Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. METHODS: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. RESULTS: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). CONCLUSIONS: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment.

Study for the diagnostic screening of paroxsymal nocturnal hemoglobinuria in Turkey: Prospective multicentric evaluation of suspected patients.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. METHODS: We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. RESULTS: Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. CONCLUSIONS: Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

The role of hepcidin, GDF15, and mitoferrin-1 in iron metabolism of polycythemia vera and essential thrombocytosis patients

Background/aim: GDF15, hepcidin and mitoferrin-1 (mfrn-1) are proteins involved in systemic iron regulation. There are no studies in the literature demonstrating the serum mfrn-1 levels in polycythemia vera (PV) and essential thrombocythemia (ET) patients. The aim of this study was to investigate GDF15, hepcidin and mfrn-1 levels in PV and ET patients. Materials and methods: Ten PV, 17 ET patients, and 27 healthy controls (HCs) were enrolled. GDF15, hepcidin and mfrn-1 values were measured with enzyme-linked immunosorbent assay (ELISA). Results: GDF15 levels were higher in the myeloproliferative neoplasm (MPN) group (P = 0.002). Hepcidin levels were not different between MPN patients and HCs. The mfrn-1 levels were lower in MPN patients (P = 0.039). Hepcidin, GDF15, and mfrn-1 levels were not different between PV and ET patients. mfrn-1 levels were lower in ET patients than HCs (P = 0.038). Conclusion: Increased erythropoiesis in MPNs may lead to high GDF15 levels in these patients. However, hepcidin was not suppressed despite the increased GDF15 levels and erythropoiesis in these patients. Decrease in mfrn-1 in MPNs can be the result of its increased turnover due to increased myelopoiesis. It can be hypothesized that similar hepcidin levels in patients and controls and low mfrn-1 levels in patients may be a defense mechanism against erythroid activity and thromboembolic complications.

Dasatinib-induced immune mediated-thrombotic thrombocytopenic purpura.

Most commonly seen side effects with Tyrosine kinase inhibitors (TKI's) are hematologic toxicities. Besides, with dasatinib autoimmune side effects can be seen. Thrombotic thrombocytopenic purpura (TTP) is a life- threatening disease that can be related to various causes mainly autoimmune disorders or antineoplastic drugs. Few cases of TKI associated secondary thrombotic microangiopathies (TMA) have been reported in literature. Most of cases were diagnosed as hemolytic uremic syndrome (HUS) rather than TTP. Herein, we describe a 37-year-old CML patient who was diagnosed as immune-mediated TTP related to dasatinib.

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

OBJECTIVE: 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. METHODS: The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. RESULTS: The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. CONCLUSION: The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability.

Beta-2 microglobulin predicts the outcome after autologous stem cell transplantation in non-Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) is an established therapeutic modality in the treatment of lymphomas, especially in the relapse setting. In the present study, we aimed to define pretransplantation factors including Beta-2 microglobulin (ß2m) that influence outcomes following ASCT in patients with non-Hodgkin lymphoma (NHL). We analyzed retrospectively 78 NHL patients who had undergone ASCT from August 2010 to January 2013. The 2-year overall survival (OS) was 70% and the progression-free survival (PFS) was 60%. While remission status less than complete remission (CR) emerged to be a poor prognostic factor for OS in univariate analysis, high ß2m levels and comorbidity indices revealed to be independent poor risk factors for both OS and PFS. The present study demonstrated that even if the patient is in CR before ASCT if he has high ß2m, the 2-year OS decreases from 100% to 49%. Moreover, lymphopenia for the first time was demonstrated to predict PFS in ASCT in NHL patients. Our findings suggest that ß2m at transplantation predict the outcome after ASCT in NHL and further investigation with larger sample sizes is warranted.

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

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 × 10(9)/L were significantly increased compared with ITP patients with thrombocyte counts less than 30 × 10(9)/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.

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, ß-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.

Do Alarmins Have a Role in Multiple Myeloma?

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM.

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

OBJECTIVES: 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). METHODS: The study included 29 patients and 21 healthy controls. The patient group included 13 patients with ET and 16 patients with PV. Serum hepcidin and GDF-15 levels were measured at the time of diagnosis, before the initiation of any therapy. RESULTS: Hepcidin levels did not differ significantly in patients with chronic myeloproliferative disease (CMPD) and healthy controls. However, GDF-15 levels were significantly increased in patients with CMPD (P = 0.038). No difference could be found between patients with PV and ET in terms of hepcidin and GDF-15 levels. Patients with JAK2-V617F mutation had increased GDF-15 levels when compared with patients without this mutation (P: 0.006). CONCLUSIONS: The levels of GDF-15 were higher in CMPD, which are characterized by increased erythropoiesis, and this effect was more pronounced particularly in individuals with JAK2-V617F mutation. Hepcidin levels were not suppressed despite the increased erythroid activity and GDF-15 levels may be protective against the clinical complications of the disease such as thrombosis. This study revealed that, hepcidin levels were not suppressed despite increased erythroid activity and high GDF-15 levels in CMPD. We hypothesized that, this may be an attempt to prevent further amplification of erythropoietic activity by reducing iron utilization.

Effects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.

Correction to: Efects of AGEs, sRAGE and HMGB1 on Clinical Outcomes in Multiple Myeloma.

[This corrects the article DOI: 10.1007/s12288-022-01574-6.].

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.

Prognostic Value of Serum Soluble Klotho and Fibroblast Growth Factor-23 in Multiple Myeloma Patients.

Multiple myeloma is the plasma cell malignancy in which bone involvement is common. The Fibroblast growth factor-23 (FGF-23)/Klotho pathway plays a major role in mineral metabolism that FGF-23 is mineralization inhibitory. Klotho also has anti-apoptotic and anti-tumor effects by acting as a tumor suppressor gene. There is a negative correlation between serum FGF-23 and serum soluble Klotho (sKL) levels. As such, there can be considerable interest in investigating sKL and FGF-23 as a biomarker in patients with MM. We used an enzyme-linked immunosorbent assay to measure serum FGF-23 and sKL levels in 55 newly diagnosed MM patients and 23 healthy controls. We determined significantly high serum FGF-23 and low serum sKL levels in MM patients when compared to healthy controls. Serum sKL levels correlated negatively with a p53 positive mutation status, with high ISS, elevated lactate dehydrogenase, C-reactive protein, Beta-2 microglobulin levels. Serum FGF-23 levels are associated negatively with serum phosphorus and positively only light chains and p53 mutation. Patients with high serum FGF-23 levels had significantly shorter median overall survival than those with low serum FGF-23 levels (p = 0.008). Additionally, low sKL levels were related to decreased overall survival, but they didn't reach statistically significant (p = 0.072). There is a significant correlation between low serum sKL, high FGF-23 levels, and known prognostic factors in MM patients. We conclude that low sKL and high FGF-23 levels are a probable prognostic biomarker for poor MM patient outcomes.

Programmed Cell Death Ligand 1 Expression Level and Prognostic Significance in Acute Myeloid Leukemia.

Purpose: We aimed to evaluate the expression level of programmed death ligand-1 (PD-L1) and its effects on prognosis in acute myeloid leukemia. Methods: The flow cytometry was used to detect PD-L1 expression on leukemic cells of 86 de novo acute myeloid leukemia patients with longitudinal follow-up. Results: Median follow-up was 13 (0-73) months. The mean of expression level was 3.22 ± 0.47 at diagnosis and ranged from 0 to 28%. PD-L1 expression tended to be lower in patients with acute promyelocytic leukemia (2.47 ± 1.08, p = 0.09) but there was no significant difference between neither diagnostic nor cytogenetic subgroups. There was no difference in PD-L1 levels between the patients who achieved complete remission (3.4 ± 0.61) and those who did not (2.91 ± 0.72, p = 0.94). The patients with low PD-L1 at diagnosis (median 25 mo [95% CI; 0-56.7]) had a longer overall survival compared with high PD-L1 (median 13 mo [95% CI; 5.52-25.17], p = 0.079). PD-L1 expression was lower at relapse (2.04 ± 0.79) compared to initial diagnosis (4.52 ± 0.93, p = 0.049). The patients who had overall survival longer than 1 year showed lower PD-L1 expression at relapse (0.66 ± 0.93) compared with who had not (5.06 ± 4.28, p = 0.052). A negative correlation between CD33 and PD-L1 (r = - 0.303, p = 0.005) was detected. Conclusion: Despite its low expression levels, PD-L1 appears to be a clinically important prognostic factor. The negative correlation determined between PD-L1 and CD33 supports the combination approach of PD-L1 inhibitors and CD33 targeted immunotherapies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01473-2.

Are cup-like blasts specific to AML patients with FLT3 ITD and a normal karyotype? An ALL case report and review of the literature.

Cup-like morphology is defined as cup-like nuclear invagination spanning ≥25% of the nuclear diameter in >10% of blasts. Studies have shown that FLT3 ITD and normal cytology are strongly associated with cup-like morphology in acute myeloid leukemia (AML) patients. Herein we describe a patient with cup-like blasts that was diagnosed and treated for common acute lymphoblastic leukemia (ALL). In contrast to the literature, the presented case was Philadelphia chromosome positive and FLT3 ITD negative.

The Role of Interim PET/CT on Survival in Diffuse Large B Cell Lymphoma.

BACKGROUND: Diffuse large B cell lymphoma is the most frequent aggressive non-Hodgkin lymphoma. Predicting response and estimating prognosis earlier makes management of this heterogeneous lymphoma more satisfying. Interim PET response is established in Hodgkin Lymphoma to tailor the therapy but results for non-Hodgkin Lymphoma is unconvincing. In the current study evaluation of interim PET and survival outcomes of 103 DLBCL patients is performed. PATIENTS AND METHODS: About 103 Patients with DLBCL followed up in a single center between 2009 and 2019 were enrolled the study. All patients received R-CHOP chemoimmunotherapy at first line. Interim PET was performed after at least one or more cycles. All PET scans were performed with 18F-FDG isotope as PET/CT. PET scoring results were evaluated according to the 5-Point Deauville Scoring system defined in the National Comprehensive Cancer Network clinical guidelines for iPET and eotPET. 5-P DS of scores of 1 to 3 were defined as negative scans, and scores of 4 to 5 were considered to be positive scans. RESULTS: Forty-six (44.7%) Female and 57 (55.3%) male aged between 25 and 83 (median 57) years newly diagnosed DLBCL patients were enrolled in the study. Median PFS was 21 (interquartile range 8.5-53.7) months and median OS was 33.5 (interquartile range 12.5-62.9) months for the total cohort. Positive predictive value of interim PET according to Deauville scoring system was 65.4% and negative predictive value was 77.9%. CONCLUSION: Our study showed that according to Deauville 5 point scale (D 5PS) scoring system, interim PET-positive patients have shorter both PFS and OS than iPET-negative patients.

Carfilzomib-induced tumor lysis syndrome in relapsed multiple myeloma: a report of two cases.

BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication of cancer therapy characterized by severe electrolyte and metabolic abnormalities such as hyperphosphatemia, hyperkalemia, and hypocalcaemia. TLS usually occurs in aggressive hematologic malignancies such as Burkitt lymphoma and acute leukemia. TLS has rarely been observed in multiple myeloma (MM). CASE REPORT: We present 2 patients with relapsed MM who developed TLS after the first cycle of carfilzomib treatment. CONCLUSION: Carfilzomib is a next-generation proteasome inhibitor with proven efficacy in relapsed/refractory MM. Recently, increasing frequency of TLS has been reported in MM, especially after treatment with proteasome inhibitors. The potential complications of TLS should be considered especially during the first cycle of carfilzomib treatment.

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.

Lymphomas of Waldeyer's ring: Clinical features, management and prognosis of eleven adult patients.

Lymphoma is the second most common neoplasm of the head and neck after squamous carcinoma. The majority of lym¬phomas involving the head and neck are non-hodgkin's lymphomas. Hodgkin's lymphoma is rare in Waldeyer's ring. Between 1999 and 2006, the medical records and pathology data of all newly diagnosed, previously untreated adult patients with Waldeyer's ring lymphomas were retrospectively reviewed. Pathologic specimens were adopted according to WHO his¬tologic classification. All patients were clinically staged with history and physical examination, routine hematologic and bio¬chemical profiles, chest X-ray, and computerized tomography of the head and neck, chest, abdomen and pelvis. All patients were treated with chemotherapy. Approximately one month after the end of the scheduled initial management, patients were restaged for evidence of residual disease with physical examination, laboratory profiles and relevant radiologic studies. Total patient number was 11 in our institution. Complete remission was achieved in 6 patients and partial remission in 3 patients; 1 patient did not achieve remission and 1 patient with anaplastic large cell lymphoma died. Patients who are alive are still being followed in our institution. The progression of patients with lymphoma is closely associated with the diagnosis, stage and histologic grade of the disease. This series characterized the clinicopathologic features and outcomes of adult patients. Our data have shown that there is relatively good survival in these diseases but more patients must be evaluated for mean¬ingful results.