The prognostic value of serum levels of a proliferation-inducing ligand (APRIL) in treatment-naïve patients with chronic lymphocytic leukemia

Background/aim: A proliferation-inducing ligand (APRIL) has been investigated as a prognostic marker in chronic lymphocytic leukemia (CLL) patients. However, there is no cut-off level for serum APRIL (sAPRIL) levels that predict time to treatment in CLL patients. Materials and methods: Between May and December 2012, 94 consecutive CLL patients and 25 healthy controls were assessed. sAPRIL levels were measured by ELISA. Demographic data and prognostic markers were obtained from the patients' files. Treatment-naïve patients were followed up for 6.5 years for any treatment need. Results: Patients were divided into 3 groups: Treatment-naïve (n = 47), chemotherapy receiving (n = 25), and those who had received chemotherapy previously (n = 22). There was no difference in median sAPRIL levels of patients who were receiving chemotherapy at the sampling time and the healthy controls, which indicates that sAPRIL levels might be influenced by treatment. For treatment-naïve patients, the best cut-off in predicting time to treatment was found at the sAPRIL level of 2.04 ng/mL, with 78% sensitivity and 63% specificity. Time to treatment was significantly earlier in the APRIL high group (n = 27) than in the APRIL low group (n = 20) (P = 0.010, log-rank test). Conclusion: sAPRIL, a simple, promising blood test which can be measured by ELISA, will likely obtain a place in the wide range of prognostic markers in CLL. Prospective large-scale studies are required to validate and confirm the feasibility of the proposed cut-off level of 2.04 ng/mL as a predictor of time to treatment in treatment-naïve CLL patients.

Hepatitis B reactivation in hematopoietic stem cell transplanted patients: 20 years of experience of a single center from a middle endemic country.

Hematopoietic stem cell transplantation (HSCT) is a risk factor for viral hepatitis reactivations because it affects lymphocyte number and functions. Latent hepatitis B virus (HBV) may stay in dormant form in hepatocytes and may be reactivated in prolonged immunosuppression. This study analyzes the incidence of reactivation of HBV infections in HSCT patients in a middle endemic country like Turkey. Five hundred and sixty-one HSCT patients from 1994 to 2015 were retrospectively evaluated. Sixty-six patients had a serologic feature of HBV infection. Fifteen patients were hepatitis B surface antigen (HBsAg)-positive patients (3 allogeneic and 12 autologous) while 51 of them were anti-hepatitis B core IgG (anti-HBc IgG)-positive patients (22 allogeneic and 29 autologous). Although under lamivudine prophylaxis, reactivation was seen in three of 12 (25%) chronic HBV (HBsAg positive) patients who received autologous HSCT and in two of the three HBsAg-positive patients who received allogeneic HSCT. Rate of reactivation in the whole HBsAg-positive group was 33%. Reactivation occurred on median 270th day (range: 60-730). Reverse seroconversion incidence was 10% on 133th day for HBsAg negative, but anti-HBc IgG-positive patients, which increased to 17% on 360th and to 23% on 1500th day. Cumulative incidence increased to 41% on 2280th day for isolated anti-HBc IgG-positive patients. Hepatitis B surface antibodies (anti-HBs) were found to be protective as reactivation did not exceed 11% on 5050th day when anti-HBs was positive. When anti-HBc IgG-positive cases were analyzed according to their transplantation types, allogeneic HSCT was found to have higher cumulative incidence (45% on 3258th day) for HBV reactivation than autologous HSCT (7% on 5050th day). Besides, HBV reactivation in anti-HBc IgG-positive patients who received allogeneic transplantation was related to mortality. Findings of this study suggest that HBV prophylaxis extending over 1 year should be prescribed for HBsAg-positive patients independent of the transplantation type. Prophylaxis should also be given to anti-HBc IgG-positive patients if an allogeneic HSCT is to be performed.

Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

Age-Related Co-Expression of BCOR and BCORL1 mRNA in Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematological malignancy caused by a variety of genetic abnormalities and epigenetic dysregulation. The incidence of AML is strongly related to age, with the highest incidence rates being in older adults. The loss of function mutations in BCOR and BCORL1 genes have been identified in AML. BCL6 corepressor (BCOR) and BCL6 corepressor like 1 (BCORL1) are important epigenetic regu-lators as a member of Polycomb repressive complex 1 (PRC1.1), involved in histone modification processes. METHODS: We analyzed the BCOR and BCORL1 mRNA expression in 74 adult and 22 pediatric patients with AML by Real-Time quantitative PCR in this study. RESULTS: Our results indicated that both BCOR and BCORL1 mRNA expressions decrease with age (p = 0.009 and p = 0.008, respectively) and there is a positive correlation between BCOR and BCORL1 mRNA expression (p < 0.001). BCOR and BCORL1 mRNA expressions were not significantly different in both adult and pediatric patients with AML compared to control (p > 0.05). CONCLUSIONS: Our findings indicate that expression of BCOR and BCORL1 mRNA are down-regulated with age. The increase in AML incidence with age suggests that age-associated BCOR and BCORL1 down-regulation might potentially contribute to age-related epigenetic alterations and form a predisposing condition for the development of elderly AML.

Hematopoietic cell transplantation activity of Turkey in 2014: Ongoing increase in HCT rates.

Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity.

Generic imatinib in the treatment of chronic myeloid leukemia: Cerrahpasa experience.

As the first tyrosine kinase inhibitor (TKI), imatinib (Gleevec or Glivec, Novartis Pharmaceuticals) was introduced, the treatment of chronic myeloid leukemia (CML) has changed radically, and the TKIs are now the mainstay of CML treatment. The substantially high treatment cost has unfortunately been a major issue, which puts a strain on health-care budgets even in developed countries. So reimbursement policies encourage generic drug (i.e. generic imatinib) use to lower the expenses, and it is true that generics would lead to considerable cost savings, but they also give rise to questions associated with their efficacy, safety and quality. In this commentary, we discuss the current evidence on generic imatinib based mainly on our "Cerrahpasa" experience along with other data available in the literature together with the data discussed by de Lemos and colleagues.

A reappraisal of the association between Behçet's disease, myelodysplastic syndrome and the presence of trisomy 8: a systematic literature review.

OBJECTIVES: A number of patients with Behçet's disease (BD) associated with myelodysplastic syndrome (MDS) with or without trisomy 8 have been reported. A high frequency of gastrointestinal (GI) involvement was reported in such patients. The aim of this systematic literature review was to delineate whether GI involvement is an inherent feature of BD associated with MDS, whether these patients do actually have BD rather than GI symptoms related to MDS, and whether the presence of trisomy 8 plays a role in the disease expression of BD associated with MDS. METHODS: A systematic literature review was performed in PubMed using the keywords (Behçet's disease OR Behçet's syndrome) AND (myelodysplastic syndrome OR trisomy 8) until December 2013. RESULTS: Data from 39 manuscripts that met the inclusion criteria, reporting on 52 patients were analysed. GI involvement was common in reports from both the Far East and non-Far East countries (75% vs. 50.0%, p=0.15). These patients had typical BD manifestations, except for 1 patient who had only oral ulcers and gastrointestinal involvement. The presence of trisomy 8 seems to be associated with an increased frequency of fever (79.5% vs. 33.3%, p=0.005). CONCLUSIONS: GI involvement seems to be an inherent feature of BD associated with MDS regardless of geographic differences. Despite the increased frequency of GI involvement in these patients, MDS does not seem to modify the clinical expression of gastrointestinal involvement. Presence of trisomy 8 seems to modify the disease expression with an increased frequency of fever.

Postoperative thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of thrombocytopenia and microangiopathic hemolytic anemia occurring due to platelet and von Willebrand factor deposition and hyaline thrombi formation in arterioles and capillaries throughout the body, which results in organ ischemia. TTP can be idiopathic or secondary, and there are several causes of secondary TTP. There is a clinical syndrome resembling TTP that occurs after surgical procedures, so-called "postoperative TTP" (pTTP). In this review, the differential diagnosis, pathogenesis and clinical and laboratory features of pTTP, together with the treatment modalities and outcomes of the patients, are discussed. The pTTP is a diagnosis of exclusion, and disseminated intravascular coagulation, heparin-induced thrombocytopenia and medication-induced effects should be ruled out. As in classical TTP, patients with pTTP should be diagnosed and treated with therapeutic plasma exchange (TPE) as early as possible to reduce their morbidity and mortality. Although rarely seen, surgeons and physicians of all specialties should be alert to the possibility of pTTP, and since pTTP is a life-threatening event that usually can be treated successfully with TPE, especially when diagnosed early in its course, it is critical to recognize and treat pTTP promptly.

Bone marrow transplantation for Behçet's disease: a case report and systematic review of the literature.

OBJECTIVES: Behçet's disease (BD) can be life threatening and may be refractory to corticosteroids and immunosuppressives. There has been some experience with haematopoietic stem cell transplantation (HSCT) in BD either for severe, refractory disease or for a haematological condition. The objectives of this study were to describe a BD patient undergoing HSCT and to evaluate the outcomes of BD patients who underwent HSCT. METHODS: We report a BD patient with refractory gastrointestinal (GI) involvement who had HSCT for concomitant myelodysplastic syndrome (MDS). We also performed a systematic literature search regarding HSCT for either refractory disease or concomitant haematological conditions in BD patients. RESULTS: A 30-year-old woman with refractory GI BD involvement with trisomy 8 MDS underwent a successful myeloablative allogeneic HSCT resulting in complete resolution of both BD and MDS. Additionally we identified 14 manuscripts providing data on 19 patients with BD who had HSCT. Among these 20 patients, including ours, refractory disease was the indication of transplantation in 9, while 11 patients were transplanted because of accompanying haematological conditions. Transplant indications for the nine patients (four male, five female) with refractory BD were neurological involvement in five, pulmonary artery aneurysm in two, GI disease in one and not reported in one patient. Three patients with neurological disease, both patients with pulmonary artery aneurysm and the patient with intestinal involvement achieved complete remission of their disease. Six patients transplanted for haematological conditions, including the presented case, also had GI involvement of BD. All of these patients achieved complete remission of GI findings after HSCT. CONCLUSION: When considering HSCT, the potential adverse events and complications, which can be fatal, need to be kept in mind.

Bone-Specific Alkaline Phosphatase Levels among Patients with Multiple Myeloma Receiving Various Therapy Options.

OBJECTIVE: This study aimed to investigate the impact of the different therapy regimens used in multiple myeloma (MM) on bone-specific alkaline phosphatase (BALP) levels. MATERIALS AND METHODS: One hundred and thirteen patients with MM were included in the study. Patients were grouped according to the regimens they received, as follows: group 1, melphalan and prednisolone (MP); group 2, vincristine, adriablastin, and dexamethasone (VAD); group 3, thalidomide plus dexamethasone; and group 4, bortezomib plus dexamethasone. BALP levels were measured before treatment and at the third and sixth months of treatment. A fifth group consisted of patients in the post-treatment remission period at study entry (no-treatment group). RESULTS: The BALP levels at the third and sixth months of the treatment were significantly higher than the pre-treatment levels in the bortezomib and the no-treatment groups, whereas no significant difference was observed in the MP, VAD, and thalidomide groups. CONCLUSION: Considering that BALP is a surrogate marker of bone formation, our study suggests that bortezomib more efficiently leads to the improvement of bone disease in myeloma than other treatment options.

Complications of therapeutic plasma exchange: A retrospective, single-center study of 2505 procedures performed in 338 patients over 15 years.

INTRODUCTION: Therapeutic plasma exchange (TPE) may involve complications. We aimed to review the demographic data, indications, technical information, and complications. METHODS: Data for TPE procedures (TPEPs) performed between 2004 and 2018 were retrospectively. RESULTS: This study covered 2505 TPEPs performed on 338 patients; 55% of them were female (n = 186), and the median age was 36 years (range, 11-93 years). Most TPEPs were administered for hematological (40.6%) indications. The incidence of complications on the first procedure was 3.2% (n = 80); only 16 procedures (0.6%) were failed. The complication incidence was 19.8% (n = 497), with 789 total complications. Most of the complications were patient-related (90.4%), and the most of them were urticaria (29.1%), occlusion (3.2%), and faulty systems (1.01%), respectively. The use of only fresh frozen plasma as replacement fluid caused a higher complication rate (22.1%, p < 0.01). CONCLUSION: The number of TPEPs is increasing every day. Hematologic indications for TPE and the use of fresh frozen plasma may increase the risk of complications.

Effect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia.

INTRODUCTION: The advent of tyrosine kinase inhibitors (TKIs) was revolutionary in the management of chronic myeloid leukemia (CML). Although TKIs were generally considered to be safe, they can be associated with renal injury. We evaluated the effect of TKIs on renal functions in a cohort of patients with long-term follow-up. MATERIAL AND METHODS: We retrospectively examined patients with chronic phase CML treated with TKIs. We analyzed the estimated glomerular filtration rate (eGFR) of patients from the initiation of TKI to the last follow-up. eGFR values of CML patients were compared to those of patients with stage 1 or 2 chronic kidney disease (CKD). RESULTS: A total of 195 patients with CML and 138 patients with CKD were examined. eGFR decline was 1.556 ml/min/1.73m2/year for patients with CML (P = .221). Patients receiving second-generation TKIs (2GTKI) were estimated to have 0.583 ml/min/1.73m2 higher eGFR value than that of the imatinib group, but it was not significant (P = .871). eGFR of patients who had used bosutinib had a downward trend. Duration of TKI therapy, age, and hypertension were found to be significant factors in eGFR decline for CML patients. Lower baseline GFR was associated with an increased risk of CKD development. CONCLUSION: Imatinib could result in a decline in eGFR which was clinically similar to early-stage CKD patients. We did not observe significant kidney function deterioration in patients receiving 2GTKIs including dasatinib and nilotinib. We recommend close renal function monitoring in patients receiving imatinib, especially for elderly patients with lower baseline eGFR and hypertension.

Ecthyma Gangrenosum-like Lesions in a Febrile Neutropenic Patient with Simultaneous Pseudomonas Sepsis and Disseminated Fusariosis.

UNLABELLED: Fusarium spp. is an opportunistic mold that causes disseminated infections in immunocompromised patients. It is important to make a definite diagnosis because of high mortality rates. We present the case of a 27-year-old pregnant woman diagnosed with acute myeloid leukemia with a prolonged febrile neutropenic period. She developed ecthyma gangrenosum-like lesions and simultaneously had Pseudomonas bacteremia and disseminated fusariosis. Histopathological and microbiological features of skin lesions had a critical role in differential diagnosis. Ecthyma gangrenosum-like lesions due to disseminated fusariosis might be easily misdiagnosed as lesions associated with Pseudomonas unless tissue cultures and histopathological examinations are performed. CONFLICT OF INTEREST: None declared.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients.

OBJECTIVE: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. MATERIALS AND METHODS: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. RESULTS: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. CONCLUSION: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. CONFLICT OF INTEREST: None declared.

Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil administered in relation to a liposuction procedure.

Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR.

Pulmonary radiological findings in patients with acute myeloid leukemia and their relationship to chemotherapy and prognosis: a single-center retrospective study.

OBJECTIVE: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Pulmonary are among the most common causes of mortality in AML. This single-center retrospective study aimed to evaluate the relationship between radiological findings of pulmonary at presentation and post chemotherapy on prognosis and clinical outcome in a group of AML patients. MATERIAL AND METHODS: The study included 278 AML patients. Clinical and radiological findings, laboratory findings, and microbiological culture results were evaluated. Pulmonary complications at presentation and post chemotherapy were compared. RESULTS: Pulmonary complications were observed in 53 of the patients (19%). Mean age of the patients with and without pulmonary complications was 43.1 ± 15.2 years and 38.8 ± 16.3 years, respectively (P < 0.001). Pulmonary complications were not correlated with gender, AML subtype, or the serum lactate dehydrogenase (LDH) level. The most common cause of pulmonary complications was infection. Pulmonary complications were observed in 29% and 71% of the patients at presentation and post chemotherapy, respectively. CONCLUSION: Pulmonary complications were observed more frequently at presentation in neutropenic AML patients of advanced age. The mortality rate was higher among the AML patients that had pulmonary complications at presentation.

The Association Between JAK2V617F Mutation and Bone Marrow Fibrosis at Diagnosis in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

OBJECTIVE: Bone marrow fibrosis is the second most common complication that causes morbidity and mortality inpatients with Philadelphia-negative myeloproliferative neoplasms (MPNs). The aim of this study was to investigate theassociation between JAK2V617F mutation and bone marrow fibrosis at diagnosis in patients with MPNs. MATERIAL AND METHODS: In total, 149 patients with MPNs were retrospectively evaluated to determine if there was anassociation between the histological grade of bone marrow fibrosis and JAK2V617F mutation. RESULTS: In all, 67.7% of the patients carried the mutated JAK2 gene. The presence of JAK2V617F mutation was notassociated with the occurrence of bone marrow fibrosis (P=0.55) or its grade at diagnosis (P=0.65). CONCLUSION: Molecular mechanisms or genetic defects other than JAK2V617F may underlie the occurrence of bonemarrow fibrosis in patients with MPNs.

Investigation of 13q14.3 deletion by cytogenetic analysis and FISH technique and miRNA-15a and miRNA-16-1 by real time PCR in chronic lymphocytic leukemia.

Background: The most frequent cytogenetic aberration is 13q14.3 deletion in Chronic Lymphocytic Leukemia (CLL). HsamiR-15a/hsa-miR-16-1 are tumor suppressor miRNAs encoded from 13q14.3 region. Objectives: The aim of this study was to investigate the 13q14.3 deletion using molecular and cytogenetic techniques and association with miRNA-15a/miRNA-16-1. Materials And Methods: We used peripheral blood samples of 30 CLL patients who were either induced and or non-induced with DSP30+IL-2 to determine 13q14.3 deletion by karyotyping and iFISH. Expression levels of hsa-miR-15a/miR-16-1 were measured using qRT PCR and compared with deletions. Results: 13q14.3 deletion was detected in 8.6% of cases by karyotyping and in 65% by iFISH. Mosaic forms (monoallelic+biallelic) were observed in 50% of cases. Besides determining common chromosome abnormalities such as add(2)(q37), t(2;7) (p11.2;q22), del(6)(q13q21), del(6)(q25), add(9)(q21), del(11)(q23), t(11;14)(q13;q32), del(13)(q11q12), del(13)(q12q14), add(14) (q23), del(14)(q23), t(14;19)(q32;q13.1), del(15)(q23), del(17)(p12), t(18;22)(q21;q11.2), add(21)(p13) and t(17;21)(q11.2;122), we also determined t(1;13)(q32;q34), inv(2)(p25q21), del(13)(q22q32), t(14;19)(q24;q13), dup(17)(q21q23), der(21;21)(p13;p13) which have not been reported previously. Mitotic index data was found statistically significant and DSP30+IL-2 increased mitotic index by 2.5 folds. Association between decreased miR-16-1 expression and deletions was statistically significant. Conclusion: We suggest that cytogenetic and iFISH analyses are complementary and use of DSP30+IL-2 is effective .in CLL. Decreased expression of hsa-miR-16-1 is remarkable.