Molecular evaluation of mutations in acute myeloid leukemia patients from Turkey: A single-center study.

ABSTRACT: Certain genetic mutations could have a role in the etiology of acute myeloid leukemia (AML). Hereby, in this study, we primarily aimed to investigate the distribution of genetic mutations in AML patients. We also attempted to analyze the incidence of genetic mutations in AML patients from Turkey.This retrospective study included a total of 126 patients diagnosed with AML, who had molecular mutation test results or records in their patient files. The patients who were not citizens of the Republic of Turkey were not included in the study.It was observed that analyses for at least 1 c-kit exon mutation had been carried out on 76 patients, which detected no c-kit mutation among the types of genetic mutations investigated in all of those 76 patients. We found the frequency of FMS-like tyrosine kinase 3-internal tandem duplication mutation as 25%. The prevalence of translocation(15;17) was approximately 11% and the prevalence of translocation(8;21) was % 6.25. In addition, we also showed that the frequency of inversion16 was nearly 3.7%.Lastly, the possibility of c-kit mutation in AML patients from Turkey might actually be low.

Analysis of pre-chemotherapy WBC, PLT, monocyte, hemoglobin, and MPV levels in acute myeloid leukemia patients with WT1, FLT3, or NPM gene mutations.

Effects of mutations on AML (acute myeloid leukemia) patients have been an area of clinical interest. The aim of this study was to analyze pre-chemotherapy WBC (white blood cell), platelet, monocyte, hemoglobin, and mean platelet volume (MPV) levels in acute myeloid leukemia patients with Wilms tumor 1 (WT1), FMS-like tyrosine kinase 3 (FLT3), or nucleophosmin (NPM) gene mutations, attempting to detect and compare possible differences in these values.The study included 71 patients with acute myeloid leukemia known to have WT1, FLT3, or NPM gene mutations. The patients were divided into 3 groups: FLT3-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 1), NPM-mutated AML patients without any accompanying known mutations other than WT1 at the time of diagnosis (Group 2), WT1-mutated AML patients with no other accompanying known mutations at the time of diagnosis (Group 3). We carried out intergroup comparisons of WBC, platelet (PLT), monocyte, hemoglobin, and MPV levels before chemotherapy.There was a statistically significant difference between the groups in terms of WBC parameters (P = .001). There were no statistically significant differences between the groups with respect to hemoglobin, platelet, and monocyte levels.Higher white blood cell counts could be observed in patients with FLT3-mutated AML.

The effect of gemcitabine, dexamethasone, and cisplatin chemotherapy in relapsed/refractory NHL and HL patients: A single center experience.

The optimal choice of salvage therapy for patients with relapsed/refractory non-Hodgkin lymphoma or Hodgkin lymphoma remains controversial. In this study, we aimed to share our experience in relapsed/refractory lymphoma patients who received GDP/R-GDP as salvage chemotherapy in our center. Data of 47 relapsed/refractory Hodgkin lymphoma and non-Hodgkin lymphoma patients who received GDP or R-GDP as salvage chemotherapy in our center between July 2014 and October 2017 were retrospectively evaluated. Non-Hodgkin lymphoma and Hodgkin lymphoma patients were divided into two groups as primary refractory and relapsed. The one-year overall survival was 100% (for relapsed) and 36.9% (for refractory) in the non-Hodgkin lymphoma groups, and 82.5% (for relapsed) and 80% (for refractory) in the Hodgkin lymphoma group. The one-year progression-free survival (PFS) was 72.7% (for relapsed) and 38.5% (for refractory) in patients with NHL, and 41% (for relapsed) and 18.2% (for refractory) in patients with HL. GDP/R-GDP seems to be a well-tolerated out-patient salvage regimen for relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma. Although proven efficacy, negative toxicity profile, and ease of administration, the application of gemcitabine-based therapy for patients with primary refractory non-Hodgkin lymphoma and Hodgkin lymphoma provided limited success.

Evaluation of neutropenia-related outcomes in Hodgkin's lymphoma patients with moderate or severe neutropenia who received ABVD chemotherapy without using granulocyte-colony stimulating factor.

OBJECTIVE: To evaluate the possible neutropenia-related effects of administering adriamycin [doxorubicin], bleomycin, vinblastin, dacarbazine (ABVD) chemotherapy in Hodgkin's lymphoma patients with moderate or severe neutropenia without granulocyte-colony stimulating factor supplementation. METHODS: This study evaluated neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use during the periods between chemotherapy rounds. Forty-three rounds of ABVD chemotherapy were evaluated in the study. The outcomes that could be related to neutropenia were analyzed. In addition, rounds of ABVD chemotherapy given in the presence of severe neutropenia were compared with ABVD chemotherapy rounds given in the presence of moderate neutropenia in terms of neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use. The study only included patients with classical Hodgkin's disease (lymphoma). Patients with a final neutrophil count of <1 × 103 cells/µL (<1000 cells/µL) prior to chemotherapy round and those receiving ABVD chemotherapy for Hodgkin's lymphoma were included in the study. RESULTS: We observed that none of the patients with moderate neutropenia before the start of chemotherapy round needed granulocyte-colony stimulating factor, and four patients with severe neutropenia prior to the start of chemotherapy round required granulocyte-colony stimulating factor. However, there was no statistically significant relationship between the severity of neutropenia (in terms of moderate and severe) before chemotherapy and granulocyte-colony stimulating factor requirement after chemotherapy (p> 0.05). Furthermore, none of the patients included in the study had bleomycin-related lung toxicity during the treatment periods included in the study. CONCLUSION: Administering ABVD chemotherapy to patients with moderate neutropenia seems to be safe.

Biosimilar filgrastim (leucostim®) have similar efficacy in steady-state hematopoietic progenitor cell mobilization compared to original filgrastim (neupogen®) and lenograstim (granocyte®): A retrospective multicenter study.

Biosimilar filgrastim (Leucostim®) was shown to be similar in terms of efficacy and safety in hematopoietic progenitor cell mobilization (HPCM) compared to originator filgrastim (Neupogen®) and lenograstim (Granocyte®) in healthy donors and chemomobilization settings. Here we report our retrospective experience with Leucostim® (n: 43) compared to Neupogen® (n: 71) and Granocyte® (n: 32) in steady-state mobilization of patients presenting with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma. The median age of patients on Leucostim® (56) arm was significantly higher compared to patients who received Neupogen® (50) and Granocyte® (49) (p: 0.039). Patients who underwent HPCM with Leucostim® received less chemotherapy lines (p: 0.026) and courses (p: 0.046) compared to others. Otherwise the study cohort was homogenous in terms of gender, primary diagnosis and various risk factors for mobilization failure. Mobilization failure was defined as failure to achieve a minimum threshold (10/µL) for peripheral blood CD34+ cell concentration to initiate leukapheresis or 0.5×106/kg, 0.8×106/kg and 2×106/kg CD34+ cells in first, second and fourth days of apheresis, respectively. The study groups were similar in terms of median number of CD34+ progenitor cell yield (×106/kg) (Neupogen®: 6.18, Granocyte®: 6.2 and Leucostim®: 6.2) (p: 0.959) and median number of leukapheresis sessions (p: 0.615). The treatment arms were also similar in terms of mobilization failure (Neupogen® 11.3% - Granocyte® 21.9% - Leucostim® 16.3%; p: 0.366). No patient experienced any severe adverse effect during HPCM. Leucostim® is equally effective and safe in HPCM compared to originator G-CSF (Neupogen®) and lenograstim (Granocyte®) in steady-state HPCM setting.

Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Daily Practice: A Multicenter Experience.

BACKGROUND: The prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph(+) ALL) is generally poor. Currently, allogeneic hematopoietic cell transplantation (allo-HCT) is the only accepted therapy with curative potential. PATIENTS AND METHODS: Herein, we report our multicenter, retrospective experience with 46 (23 female; 23 male) Ph(+) ALL patients, who were treated off-study between 2005 and 2012. RESULTS: The median age of the patients was 46 years (range, 19-73 years). During induction, 30 (65%), 13 (28%), and 3 (7%) patients received tyrosine kinase inhibitors (TKIs) concurrent with chemotherapy (TKIs/chemotherapy), chemotherapy only, and TKIs only, respectively. Following induction, rates of complete remission (CR) of the study population were 85% (n = 39). CR rate in patients receiving TKIs during induction (n = 33) was significantly higher compared with patients who received chemotherapy only (n = 13; P = .011). Taking TKIs during induction significantly reduced induction mortality (3.3% vs. 38%; P = .01). Allo-HCT was performed subsequently in 21 (46%) patients. More patients who received TKIs with or without chemotherapy (19/33; 58%) during induction were able to undergo to allo-HCT compared with patients who received chemotherapy only (2/13; 15%; P = .005). Median overall survival of patients who were treated with TKIs during induction and received allo-HCT (not reached; NR) was significantly prolonged compared with patients who received allo-HCT but without TKIs during induction (23.2 months) and to the rest of the cohort (21.2 months; P = .019). CONCLUSIONS: Current state-of-the art management of Ph(+) ALL in real-life seems to be incorporation of TKIs to chemotherapy regimens and proceeding to allo-HCT, whenever possible.

Finding the Optimal Conditioning Regimen for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation: A Retrospective Comparison of BEAM and High-Dose ICE.

OBJECTIVE: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHCT) is a well-defined treatment modality for relapsed/refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Although there are several options in terms of conditioning regimens before AHCT, no one treatment is accepted as a standard of care. This study aimed to compare different conditioning regimens for the treatment of NHL and HL. MATERIALS AND METHODS: Medical records of 62 patients who had undergone AHCT following BEAM (BCNU, etoposide, cytarabine, and melphalan) and high-dose ICE (hICE; ifosfamide, carboplatin, and etoposide) conditioning regimens were analyzed retrospectively and compared in terms of efficacy and adverse effects. RESULTS: The study included a total of 29 and 33 patients diagnosed with relapsed/refractory NHL and HL, respectively. Patients received BEAM (n=37) or hICE (n=25) regimens for conditioning. One-year overall survival was 73±6% in all patients. One-year overall survival was 71±8% and 74±9% in the BEAM and hICE groups, respectively (p=0.86). The incidences of nausea/vomiting (grade ≥2) (84% vs. 44.7%; p=0.04) and mucositis (grade ≥2) (13% vs. 3%; p=0.002) were higher in the hICE group compared to the BEAM group. In addition, we witnessed significantly more hepatotoxicity of grade ≥2 (40% vs. 2.7%; p<0.005) and nephrotoxicity of grade ≥2 (48% vs. 2.7%; p<0.005) among patients who received hICE. Significantly more patients (n=4; 25%) in the hICE group experienced veno-occlusive disease (VOD) compared to the BEAM arm, where no patients developed VOD (p=0.01). CONCLUSION: There was no difference in terms of overall survival between the BEAM and hICE groups. We observed significantly more adverse effects among patients treated with hICE. The BEAM regimen seems to be superior to hICE in terms of toxicity profile with comparable efficacy in patients with relapsed/refractory NHL and HL.

A feasible shortcut for the mobilization outcome: Steady state CD34 positive hematopoietic stem cells.

Predicting success of hematopoietic cell mobilization is an important issue for transplant physicians. We examined the steady state peripheral blood CD34+ cell count to predict ability to mobilize adequate hematopoietic progenitor cells in 63 myeloma and lymphoma patients. The median steady state CD34+ cell number was 1.56/µL (0.03-5.76). Although counting steady state CD34+ is definitely cost effective to predict the successful mobilization, we could not find a threshold steady state CD34 count of any value predicting successful mobilization.

Pandemic 2009 H1N1 influenza in patients with hematopoietic stem cell transplantation and hematologic malignancy: single center experience.

Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5-15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.