral terbinafine use and a review of the literature on hematological toxicities associated with terbinafine.

Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases.

BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC.

Newly diagnosed breast cancer in a patient receiving imatinib mesylate.

Imatinib mesylate is the standard treatment of chronic myeloid leukemia (CML). Despite imatinib is being used in the treatment of other malignancies as well, its potential role on de novo tumor growth is not known. Secondary malignancies are rarely seen in patients with CML and particularly in those receiving imatinib. Here, we present a CML patient taking imatinib therapy that was diagnosed to have breast cancer and received adjuvant chemo-and radiotherapy with imatinib. We tried to explain co-occurrence of these rare events by probable pathogenetic mechanisms.

Bortezomib in patients with renal impairment.

Renal failure is a common manifestation of multiple myeloma (MM). Bortezomib is primarily metabolized by cytochrome p450 isoforms. It also has a cytochrome-independent metabolism by excretion through the bile and kidney. Based on our observations, we aimed to explore the efficacy and toxicity profiles of bortezomib in 56 patients with MM, 24 of which had moderate to severe renal failure. Overall response and complete response, as well as very good partial response rates, were comparable between patients with normal renal functions and renal impairment. The median overall survivals for patients with estimated glomerular filtration rates of <60 and ≥60 ml/minute were similar. Although there was a tendency for shorter overall survival along lower estimated glomerular filtration rates, this difference did not reach a statistical significance. Overall and severe adverse events, and dose modification and treatment discontinuation rates were higher in patients with renal impairment. Patients with renal failure had more thrombocytopenia and diarrhea. While thrombocytopenia was mild to moderate and manageable, diarrhea, which led to serious adverse events, was more severe in patients with renal failure who received bortezomib as monotherapy. Bortezomib appears to be active; however, when used alone, it may cause more frequent and severe adverse events in patients with MM and renal failure.

Addition of thalidomide to oral melphalan/prednisone in patients with multiple myeloma not eligible for transplantation: results of a randomized trial from the Turkish Myeloma Study Group.

The combination of melphalan-prednisone-thalidomide (MPT) has been investigated in several clinical studies that differed significantly with regard to patient characteristics and treatment schedules. This prospective trial differs from previous melphalan-prednisone (MP) vs. MPT trials by treatment dosing, duration, routine anticoagulation, and permission for a crossover. Newly diagnosed patients with multiple myeloma (MM) (n=122) aged greater than 55 yr, not eligible for transplantation were randomized to receive 8 cycles of M (9 mg/m(2) /d) and P (60 mg/m(2) /d) for 4d every 6 wk (n=62) or MP and thalidomide (100 mg/d) continuously (n=60). Primary endpoint was treatment response and toxicities following 4 and 8 cycles of therapy. Secondary endpoints were disease-free (DFS) and overall survival (OS). Overall, MPT-treated patients were younger (median 69 yr vs. 72 yr; P=0.016) and had a higher incidence of renal impairment (RI, 19% vs. 7%, respectively; P=0.057). After 4 cycles of treatment (n=115), there were more partial responses or better in the MPT arm than in the MP arm (57.9% vs. 37.5%; P=0.030). However, DFS and OS were not significantly different between the arms after a median of 23 months follow-up (median OS 26.0 vs. 28.0 months, P=0.655; DFS 21.0 vs. 14.0 months, P=0.342, respectively). Crossover to MPT was required in 11 patients, 57% of whom responded to treatment. A higher rate of grade 3-4 infections was observed in the MPT arm compared with the MP arm (22.4% vs. 7.0%; P=0.033). However, none of these infections were associated with febrile neutropenia. Death within the first 3 months was observed more frequently in the MP arm (n=8, 14.0%) than in the MPT arm (n=2, 3.4%; P=0.053). Long-term discontinuation and dose reduction rates were also analyzed (MPT: 15.5% vs. MP: 5.3%; P=0.072). Although patients treated with MPT were relatively younger and had more frequent RI, better responses and less early mortality were observed in all age groups despite more frequent discontinuation.

Low levels of protein Z are associated with HELLP syndrome and its severity.

Protein Z (PZ) was found to be associated with pregnancy complications. There are no data implying an association between hemolysis (H), elevated liver enzymes (EL), and low platelet counts (LP) (HELLP) syndrome and changes in plasma levels of PZ. The aim of this study is to investigate whether HELLP syndrome is associated with plasma concentrations of PZ. Protein Z levels in 29 women with HELLP syndrome were compared with 29 healthy, nulliparous and 25 normal pregnant women. The median PZ levels in patients with HELLP syndrome were found to be significantly lower than those of pregnant women. No significant difference was found between HELLP and healthy groups. Protein Z levels correlated with platelet counts, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels in patients with HELLP syndrome. Median PZ level was higher in partial HELLP than in complete HELLP. We calculated 1330 ng/mL as a cutoff value for PZ level to discriminate HELLP syndrome from normal pregnancy. Low PZ levels are associated with the pathobiology of HELLP syndrome.

Precursor B cell lymphoblastic lymphoma presenting as a solitary bone tumor: a case report and review of the literature.

Precursor B cell lymphoblastic lymphoma (B-LBL) is quite uncommon and it usually manifests as an extranodal disease. Although B-LBL may present with bone involvement, it is a very rare manifestation of B-LBL as a primary solitary bone tumor. Here, we report a case of precursor B-LBL presenting with solitary bone tumor and a review of a total of seven adult patients reported previously in the literature. We described demographic and clinical characteristics of these patients with unique presentation and discussed treatment options. Unlike previous reports except one case, our patient underwent allogeneic stem cell transplantation (allo-SCT) due to refractory disease. She is alive without evidence of disease by the post-transplant 12th month. B-LBL has an aggressive clinical course in adult patients and allo-SCT may be the best treatment option.

A case of Cauda Equina syndrome in a leukemic patient due to intrathecal methotrexate.

The leukemias may cause neurologic dysfunction through either direct invasion of the nervous system or indirectly through cytopenias, or it may occur as a result of the necessarily vigorous treatment programs for leukemia. We report here a 24-year-old acute lymphoblastic leukemia patient who in her second cycle of hyper-CVAD chem therapy regimen (high-dose Ara-C and high-dose methotrexate) received intrathecal methotrexate and two days afterwards was diagnosed as having Cauda Equina syndrome (CES). A lumbo-sacral MRI imaging with gadolinium was performed and there was a remarkable enhancement in the Cauda Equina region, suggesting either leukemic involvement or a type of neurologic complication associated with intrathecal methotrexate treatment. To rule out leukemic involvement, a lumbar puncture was performed and the CSF was free of leukemic cells. There are cases of CES developing after spinal anesthesia reported in the literature, but this is the first report of CES due to intrathecal methotrexate.

Complete heart block in a neutropenic patient with invasive aspergillosis.

A patient with leukemia who developed complete heart block after the diagnosis of pulmonary aspergillosis is reported. The patient had probable invasive pulmonary aspergillosis with a sudden tachypnea, dyspnea, fever, bilateral pulmonary infiltrates and acute respiratory insufficiency after chemotherapy. On the sixth day of antifungal therapy, she developed complete atrioventricular block. Complete heart block has not been reported during liposomal amphotericin B (LAMB) therapy. Local or hematogenous involvement of the myocardium with aspergillosis may be the most likely explanation of the complete heart block.

Myelodysplastic syndrome with pseudoreticulocytosis.

A patient with myelodysplastic syndrome (MDS) with refractory anemia who had marked reticulocytosis in the absence of hemolytic anemia and/or blood loss is reported. Erythrocyte survival test showed that more than 50% of the patient's reticulocytes were still present on day seven. This should be due to the prolongation of reticulocyte maturation in MDS, and is known as pseudoreticulocytosis. This phenomenon which mimicks hemolytic anemia is an unusual presentation of myelodysplastic syndrome, with only 7 patients with pseudoreticulocytosis being reported previously.