Mahmut Töbü

Augmentation of methylprednisolone-induced differentiation of myeloid leukemia cells by serine/threonine protein phosphatase inhibitors

To elucidate the roles of serine/threonine protein phosphatases type 1 (PP1) and type 2A (PP2A) in methylprednisolone-induced differentiation of HL60 cells into granulocytes and K562 cells into monocytes, we examined the effect of serine/threonine protein phosphatase inhibitors, okadaic acid and Cal-A on the proliferation/differentiation of HL60 and K562 cells. Okadaic acid and Cal-A augmented methylprednisolone induced granulocytic differentiation and cell death of HL60 cells and monocytic differentiation and cell death of K562 cells in different dose ranges, respectively. These data suggest an important role of PP1 and PP2A in the mechanism leading to differentiation of leukemic cells.

Progressive Transformation of Germinal Centers: Single-Center Experience of 33 Turkish Patients

Progressive transformation of germinal centers (PTGCs) is a benign disease of the lymph nodes that is rarely associated with Hodgkin disease. We reviewed the clinical and pathologic features of PTGCs and the relationship of PTGCs with lymphoid neoplasia in an adult population. The data from 33 patients who were diagnosed with PTCGs were retrospectively analyzed. Of the 33 PTGC patients, 48.5% were men and 51.5% were women, with a mean age of 43.8 years at diagnosis. Most of the enlarged and excised lymph nodes were cervical and axillary. Diffuse large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma was detected concurrent with PTGC in 2 patients. Also, PTGCs was detected 3 years after the diagnosis of diffuse large B-cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and T-cell-rich B-cell lymphoma in 3 patients. No relapse was found in the patients with lymphoma, and no progression to lymphoma was detected during the follow-up of the other patients. PTGCs is not considered a premalignant entity; however, the development of lymphoma has been reported rarely. If PTGCs occurs in the follow-up process of patients with lymphoma, the follow-up intervals should be shortened.

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.

Carfilzomib experience in relapsed/refractory multiplemyeloma: 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.

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 (1–4); 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.

Report On Three Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive tumor that was classified as a distinct entity among myeloid neoplasms in the World Health Organization’s 2016 revision of the classification of acute myeloid leukemia and related neoplasms. Most patients present with cutaneous lesions with or without bone marrow involvement and leukemic dissemination. The tumor cells express CD4, CD56, CD123, and TCL1 [1]. In general, acute lymphocytic leukemia (ALL)/ lymphoma-type regimens were reported to show better survival outcomes than acute myeloid leukemia (AML)-type regimens. Complete remissions were registered for 7 of 26 patients after AML-type regimens and 10 of 15 patients after ALL/lymphomatype regimens, with a significant advantage for the ALL/ lymphoma-type approach [2,3]. Patients who were treated with hyper-CVAD showed an objective response, but the duration of response was short so hematopoietic stem cell transplantation (HSCT) should also be considered [4]. Recent interest has been directed towards SL-401, a novel immunotherapy directed at IL-3R, notably overexpressed in BPDCN as well as other myeloid malignancies. This led to the development of SL-401 as an IL3-diphtheria toxin conjugate that has demonstrated promise for BPDCN in early-phase trials [5,6,7,8]. We aim to share our experience with BPDCN due to its rareness and the lack of a consensus about treatment.

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.

Cauda equina involvement in newly diagnosed myeloma patient

Cauda Equina Syndrome (CES) is a rare complication of Multiple Myeloma (MM) that is a clonal plasma cell disorders. We presented a case who newly diagnosed MM which complicated with cauda equina involvement. A 51-year-old woman admitted to our hospital because of weakness and low back pain. Neurological examination demonstrated sphincter dysfunction, decreased Achilles tendon reflexes, frust hemiparesia, reflected CES. Laboratory analysis was revealed anemia, hipergammaglobulinemia and monoclonal peak in the protein electrophoresis. Magnetic resonance imaging (MRI) of the spine showed multiple vertebral compression fractures and marked contrast enhancement of the cauda equina region. The patient was diagnosed MM with bone marrow biopsy. After VAD treatment, MRI showed disappearance of infiltration. Although, there are some case reports with cauda equina involvement in myeloma patient, we could not find any case presenting with CES in newly diagnosed MM. This rare complication should be remembered in myeloma patients who presented symptoms of CES.

Risk factors for poor mobilization in solid tumors: How effectively can we mobilize patients with solid tumors?

BACKGROUND In the literature, risk factors for poor mobilization were tried to identify. However, most of the studies consisted heterogeneous group of patients including both hematologic and oncologic malignancies. In this study, we aimed to identify the risk factors for poor mobilization in adults with solid tumors. METHODS We enrolled 49(47 men, 2 women) adult patients with solid tumor who were mobilized between September 2007 and February 2017. All the mobilization procedures were performed with G-CSF(10μg/kg/day) with chemotherapy. Mobilization insufficiency was defined as peripheral blood CD34+stem cell number less than 10/μl and/or total collected CD34+cells less than 2.5×10 6/kg. RESULTS The patients were divided into two groups, patients with successful mobilization at the first attempt(group 1, 36 patients,73.5%) and poor mobilizers (group 2, 13 patients 26.5%). Second and third mobilization attempt was needed in 11 and 2 patients, respectively. The median number of CD34+cells collected was 7,08×106/kg(0,6-19) with a median 4(1-6) apheresis. There was no statistical difference between two groups in terms of patients and mobilization characteristics. Only number of CD 34+stem cells collected was statistically different (median 9,07×106/kg CD34+cells in group 1 versus 2,14×106/kg in group 2, p<0.05). The only possible risk factor that we could define was presence of organ metastasis. CONCLUSIONS Since several methods and new drugs are available for peripheral stem cell collecting, risk factors should be identified clearly in adult population with solid tumors. So multicenter studies should be constructed for resolving this problem.