Meltem Ayli - Academia.edu (original) (raw)

Papers by Meltem Ayli

Leukemia research, May 1, 2024

Turkiye Klinikleri Nuclear Medicine - Special Topics, 2021

Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2021

Context The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab ... more Context The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Objective To determine the impact and safety of BV as maintenance after ASCT in real-world patients. Design Patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were retrospectively analyzed. Setting All patients were followed by the bone marrow transplantation team of their hospital. Patients or Other Participants Seventy-five patients were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease Interventions BV consolidation was initiated within 6 months of ASCT and administered at a dose of 1.8 mg/kg intravenous infusion over 30 min every 3 weeks for up to 16 cycles in an outpatient setting. Main Outcome Features The primary endpoint of the study was PFS; secondary endpoints were safety and overall survival (OS). Results At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in six, and SD in three patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-years PFS and OS rates were 67.75% (95% CI:0.55–0.77) and 87.61% (95% CI:0.76–0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV naive and BV exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to AE in 12 patients. Conclusions Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55–0.75) with an acceptable toxicity profile.

Leukemia Research, Oct 1, 2019

Marginal zone lymphoma accounts 5%-17% of all non-Hodgkin lymphomas and has an indolent clinical ... more Marginal zone lymphoma accounts 5%-17% of all non-Hodgkin lymphomas and has an indolent clinical course. The parameters that predict prognosis and the need for treatment are still unclear. The aim of the current study was to examine the impact of parameters on the course of disease and the need for treatment in marginal zone lymphoma. Methods A retrospective study was conducted with marginal zone lymphoma patients in the two centres between 2010 and 2018. The demographic and disease characteristics, and also hematological and biochemical parameters at the time of diagnosis were examined. The effect of the parameters on overall survival and need for treatment were analyzed. Results During the follow-up, 25 patients required treatment and 15 patiens were followed up without treatment. Overall survival was signi cantly higher in patients with nodal marginal zone lymphoma than in extranodal and splenic marginal zone lymphoma patients. overall survival of patients who required treatment was 92.9 months while untreated patients was 58.4 months and there was no signi cant difference among the groups. The platelet count of untreated patients at the time of diagnosis were signi cantly higher than patients who received treatment. No signi cant relationship was found between any parameter and overall survival. Conclusions We demonstrated platelet count at the time of diagnosis as a predictive factor for future treatment need. It is an objective and simple blood test that may be helpful to predict the course of the disease although further studies are warranted.

$Research paper thumbnail of Conditioning Regimens for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Stem Cell Transplantation: BEAM Versus High Dose ICE$

Indian Journal of Hematology and Blood Transfusion, Jul 8, 2020

There are different drug combinations and conditioning regimens in lymphoma transplants. However,... more There are different drug combinations and conditioning regimens in lymphoma transplants. However, no randomized data is available to demonstrate the superiority of any regimen and the optimal choice is unknown. In this analysis, we compared the efficacy, toxicity and the survival outcomes of the BEAM and the high dose ICE (hdICE) conditioning regimens in relapsed NHL and relapsed/refractory Hodgkin Lymphoma patients undergoing auto-SCT. 83 patients with relapsed/refractory HL or relapsed NHL who were treated with Auto-SCT between 2006 and 2016, were analyzed retrospectively. 52 patients (62.7%) received BEAM, while 31 patients (37.3%) received hdICE. Between two groups there is no significant difference in age, gender, diagnosis, disease stage, chemosensitivity, ECOG performance status, time from diagnosis to transplant, salvage regimens and previous lines of chemotherapy. After a median of 59-month follow-up, PFS and OS rates of both groups were similar (5-year PFS was 51.6% in BEAM group, 48.8% in hdICE group, p = 0.71; 5-year OS was 58% in BEAM group, 54.8% in hdICE group, p = 0.93). The median neutrophil (11 vs. 10 days, p = 0.06) and platelet engraftment (13 vs. 11 days, p = 0.01) was faster and demand of transfusions were lesser in hdICE group (p = 0.03). However, severe renal toxicity was significantly higher in hdICE group in our study (p = 0.01). hdICE conditioning regimen may be used as an alternative to BEAM, with similar survival outcomes and toxicity profile, especially transplant centers that experience some difficulties in the availability of the carmustine.

Bone Marrow Transplantation, Sep 6, 2004

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thi... more The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m 2), melphalan (100 mg/m 2), and carboplatin (1050-1350 mg/m 2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a totalbody irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occured in five of 42 (12%) patients and death due to grade-4 RRT occured in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.

Turkiye Klinikleri Tip Bilimleri Dergisi, 2008

Medeniyet medical journal, Mar 27, 2023

Objective: Standard-dose methylprednisolone (methyl-Pd) is generally preferred as the first-line ... more Objective: Standard-dose methylprednisolone (methyl-Pd) is generally preferred as the first-line treatment in immune thrombocytopenia (ITP) unless there is an urgent indication to increase the platelet value. A significant proportion of patients (around 40%) does not benefit from this treatment. This study investigated whether pretreatment platelet level and other hemogram indices in patients with ITP patients can be used to predict early response to standard-dose methyl-Pd treatment. Methods: Patients who received first-line standard-dose methyl-Pd therapy with the diagnosis of primary ITP were included. Patients were categorized as complete responder (CR), responder (R), and nonresponder (NR) according to the response status obtained within the first 14 days of treatment. The hemogram indices of the CR, R, and NR groups measured at the start of the treatment were compared retrospectively. Results: One hundred forty four patients with ITP were included in the study. The number of patients with NR, R, and CR were 47 (33%), 40 (28%), and 57 (39%), respectively. The mean platelet level of the NR group was lower than responders (R and CR groups) (p=0.002 and p=0.049, respectively). The mean platelet volume (MPV) levels of the NR group were statistically lower than that of the CR group (p=0.018). If MPV ≥10 fL and platelet >12,000/mm³, the probability of an early response with methyl-Pd is higher [sensitivity =98.1% (95% confidence interval (CI) =89.7-99.9%), specificity =45% (95% CI =23.1-68.5%), positive predictive value =82.3% (95% CI =75.7-87.4%), negative predictive value =90% (95% CI =54.9-98.5%)].

Bone Marrow Transplantation, May 1, 2003

This study was conducted to evaluate the efficacy of highdose thiotepa, melphalan and carboplatin... more This study was conducted to evaluate the efficacy of highdose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m 2), melphalan (100 mg/m 2) and carboplatin (1200-1350 mg/m 2). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n ¼ 2) or early death due to transplant-related complications (n ¼ 3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%), 10 are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n ¼ 17) and responsive (n ¼ 10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR* following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR* following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.

Blood, Nov 29, 2018

Introduction:Despite major improvements in allogeneic hematopoetic stem cell transplantation (All... more Introduction:Despite major improvements in allogeneic hematopoetic stem cell transplantation (Allo-SCT) form matched related/unrelated donor over last decades, chronic graft-versus-host disease (cGVHD) is still the leading cause of late treatment-related deaths among recipients (Lee et all, Blood2002). Novel insights into the pathophysiology of GVHD highlighted the relevant role of the host inflammatory response governed by Bruton tyrosine kinase (BTK) signaling pathway. Ibrutinib is a first class, once daily inhibitor of BTK with proven efficacy in B cell lympho-proliferative diseases, was recently employed in corticosteroid- refractory chronic GVHD with encouraging overall response rates(Miklos et all, Blood 2017). Patients and Methods:This real-life, multicenter retrospective study conducted in 6 centers from Turkey included 14 adult patients diagnosed with steroid-refractory cGVHD. All patients were transplanted using grafts from HLA-matched peripheral blood stem cell source. We treated off-label these patients from June 2017 to July 2018 with ibrutinib with a dose of 420 mg P.O. qday. Organ sites affected and cGVHD grading before starting ibrutinib were classified according to the National Institues of Health (NIH) 2014 criteria. Steroid refractory cGVHD was defined as any disease that failed to respond to previous immunosuppressive therapy with steroids at least 4 weeks or inability to taper it with or without additional immunosuppressive drugs. Results:The baseline characteristics of the patients are listed in Table 1. Patients had undergone both myeloablative and non-myeloablative Allo-SCT for a variety of underlying hematological malignancies. As expected mouth and skin were the most frequently involved organs and 79% of patients showed evidence of cGVHD in more than 2 organs. The median Karnofsky Performance Status score was 75% (30%-100%). At a median follow-up of 26.7 months (range, 3.2-70.9 months) after evidence of cGVHD showed, 12 (85.7%) patients were still receiving ibrutinib and 2 (14.3%) had discontinued treatment, because of cGVHD progression. Treatment duration ranged from 2 to 12 months (median 6 months) for all patients. Only one patient had grade 2 muscle spasms as adverse event and need to reduce the 25% of drug dosage. No several adverse events due to ibrutinib was observed in our cohort. In the all treated population, the overall response rate (ORR), based on the 2005 NIH cGVHD Consensus Panel response criteria, was 71.4%, with a CR rate of 28.6 % and a PR rate of 42.9 %. For the responders, the median time to initial response was 28 days. Two patients had stable disease under the ibrutinib treatment and still continue receiving. Analysis by organ domain showed similar rates of response in the skin (91.7%), lung (85.7%) and mouth (80%). However the response in the liver (71.4%) was lower than the others. At the time of data collection, no patient has deceased. Discussion:In the absence of an approval treatment of steroid-refractory cGVHD, there is currently no consensus on the optimal second-line treatment. Treatment choices are based on mostly physician experience, ease of use and risk of toxicity. Based on the results of our limited study; the clinically meaningful response with safety profile observed with ibrutinib as a salvage therapy for chronic GVHD in accordance with Miklos and colleagues&amp;amp;amp;amp;#39;s report. However, in contrast to their results; patients with skin and lung manifestations of cGVHD were appeared to have somewhat better responses to ibrutinib than patients with cGVHD involving liver. It is important to note that prospective randomized controlled studies with large number of patients are warranted to find out the standard regimen for steroid-refractory cGVHD. Disclosures Ilhan: Alexion: Speakers Bureau; Roche: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau. Civriz Bozdag:TAKEDA: Consultancy; MSD: Research Funding; NOVARTIS: Consultancy. Özcan:Takeda: Honoraria, Other: Travel payment, Research Funding; Novartis: Research Funding; Roche: Honoraria, Research Funding; Abbvie: Other: Travel payment; Jazz: Other; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Bayer: Research Funding; MSD: Research Funding; Celgene: Other: Travel support, Research Funding; Archigen: Research Funding; MSD: Other: travel support, Research Funding; Jazz: Other: Travel support.

Clinical Laboratory, 2016

In this study, we aimed to determine a cutoff level for CD38 that would aid us in identifying chr... more In this study, we aimed to determine a cutoff level for CD38 that would aid us in identifying chronic lymphocytic leukemia patients in need of early therapy and predicting patients at sufficiently low risk who would likely exhibit a rapid improvement; we also aimed to find out if CD38 expression would show variability during disease course and determine the extent of CD38 expression. 124 patients were diagnosed with CLL. CD38 and ZAP-70 expression levels were measured with four color flowcytometry. Time from diagnosis to initial therapy was calculated for all patients. CD38 expression was studied for a second time during follow-up in 50 patients. For cutoff levels of 7%, 20%, and 30%, CD38 expressions were 61.3%, 25%, and 24.2%, respectively. At all three cutoff levels there were significant correlations with all parameters except age between CD38+ vs. CD38- groups (p &amp;amp;amp;lt; 0.001). The comparative rates of starting therapy for cutoff levels of 7%, 20%, and 30% in CD38+ and CD38- groups were 77.5% vs. 6.25%; 100% vs. 30.7%, and 100% vs. 31.5%, respectively (p &amp;amp;amp;lt; 0.001). Multiple Cox Proportional Hazards Regression analysis: for a cutoff level of 7%, survival was affected by STAGE, ZAP70, and CD38. A CD38 cutoff level of 7% determined by standardized laboratory techniques is an important prognostic marker. However, the number and frequency of repeat measurements of CD38 expression, and cutoff level of CD38 expression that significantly predict disease prognosis should be further determined by future cohort studies.

Nephron, 2000

Hypoproteic diets are most often discussed for patients with chronic kidney disease (CKD) who do ... more Hypoproteic diets are most often discussed for patients with chronic kidney disease (CKD) who do not receive dialysis. A very low-protein diet supplemented with ketoanalogues of essential amino acids (keto-diet) proved effective in ameliorating metabolic disturbances of advanced CKD and delaying the initiation of dialysis without deleterious effects on nutritional status. Several recent studies report that the keto-diet could also slow down the rate of decline in renal function, with better outcomes after the initiation of dialysis. Results of a single-center randomized controlled trial addressing the rate of CKD progression revealed a 57% slower decline in renal function with the keto-diet compared with a conventional low-protein diet (LPD). The keto-diet allowed the safe management of selected patients with stage 4-5 CKD, delaying dialysis for almost 1 year, with a major impact on patient quality of life and health expenditures. Therefore, the keto-diet could be a link in the integrated care model. Careful selection of patients, nutritional monitoring, and dietary counseling are required.

Bone Marrow Transplantation, Jun 1, 2002

l leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage ... more l leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage of adding 60 min to the time the patient was on the machine.

Leukemia Research, May 1, 2023

Blood, Dec 6, 2014

Introduction&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Introduction&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;Aim:Chronic myeloid leukemia (CML) is a hematopoietic pluripotent stem cell disease where myeloid cells lead to uncontrolled proliferation. Current treatment of Ph (+) CML is based on the inhibition of tyrosine kinase inhibitors (TKI), especially second generation drugs. Majority of CML patients are male and 46% of them are between 20 and 64 years of age. Therefore, it is conceivable that inhibition of c-kit or PDGFR by TKI may have deleterious effects on spermatogenesis or folliculogenesis, resulting in male or female subfertility. Aim of this study is to determine the effect of nilotinib on spermatogenesis and folliculogenesis which is used routinely to treat CML. Materyal&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;Method: Here we present the results of testicular and ovarian changes after nilotinib administration to five-week old male and female C57bI6 mice. Mice received 0.4 mg of nilotinib per day dissolved in the drinking water for 2 months. Control group received only drinking water. Treatment dose was determined according to the clinical studies regarding the plasma concentrations (20 mg/kg, orally). After sacrification of both groups, testicular and ovarian tissues were fixed and parafin sections were stained with hematoxylene-eosin. In the ovaries, the follicles were counted and their developmental stages were recorded from the serial sections. In the testes, 24 seminiferous tubules with approximately circular cross-sectional profiles were assessed using a classification according to the degree of spermatogenic activity to generate a mean score for each mouse. In addition, tubule diameters were measured using an eyepiece micrometer to provide an additional indication of the level of function. Results:There was less distance between the cortex and medulla than normal, and the follicles were widely scattered instead of organized in a normal hierarchy from the least mature at the periphery to the largest growing stages towards the medulla. The numbers of follicles were significantly different between nilotinib and control groups (268±110 vs. 170±60; p= 0.03). Virtually every seminiferous tubule from all animals had active spermatogenesis with either spermatids or spermatozoa present. Mean tubular diameter measurements were 190,61±8,33 vs. 194,32±7,26 in control and nilotinib groups, respectively (p=0.475). Spermatogenic activity index were not significantly different between control and nilotinib groups (3.1 vs. 3.4; p=0.241). Conclusion: Unlike the manufacturer’s results; we showed the supression of folliculogenesis and prevention of spermatogenesis during the long-term nilotinib treatment. Our results indicate that nilotinib, within the dose of CML treatment regimen, may create gonadotoxicity and therefore its usage may be an indication for fertility preservation. In the second part of our ongoing study, we are investigating the effect of nilotinib on fertility and teratogenicity. Disclosures No relevant conflicts of interest to declare.

Transfusion and Apheresis Science, Sep 1, 2012

Turkiye Klinikleri Hematology - Special Topics, 2016

Türk biyokimya dergisi, 2014

Kan kaybına bağlı hemoglobin düşüklüğü ve hipoksemi durumunda kardiak iskemi belirteci olarak İMA... more Kan kaybına bağlı hemoglobin düşüklüğü ve hipoksemi durumunda kardiak iskemi belirteci olarak İMA [The evaluation of IMA as a cardiac ischemia marker in the cases of hypohemoglobinemia and hypoxemia due to blood loss]