Clinicopathological characteristics, genetics and prognosis of patients with myeloid sarcoma: a single-center study.

AIM: Myeloid sarcoma (MS) is a rare tumour comprising myeloid blasts occurring at an anatomical site other than the bone marrow. We sought to investigate both paediatric and adult patients with MS diagnosed at our institution and determine possible correlations among their clinicopathological, phenotypic, molecular and prognostic features. METHODS: This study retrospectively evaluated the data of 45 patients diagnosed with MS at Ege University Faculty of Medicine Hospital, Turkey, over a 17-year period. RESULTS: The male-to-female ratio was 1.5:1, and the median age was 39.12 years. The most commonly involved sites were the skin, lymph nodes, soft tissues and bone. Immunohistochemically, CD68-KP1 was the most commonly expressed marker, followed by CD33, myeloperoxidase, CD117, lysozyme, CD68-PGM1 and CD34. Of the patients, 26 (57.7%) presented with de novo MS, 7 (15.5%) had simultaneous acute myeloid leukaemia and 12 (26.8%) had a previous history of haematological disorders. Kaplan-Meier survival analysis revealed that the 2-year and 5-year overall survival (OS) rates were 46.4% and 39.8%, respectively; the median OS duration was 11 months. Increasing age had a negative prognostic relationship with survival (p = 0.04). Chromosomal abnormalities were detected in approximately 6/10 (60%) of paediatric patients and 6/9 (66.7%) of adult patients. t(8;21)(q22;q22) translocation was identified in 20% of paediatric patients. CONCLUSIONS: MS diagnosis is usually challenging; an expanded immunohistochemical panel should be used for an accurate diagnosis. Although MS generally has a poor prognosis, increasing age appears to be associated with a worse outcome.

The effect of serum lipid levels on peripheral blood hematopoietic stem cell levels.

INTRODUCTION: There are limited numbers of available retrospective studies on various hematological diseases treated with stem cell mobilization therapy. In the present study, we aimed to demonstrate the effects of serum lipid levels on peripheral blood CD34+ (PBCD34+) cell counts as well as the changes in serum lipid levels during stem cell mobilization process. METHOD: PBCD34+ cell counts were compared between hypercholesterolemic patients and healthy individuals. Additionally, total cholesterol (TChol), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglyceride (TG) levels were measured from healthy donors who underwent stem cell mobilization, at different time points (prior to filgrastim [phase 1], prior to apheresis [phase II], and the first week following apheresis [phase III]. RESULTS: In the hypercholesterolemia group, the PBCD34+ cell count was found to be higher among patients with elevated LDL-C (2.6 ± 0.35/µL vs. 1.7 ± 0.17/µL, p = 0.003) and TChol (2.6 ± 0.34/µL vs. 1.7 ± 0.14/µL, p = 0.006) in comparison to the healthy controls. In the mobilization group, phase II HDL-C levels (35.3 ± 2.8 mg/dL) were found to be lower than both phase I (45.6 ± 2.1 mg/dL) and phase III (44.5 ± 2.6 mg/dL) (p = 0.007). Phase II TChol levels (183.5 ± 10.0 mg/dL) were lower than both phase I (216.8 ± 8.5 mg/dL) and phase III (212.2 ± 8.4 mg/dL) (p = 0.02). At phase II, there was an inverse correlation between PBCD34+ cell count and HDL-C (r = - 0.57, p = 0.003). DISCUSSION: Our results indicate that, while increased LDL-C level is the determinant of baseline PBCD34+ cell count, reduced HDL-C is the determinant of PBCD34+ cell count during mobilization process.

Role of Allogeneic Stem Cell Transplant in the Treatment of Primary Myelofibrosis.

OBJECTIVES: The only known curative therapy for primary myelofibrosis is allogeneic hematopoietic stem cell transplant. MATERIALS AND METHODS: We retrospectively evaluated 11 transplant procedures involving 10 patients (5 men and 5 women) diagnosed with primary myelofibrosis between 2005 and 2014. RESULTS: The median age at the time of transplant was 60.5 years (range, 22-62 years). Stem cell sources were unrelated (n=1) and related (n=11) peripheral blood stem cells. Conditioning regimen was myeloablative for 8 and reduced intensity for 3 transplants. The median number of infused CD34+ cells was 6.8 × 106 cells/kg (range, 3.2-10.4 × 106 cells/kg). Neutrophil and platelet engraftment occurred at median of 22 days (range, 12-31 days) and 19.5 days (range, 13-56 days). Acute and chronic graft-versus-host disease was seen in 4 of 11 allografts. Relapse and nonrelapse mortality rates were 20%. Six patients (60%) were still alive without disease after median follow-up of 68.5 months (range, 17-120 months). Median progression-free survival and overall survival were 61 months (range, 2-120 months) and 65 months (range, 2-120 months). CONCLUSIONS: Our results suggest that allogeneic hematopoietic stem cell transplant may provide a curative treatment for primary myelofibrosis patients. A myeloablative regimen seems to be effective and safe, especially for younger primary myelofibrosis patients.

Efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/ refractory multiple myeloma: a real-life experience

Background/aim: In Turkey, lenalidomide plus dexamethasone (RD) has been used to treat relapsed/refractory multiple myeloma (RRMM) since 2010. This retrospective, single-center study evaluated the efficacy and tolerability of RD in patients with RRMM between October 2010 and June 2016. Materials and methods: Patients' records were reviewed, and overall (OS) and progression-free survival (PFS) were assessed. Results: One hundred and twenty patients (71 males; 59.2%) were included in the study. The median number of prior lines of treatment was one (1­4); 72 patients (60.0%) received RD as second-line therapy and 51 patients (42.5%) had previously undergone autologous stem cell transplantation (ASCT). The overall response rate was 72.5%, with 19% of these patients achieving a complete response. The median length of follow-up and duration of response to RD was 14 months and 19 months, respectively. Median OS and PFS were 32 and 21 months, respectively. Prior ASCT, an overall response, and treatment with RD for >12 cycles were identified as independent prognostic factors for OS and PFS. Adverse events (AEs) occurred in 69 (57.5%) and 14 patients (11.7%) discontinued treatment due to AEs. Conclusion: We found RD to be safe, well tolerated, and effective in RRMM in everyday clinical practice in Turkey.

A Retrospective Comparison of TECAM and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplant in Lymphoma Patients: Efficacy and Toxicity.

OBJECTIVES: The aim of our study was to evaluate the efficacy and toxicity of TECAM (thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan) and BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimens before autologous hematopoietic stem cell transplant in patients with lymphoma. MATERIALS AND METHODS: We retrospectively analyzed 108 relapsed/refractory lymphoma patients who had high-dose treatments followed by autologous hematopoietic stem cell transplant between October 2012 and February 2017. RESULTS: At a median follow-up period of 16 months, the estimated 2-year progression-free survival rates for the TECAM and BEAM groups were 55.7% and 52.9%, respectively (P = .811). The estimated 2-year overall survival rate in the TECAM group (55.9%) was relatively inferior to that shown in the BEAM group (67%), but the differences were not significant (P = .238). No differences were observed for time to hematopoietic recovery and duration of hospitalization. Incidences of transplant-related infectious and noninfectious complications were similar for each conditioning regimen. CONCLUSIONS: Our experience shows that the TECAM regimen is an effective high-dose chemotherapy for lymphoma patients before autologous hematopoietic stem cell transplant.

Carfilzomib experience in relapsed/refractory multiple myeloma: a single-center experience

Background/aim: Carfilzomib (CFZ) is a new-generation proteasome inhibitor with significant activity in relapsed or refractory multiple myeloma (R/R-MM). We have retrospectively evaluated R/R-MM patients who were treated with CFZ plus dexamethasone. Materials and methods: Twenty-one R/R-MM patients who were treated with CFZ plus dexamethasone between October 2013 and January 2016 were screened. The patients were followed until March 2016 after CFZ treatment. Results: Ten (47.6%) of the patients were female and 11 (52.4%) of them were male. The median age was 62 (47-76) years. The median number of prior treatment lines was 3 (2-7). The median number of administered cycles of treatment for CFZ was 4 (1-10). The median overall response rate was 26.3%. The most common hematological adverse events were anemia and thrombocytopenia (38%). The most common nonhematological adverse event was fatigue (71.4%). One patient died because of a cerebrovascular event and 1 patient died because of pneumonia during the treatment period. The median duration of response rate and time to next therapy were 8 (7-9) and 3 (2-16) months, respectively. The median overall survival was 8 (0.5-33) months. Conclusion: Despite the small number of patients, our results suggest that CFZ provides acceptable responses in heavily pretreated R/R-MM patients.

Epidemiology and analysis of invasive fungal infections in patients withhematological malignancies: a single-center real-life experience

Background/aim: Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies. We evaluated the incidence and treatment characteristics of IFIs between October 2012 and December 2013. Materials and methods: Patients who received chemotherapy or stem cell transplantation were retrospectively evaluated. Fungal infections were classified according to EORTC criteria.Results: Prophylaxis and antifungal therapy were given in 30.5% and 23.6% of 522 chemotherapy courses, respectively. The incidence of proven/probable IFI was 6.7%. The incidence of IFI among patients who received prophylaxis was significantly higher than among those who did not receive it (11.3% vs. 4.6%, P = 0.005). There was no significant difference between patients who received mold-active and no mold-active prophylaxis (P = 0.098). The most common single agent therapy and causative pathogen was liposomal amphotericin B (57.1%) and Aspergillus (n = 5), respectively. IFI-attributable mortality rate was 14.2% in 6 weeks.Conclusion: The IFI incidence and mortality rate were similar to that reported in the literature. The IFI rate was higher in the group using prophylaxis, as this is a high-risk group. Although the IFI rate was not significantly different between groups using prophylaxis, patients should be followed closely for the effective use of posaconazole prophylaxis.

Retrospective analysis of primary gastric diffuse largeB-cell lymphoma: a single center study from Turkey.

BACKGROUND/AIM: Diffuse large B-cell primary gastric lymphomas (DLBC-PGLs) are treated with different therapies. Their optimal treatment is not well documented. MATERIALS AND METHODS: We retrospectively analyzed the data of 51 patients diagnosed with DLBC-PGL in the previous 10 years. All patients were treated with R-CHOP as first line. Radiotherapy was added to chemotherapy in 8 patients. Surgery was performed in 5 patients. RESULTS: The median follow-up time of the 51 patients was 45.5 (range 5-144) months and the complete response (CR) rate was 90.2%. CR was achieved in 34 (89.4%) of 38 patients treated with single chemotherapy, in all (100%) 5 patients treated with chemotherapy plus surgery, and in 7 (87.5%) of 8 patients treated with chemotherapy plus radiotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 85.8% and 89.6%, respectively. The 5-year OS and EFS rates were not significantly different between patients treated with single chemotherapy or chemotherapy plus radiotherapy/surgery (P > 0.05). CONCLUSION: R-CHOP chemotherapy is as effective as R-CHOP plus radiotherapy/surgery in the treatment of DLBC-PGL patients. Prospective randomized large cohort studies are needed to generate guidelines for the treatment of DLBC-PGL.

Cholesterol Levels in Patients with Chronic Lymphocytic Leukemia.

Low cholesterol levels may be accompanied by solid tumors or hematological malignancies such as multiple myeloma. Decreased cholesterol levels have been reported in some experimental studies about chronic lymphocytic leukemia (CLL). It may be associated with tumoral cell metabolism. Herein, we examine blood lipid profiles of patients with newly diagnosed CLL (284 male, 276 female, mean age 64 ± 11 years) as defined by National Cancer Institute criteria. The control group consisted of 71 healthy subjects with mean age 55 ± 9 years (28 male, 43 females). 60% of patients with Binet A, while 25% were Binet C. Decreased levels of total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) were observed in patients with CLL than control group (p < 0,001). There was no statistical significance between CLL and control group for triglycerides (TG) and very low density lipoprotein (VLDL), also between HDL-C, VLDL, TG and grades. Cholesterol may metabolized by abnormal lymphocytes in CLL patients.

Ocular Adnexal Lymphomas: Single-Center Experience.

Ocular adnexal lymphoma (OAL) is a rare manifestation of non-Hodgkin lymphoma consisting of the tissues and structures surrounding the eye that include the conjunctiva, eyelids, lacrimal gland, and orbital soft tissues. OAL comprise 1% to 2% of all non-Hodgkin lymphomas and about 8% of the extranodal lymphomas; however, the incidence of OAL has increased by approximately 6% annually in last 2 decades, and OAL now represents the majority of orbital malignancies. There are no uniform treatment guidelines for OAL. Because of high local and extraorbital recurrence rates, appropriate local, systemic, or combined treatment must be applied.

Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience.

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. MATERIALS AND METHODS: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. RESULTS: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. CONCLUSION: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events.

Evaluation of immunomodulatory drugs in multiple myeloma: single center experience.

OBJECTIVE: Multiple myeloma (MM) comprises 1% of all cancers and 10% of hematologic malignancies and known as an incurable disease. The introduction of immunomodulatory drugs (IMiDs) has brought a major shift in therapeutic paradigm in the treatment of newly diagnosed and relapsed/refractory MM patients. The aim of this study was to evaluate the relationship between response status and hematological parameters in patients with MM treated with thalidomide or lenalidomide. METHODS: Sixty-eight patients who were treated with IMiDs in Ege University, School of Medicine, Department of Hematology, between 2005 and 2012, were evaluated, retrospectively. RESULTS AND CONCLUSION: We could not find any difference between the hematological parameters before and after the treatment neither with thalidomide nor lenalidomide. However, the heterogenity of our groups, the difference in treatment strategies and potential side effects would have an impact on this result. It is needed to perform prospective clinical trials to prove that whether correction of hematological parameters would reflect the response status in patients with myeloma that treated with IMiDs.

The loss of CD34+ cells in peripheral hematopoietic stem cell products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage.

Although peripheral blood stem cell (PBSC) products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage are used frequently, data regarding the rate of loss of CD34+ cells in these products are limited. In this prospective study, CD34+ cells were counted at three (fresh, post-overnight and post-thaw) points in 83 PBSC products from 41 patients by flow cytometry. Compared to fresh products, the mean losses of post-overnight and post-thaw total CD34+ cells are 16.3% and 38.4% (p = 0.02), and the mean losses of post-overnight and post-thaw viable CD34+ cells are 16.5% and 48.5%, respectively (p < 0.001). The numbers of fresh viable, post-thaw total and post-thaw viable CD34+ cells were inversely correlated with the durations of neutrophil and platelet engraftment. Our results indicate that the mean loss of post-thaw total and viable CD34+ cells is approximately 20% higher than that observed in standard cryopreservation methods. In addition, fresh viable, post-thaw total and especially post-thaw viable CD34+ cell levels are valuable predictors of both neutrophil and platelet engraftments.

CD31 expression on peripheral blood stem cells predicts both early neutrophil and platelet engraftments.

No detailed information currently exists about the immune phenotypic profiles of peripheral blood stem cells (PBSCs) obtained by different mobilization regimens. The effects of these profiles on the outcome of transplantation are largely unknown. In this prospective study, the surface immune phenotypic features (CD11a, CD18, CD31, CD38, CD44, CD62e, CD62L, CD90, CD117, CD135 and CD184 expression) of sorted PBSCs that had been mobilized by growth factor with (group I and group II) or without (group III) disease-specific chemotherapies were investigated. The immune phenotypic features on mobilized PBSCs in groups I, II and III were not significantly different. The CD31 (platelet endothelial cell adhesion molecule-1) positivity ratio on PBSCs inversely correlated with both the duration of neutrophil (r=-0.32, p=0.03) and platelet (r=-0.36, p=0.02) engraftment. No relationship was found between the engraftment (neutrophil and platelet) durations and CD184 (chemokine receptor CXC motif receptor 4 [CXCR4]) expression on PBSCs. We demonstrated that the surface immune phenotypic profiles on PBSCs obtained by several mobilization regimens were not different. To our knowledge, this is the first study to demonstrate that CD31 expression on human PBSCs may positively affect both neutrophil and platelet engraftment. Contrary to our expectations, CD184 (CXCR4) expression on PBSCs has no effect on neutrophil or platelet engraftment. Considered together, our results suggest that additional surface antigens (such as CD31) may be more effective in the homing process.

Risk factors for a poor hematopoietic stem cell mobilization.

Poor mobilization is an important problem in autologous stem cell transplantation. We retrospectively reviewed the data of 165 mobilized patients to identify possible risk factors for a poor stem cell mobilization. 27 patients (16.4%) were categorized as poorly mobilized. The poor mobilization ratio differed according to diagnosis (lymphoma: 25.4%, acute leukemia: 15.4%, amyloidosis: 14.3%, and multiple myeloma: 9.6%). Being diagnosed as lymphoma (odds ratio [OR]=6.02, p=0.001), advanced age (OR=1.05, p=0.007) and increased weight (OR=1.03, p=0.03) were found as possible risk factors. Being diagnosed as lymphoma was shown to be the most important risk factor for a poor mobilization. Leukapheresis staff should be aware of the increased risk of a poor mobilization in lymphoma patients and remobilization methods should be considered from the beginning.

The clearance time of infused hematopoietic stem cell from the blood circulation.

There is no detailed information about the clearance time of infused hematopoietic stem cell (HSC) from the blood circulation in humans. In this prospective study, peripheral blood CD34+ cell counts were detected during the 4days period following autologous HSC transplantation in 20 patients by means of flow cytometry. The median CD34+ cells were at the highest level in the first hour and decreased below pre-infusion values on the first day after HSC infusion. By nonparametric analysis, positive correlation was found between CD34+ cell levels at the first hour and the post-thaw CD34+ cell dose (r=0.57, p=0.01). An inverse correlation was determined between CD34+ cell levels at the first hour and neutrophil engraftment (r=-0.54, p=0.01). Compared with the patients having CD34+ cell count of ⩾2µL(-1) in the first hour following HSC infusion, the patients having CD34+ cell count of <2µL(-1) had delayed both neutrophil (20 vs. 12, p=0.008) and platelet (47 vs. 11, p=0.01) engraftments. Our results indicated that infused HSCs were removed from the blood circulation within 1day. In addition, CD34+ cell levels at the first hour may be used as an important indicator to predict the delay of neutrophil and platelet engraftments.

The difference in lactate dehydrogenase activity between pre- and post-mobilization periods is a good indicator of successful stem cell mobilization.

Predicting poor stem cell mobilization may prevent the costs and complications associated with remobilization. We retrospectively reviewed the relationship between serum lactate dehydrogenase (sLDH) activity and peripheral blood CD34 (PBCD34) cell counts in 46 granulocyte colony stimulating factor (G-CSF) induced mobilization cycles with or without chemotherapy. A significant correlation between post-mobilization (pre-apheresis) sLDH activity and PBCD34 count was found (r(s)=0.43, p=0.007). A strong correlation was shown between the pre- and post-mobilization sLDH activity difference and PBCD34 count (r(s)=0.55, p=0.001). With respect to sLDH activity differences; (a) all patients with a difference of >300 U/L, (b) 71% of patients with a difference of 100-300 U/L, and (c) 44% of patients with a difference of <100 U/L were considered to have good mobilizations. The sLDH activity difference between pre- and post-mobilization is a good indicator of successful mobilization. According to our results, the success of mobilization can be predicted based on sLDH activity differences; (i) good mobilization if the difference is >300 U/L, (ii) intermediate risk if the difference is 100-300U/L, and (iii) high risk if the difference is <100 U/L.

Molecular analysis and clinical findings of Griscelli syndrome patients.

Griscelli syndrome (GS) is a rare autosomal recessive disorder associated with skin or hair hypopigmentation, hepatosplenomegaly, pancytopenia, and immunologic and central nervous system abnormalities. GS type II is caused by RAB27A mutations. We present RAB27A mutation analysis of 6 cases diagnosed as GS type II. Missense mutations (L26P and L130P) in 2 cases, deletion of 5 bases (514delCAAGC) in 2 cases, and 1 base deletion (148delA) in 2 cases were detected. This report has importance in phenotype-genotype correlation of different types of mutations including missense mutations and deletions within the RAB27A gene in GSII syndrome.

Plerixafor use in patients with previous mobilization failure: A multicenter experience.

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.

Acquired activated protein C resistance in sarcoma patients.

Acquired activated protein C resistance (aAPCR) is seen more frequently in solid and hematological cancer patients. We aimed to investigate the presence of aAPCR and the frequency of clinically detectable thrombosis in sarcoma patients. Normalized activated protein C sensitivity ratio (nAPCSR), factor V Leiden (FVL) mutation, factor V (FV) levels and factor VIII (FVIII) levels were prospectively measured in 52 patients and in 52 healthy controls. Clinically detectable thrombosis was present in one patient (1.92%). Compared with healthy controls (106%), the sarcoma patients had significantly lower values of the nAPCSR at pre (87.25%) and post (94.35%) treatment period (P < 0.0001). aAPCR was found as 4.2, 13 and 0%, respectively. The post-treatment FV levels (178.1 U/dl) were significantly (P < 0.001) higher than the pretreatment levels (147.5 U/dl). Inverse correlation was found between post-treatment FV levels and nAPCSR values (r = -0.38, P < 0.02). We found out a slightly increased frequency of venous thromboembolism in sarcoma patients. As an original finding which has not been reported previously in the literature, we also found out a decrease in the nAPCSR, persisting even after treatment. Thirdly, we found out that the significantly higher rate of aAPCR at the time of diagnosis totally disappeared after treatment.