INTRODUCTION:Effective mobilization of Stem Cells(SCs) to peripheral blood (PB) is crucial for obtaining sufficient CD34+ cell numbers via apheresis. The ratio of pre-apheresis PB CD34+ cells is the best parameter for predicting the product CD34+ cell count. However, quantitating CD34+ PB cells requires flow cytometry, which usually takes two or more hours to obtain the results. We hypothesized that the product CD34+ cell count could be predicted using the counts of white blood cells (WBCs), mononuclear cells (MNCs), and pre-apheresis CD34+ cells. A formula that achieves this would substantially affect the efficiency and effectiveness of apheresis. We, therefore, aimed to estimate the number of CD34+ cells in the product using a formula that incorporates pre-apheresis PB WBC, MNC, and CD34+ cell counts and product WBC and MNC counts. METHODS:We examined the results of 373 leukapheresis procedures for SC mobilization. Effective separation of CD34+ PBSCs (count/μL) via apheresis was estimated using the following formula: [Product WBC (count/μL) × MNC (count/μL) × pre-apheresis CD34+ cell (percentage/μL)] ÷ [PB WBC count/μL × PB MNC (count/μL)]. RESULTS:A strong correlation was observed between the CD34+ cell count calculated using our formula and the post-apheresis CD34+ cell count measured via flow cytometry (R = 0.939, based on linear regression analysis). In the subgroup analysis, this correlation was observed for all the disease subgroups and healthy donors. CONCLUSION:We developed a formula that predicts the product CD34+ cell count and is useful for determining whether a second apheresis procedure will be required.

Background: The aim of this study was to evaluate whether cyclophosphamide administered after allogeneic stem cell transplantation (ASCT) from 9/10 HLA-Matched Unrelated Donors (MMUD) increases the rates of bloodstream infections (BSI) (fungal, viral (CMV, BK, hepatitis), bacterial), infectious complications (hemorrhagic cystitis(HC)) and infection-related mortality compared to allogeneic stem cell transplantation from matched related donors (MRD). Metods: This is a retrospective multicenter study. 45 MMUD ASCT patients who received posttransplant cyclophosphamide + methotrexate + calcineurin inhibitor compared with 45 MRD ASCT patients who received methotrexate + calcineurin inhibitor. Results: Although there was a statistically significant prolongation of neutrophil engraftment time in the PTCy arm, there was no statistically significant difference in bacterial BSI frequencies between the groups (PTCy; 9(20%), control;8 (17.8%), p=0.778). The distribution of CMV infection in the first 100 days was similar (p=0.827) but the distribution of CMV infection rate between the 100th and 365th days, was observed more frequently in the control group (p=0.005). HC rates and their grades were similar in both groups (PTCy; 4 (8.8%), control;6 (13.3%) p=0.502). The rates of VZV infection and invasive aspergillosis were similar in the PTCy and control groups (13.3% in the PTCy, and 17.8% in the control group p=0.561). IRM rate was statistically similar in both groups (13.3% in the PTCy arm and 17.8% in the control arm) Conclusions: The addition of PTCy to standard GvHD prophylaxis in MMUD ASCT does not lead to an increase in CMV reactivation, bacterial BSI, invasive fungal infection, viral hemorrhagic cystitis or infection-related mortality.

Background: Graft Versus Host Disease (GvHD), which can be observed at a rate of 30-80% after allogeneic stem cell transplantation (ASCT) is an important complication that adversely affects the survival and quality of the life of patients. Posttransplant cyclophosphamide (PTCy) effectively prevents GvHD after HLA-haploidentical ASCT. In our study, the use of PTCy in 1-antigen HLA-mismatched unrelated donor (9/10MMUD) ASCT was compared with standard GvHD prophylaxis in HLA-identical related donor (MRD) ASCT. Materials and Methods: We conducted a retrospective study of the comparison of 42 patients with 9/10 MMUD ASCT receiving PTCy+Methotrexate (MTX)+Calcineurin Inhibitor (CNI) and 37 patients with HLA-identical MRD who received MTX+CNI in 3 bone marrow transplantation centers. Results: Cumulative incidences of grade I-II (64.6% vs 45.4%, p=0.187) or grade III to IV acute GvHD (35.4% vs54.6%, p=0.187) and chronic GvHD (11.9% vs 29.7%, p=0.096) were similar in the PTCy group and control group. No statistically significant differences were observed between PTCy and the control group in overall survival rate (52.4% vs 62.2%, p=0.381), progression-free survival (1483.97 vs 1200.70 days, p=0.502), relapsed-related mortality rate (21.4% vs 16.2%, p=0.556) and treatment-related mortality rate (16.7% vs 21.6%, p=0.575). Conclusion: With the addition of PTCy to standard GvHD prophylaxis in 9/10MMUD ASCT, the risk of GvHD due to incompatibility and unrelated transplantation is eliminated, and transplantation success is achieved with MRD ASCT. PTCy-based prophylaxis is an effective and safe strategy to prevent GvHD in 9/10 MMUD ASCT without increasing the risk of relapse and treatment-related mortality.

Background: We aimed to estimate CD34(+) cells count in the yield and the average volume that should be collected with a Formula that includes leukocytes, mononuclear cells, and peripheral CD34(+) cells count before apheresis.Methods: A total of 373 leukapheresis procedures performed for stem cell mobilization by three apheresis centers, between 2011 and 2021 were reviewed retrospectively. CD34(+) cells, mononuclear cell, and leukocyte counts were performed from peripheral blood before the procedure. During the apheresis process, when yield reached 200 ml volume, the hemogram was performed again from the yield. The formula was used to estimate the total number of CD34(+) cells in the yield and the amount of yield to be collected.Results: A strong correlation was found between the CD34(+) cells count calculated with the Formula we used in the study and CD34(+) cells count measured by flow cytometry at the end of the procedure (R:0.939 according to linear regression analysis). In the subgroup analysis, this correlation was found in all disease subgroups and healthy donors as well.Conclusion: The volume required to be collected for the target CD34(+) cells per 'kg’ during the leukapheresis procedure can be easily calculated by pre-treatment CD34(+) cell, leukocyte, mononuclear cells count performed in the beginning and intermediate of the procedure. The Formula that we developed to predict the CD34(+) cells level also has been found to be useful in determining whether a second treatment day will be required, thus avoiding unnecessary prolongation of the procedure.

Context: There is still no clear information about the incidence and consequences of infections with cyclophosphamide (PTCy) administration as prophylaxis against graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives: Revealing the incidence of pre-vaccination bacterial and viral infections (cytomegalovirus [CMV], herpes virus, and BK-polyomavirus hemorrhagic-cystitis), infection-related mortality, and predictive factors associated with PTCy application after allo-HSCT was the study aim. Design: Patients who underwent allo-HSCT from 9/10–10/10 HLA tissue-matched, unrelated donors and received cyclophosphamide for post-transplant GVHD prophylaxis from 3 centers between 2015 and 2020 were retrospectively reviewed. Infections that developed in the first 100 days after transplantation were recorded. Patients: Forty-one patients, M/F: 25/16, were included in the study. The mean age was 40.8 years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, one biphenotypic leukemia, and 1 HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients. All patients received one myeloablative priming regimen [TBI (800–1200 cGy)+Flu (30 mg/m2×5), Cy (60 mg/kg×2) + TBI (1200 cGy), treosulfan (10 g/m2×3) + Flu (40 mg/m2×4)]. In GVHD prophylaxis, PTCy was administered 72 and 96 hours following transplantation in combination with calcineurin inhibitors ± methotrexate ± mycophenolate mofetil. Levofloxacin, valacyclovir, fluconazole, and trimethoprim-sulfamethoxazole were empirically given to all patients along with the transplant preparation regimen. Results: At least one episode of febrile neutropenia (FEN) developed in all patients during the transplantation process. More than one episode of FEN developed in 22% of the patients. One patient died due to septic shock on post-transplant day 9. The incidence of CMV infection requiring treatment was 36.6% in the first 100 days and 41.5% at 1 year. All patients except 1 were CMV IgG-positive before transplantation. CMV reactivation was observed in 50% (15/15) of donor/patient CMV IgG (+/+). CMV reactivation was found in 30% (3/7) of the donor/patient CMVIgG (–/+) patients. Only one of these patients received antiviral therapy due to multiple reactivations. In 4 patients, CMV pneumonia developed, and 3 of them died. The rate of polyomavirus-associated cystitis was 7.3% (3/41). In the first year after transplantation, invasive fungal infection occurred in only 4 patients (9.8%), herpes virus infection occurred in 1 patient. Three patients received tenofovir–entecavir treatment because of anti-HBcIg positivity, and HBV reactivation was not detected in any of the patients. Conclusion: GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor does not have an increased risk in terms of bacterial, viral, or fungal infections and can be used safely. There is still no clear information about the incidence and consequences of infections with cyclophosphamide (PTCy) administration as prophylaxis against graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Revealing the incidence of pre-vaccination bacterial and viral infections (cytomegalovirus [CMV], herpes virus, and BK-polyomavirus hemorrhagic-cystitis), infection-related mortality, and predictive factors associated with PTCy application after allo-HSCT was the study aim. Patients who underwent allo-HSCT from 9/10–10/10 HLA tissue-matched, unrelated donors and received cyclophosphamide for post-transplant GVHD prophylaxis from 3 centers between 2015 and 2020 were retrospectively reviewed. Infections that developed in the first 100 days after transplantation were recorded. Forty-one patients, M/F: 25/16, were included in the study. The mean age was 40.8 years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, one biphenotypic leukemia, and 1 HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients. All patients received one myeloablative priming regimen [TBI (800–1200 cGy)+Flu (30 mg/m2×5), Cy (60 mg/kg×2) + TBI (1200 cGy), treosulfan (10 g/m2×3) + Flu (40 mg/m2×4)]. In GVHD prophylaxis, PTCy was administered 72 and 96 hours following transplantation in combination with calcineurin inhibitors ± methotrexate ± mycophenolate mofetil. Levofloxacin, valacyclovir, fluconazole, and trimethoprim-sulfamethoxazole were empirically given to all patients along with the transplant preparation regimen. At least one episode of febrile neutropenia (FEN) developed in all patients during the transplantation process. More than one episode of FEN developed in 22% of the patients. One patient died due to septic shock on post-transplant day 9. The incidence of CMV infection requiring treatment was 36.6% in the first 100 days and 41.5% at 1 year. All patients except 1 were CMV IgG-positive before transplantation. CMV reactivation was observed in 50% (15/15) of donor/patient CMV IgG (+/+). CMV reactivation was found in 30% (3/7) of the donor/patient CMVIgG (–/+) patients. Only one of these patients received antiviral therapy due to multiple reactivations. In 4 patients, CMV pneumonia developed, and 3 of them died. The rate of polyomavirus-associated cystitis was 7.3% (3/41). In the first year after transplantation, invasive fungal infection occurred in only 4 patients (9.8%), herpes virus infection occurred in 1 patient. Three patients received tenofovir–entecavir treatment because of anti-HBcIg positivity, and HBV reactivation was not detected in any of the patients. GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor does not have an increased risk in terms of bacterial, viral, or fungal infections and can be used safely.

Context: The ideal prophylaxis regimen for graft versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor has not yet determined clearly. Comparative studies on anti-thymocyte globulin (ATG), calcineurin inhibitors, methotrexate, mycophenolatmofetil (MMF), post-transplant cyclophosphamide (PTCy), and their combinations are very limited. Objectives: Although ATG and its combinations have been used frequently in the past, PTCy use has been increasing due to positive developments in recent years. Evaluating the effect of cyclophosphamide-based GVHD prophylaxis after 9/10 and 10/10 HLA tissue-matched unrelated stem cell transplantation was aimed. Design: Patients who underwent allo-HSCT from a 9/10-10/10 HLA tissue-matched unrelated donor and used cyclophosphamide+tacrolimus+methotrexate or cyclophosphamide+cyclosporine for post-transplant GVHD prophylaxis in 3 centers between 2015 and 2020 were reviewed retrospectively. Forty-one patients (25 male and 16 female) were included in the study. The mean age of the patients was 40.8 years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, 1 biphenotypic leukemia, and 1 HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients. As a myeloablative regimen, 35 patients had TBI (800–1200 cGy)+Flu (30 mg/m2x5), 5 had Cy (60 mg/kgx2)+TBI (1200 cGy),1 had treosulfan (10 gr/m2x3)+Flu (40 mg)/m2x4). In 27 patients, tacrolimus (from the 3rd day)+MTX (+1,+3,+6th day) with PTCy (at hours 72 and 96 after transplantation), in 13 patients cyclosporine (from day +3) with PTCy (at at hours 72 and 96), in 1 patient cyclosporine (from +5th day)+mycophenolate mofetil (from +5th day) together with PTCy (at hours 72 and 96) was given. Results: Mean neutrophil engraftment was on the 18th day (11–31), and mean thrombocyte engraftment was on the 22nd day (9–48). Acute GVHD was observed (Grade I–II) in 26.8% of patients, Grade III–IV in 4.9%, and chronic GVHD in 12.2%. Post-transplant mortality rates were day 30: 4.9%, day 100: 2.2%, day 180: 25.7%, and the first year: 34.3%. Transplant-related mortality was 2.4%, relapse-related mortality was 21.9%, and non-relapse-related mortality was 31.7%. Comparison of our cases with the literature of unrelated allo-HSCT cases treated with ATG were as follows: acute GVHD Grade I–II (26.8% vs 45%), Grade III–IV (4.9 vs 27%), chronic GVHD (12.2% vs 65%), respectively. Recurrence-related and non-relapse-related mortality rates were significantly lower from most literature, and 1-year survival rates are higher than cases with ATG. Conclusion: GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor is thought to be more effective and safe than ATG. The ideal prophylaxis regimen for graft versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor has not yet determined clearly. Comparative studies on anti-thymocyte globulin (ATG), calcineurin inhibitors, methotrexate, mycophenolatmofetil (MMF), post-transplant cyclophosphamide (PTCy), and their combinations are very limited. Although ATG and its combinations have been used frequently in the past, PTCy use has been increasing due to positive developments in recent years. Evaluating the effect of cyclophosphamide-based GVHD prophylaxis after 9/10 and 10/10 HLA tissue-matched unrelated stem cell transplantation was aimed. Patients who underwent allo-HSCT from a 9/10-10/10 HLA tissue-matched unrelated donor and used cyclophosphamide+tacrolimus+methotrexate or cyclophosphamide+cyclosporine for post-transplant GVHD prophylaxis in 3 centers between 2015 and 2020 were reviewed retrospectively. Forty-one patients (25 male and 16 female) were included in the study. The mean age of the patients was 40.8 years (21–67), with 23 AML, 11 ALL, 3 NHL, 2 MDS, 1 biphenotypic leukemia, and 1 HL diagnosis. HLA tissue compatibility was 9/10 in 32 patients and 10/10 in 9 patients. As a myeloablative regimen, 35 patients had TBI (800–1200 cGy)+Flu (30 mg/m2x5), 5 had Cy (60 mg/kgx2)+TBI (1200 cGy),1 had treosulfan (10 gr/m2x3)+Flu (40 mg)/m2x4). In 27 patients, tacrolimus (from the 3rd day)+MTX (+1,+3,+6th day) with PTCy (at hours 72 and 96 after transplantation), in 13 patients cyclosporine (from day +3) with PTCy (at at hours 72 and 96), in 1 patient cyclosporine (from +5th day)+mycophenolate mofetil (from +5th day) together with PTCy (at hours 72 and 96) was given. Mean neutrophil engraftment was on the 18th day (11–31), and mean thrombocyte engraftment was on the 22nd day (9–48). Acute GVHD was observed (Grade I–II) in 26.8% of patients, Grade III–IV in 4.9%, and chronic GVHD in 12.2%. Post-transplant mortality rates were day 30: 4.9%, day 100: 2.2%, day 180: 25.7%, and the first year: 34.3%. Transplant-related mortality was 2.4%, relapse-related mortality was 21.9%, and non-relapse-related mortality was 31.7%. Comparison of our cases with the literature of unrelated allo-HSCT cases treated with ATG were as follows: acute GVHD Grade I–II (26.8% vs 45%), Grade III–IV (4.9 vs 27%), chronic GVHD (12.2% vs 65%), respectively. Recurrence-related and non-relapse-related mortality rates were significantly lower from most literature, and 1-year survival rates are higher than cases with ATG. GVHD prophylaxis containing PTCy after allo-HSCT from an unrelated donor is thought to be more effective and safe than ATG.

Objectives: Tyrosine kinase inhibitor (TKI) resistance is one of the major obstacles in chronic myeloid leukemia (CML) treatment.Ceramide, the central molecule of the sphingolipid metabolism, is synthesized by ceramide synthases (CERS1-6).While ceramide is known to be a pro-apoptotic molecule, glucosylceramide and sphingosine 1-phosphate converted from the ceramide are anti-apoptotic.In this study, we aimed to determine the potential roles of bioactive sphingolipids in terms of predicting drug resistance and prognosis in chronic myeloid leukemia patient samples.Materials and methods: Expression levels of CERS1-6, GCS, SK1, and BCR/ABL genes of 66 CML patients that are newly diagnosed, TKI-resistant or TKI-sensitive were analyzed by qRT-PCR.Results: CERS1-6 genes were expressed higher in the patients treated with TKIs than that of the patients newly diagnosed and TKI-resistant.However, expression levels of anti-apoptotic GCS and SK1 genes were significantly higher in TKI-resistant and blastic phase patients than that of other patients.Additionally, BCR/ABL expression levels were higher in newly diagnosed and TKI-resistant patients.Conclusion: Our results suggest that expression levels of bioactive sphingolipid genes might be novel markers for determination of drug resistance in CML patients.More importantly, they might be used as novel targets for more effective treatment of resistant CML patients.

Introduction Despite major improvements in allogeneic hematopoetic stem cell transplantation 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. Ibrutinib is a first class inhibitor of BTK was recently employed in corticosteroid-refractory chronic GVHD with encouraging overall response rates. Herein, we share a real-life experience using ibrutinib in the treatment of steroid-refractory cGVHD. Patients and Methods This multicenter retrospective study conducted in 10 different stem cell transplant centers included 44 adult patients diagnosed with steroid-refractory cGVHD. We treated off-label these patients from June 2017 to July 2019 with ibrutinib with a dose of 420 mg. Organ sites affected and cGVHD grading were classified according to the NIH 2014 criteria. Results 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 67 % of patients showed evidence of cGVHD in more than two organs. The median Karnofsky Performance Status score was 65%. At a median follow-up of 22.3 months (range 7.1-109 months) after evidence of cGVHD showed, 36 (81.8%) patients were still receiving ibrutinib and 4 (9.1%) had discontinued treatment, because of cGVHD progression. Treatment duration ranged from 2 to 12 months (median 6 months) for all patients. Only three patients had grade 2 muscle spasm, arrhythmia and diarrhea as adverse events and need to reduce the 25% of drug dosage. No several adverse events due to ibrutinib were observed in our cohort. In the all treated population, based on the 2005 NIH cGVHD Consensus Panel response criteria, 45.5% PR and 20.5% CR were achieved. Six patients had progression on manifestations of cGVHD. For the responders, the median time to initial response was 28 days. Nine patients had stable disease under the ibrutinib treatment and still continue receiving. Analysis by organ domain showed similar rates of response in the lung (76.4%) skin (66.7%), and GIS (57.1%). However the response in the liver (54.2%) was lower than the others. Out of 17 patients with bronchiolitis obliterans as a manifestation of cGVHD, we observed an immediate improvement in stability of FEV1 decline that persisted over the study period despite the decreased steroid dosing in 13 patients, 3 patients had stable FEV1 and only 1 patient had reduction in FEV1. Discussion Our study suggests that ibrutinib is a safe and effective agent that reduces steroid requirements and stabilizes lung function in patients with bronchiolitis obliterans as a manifestation of cGVHD. Our study adds to a growing body of evidence for ibrutinib's use in cGVHD. It is important to note that, larger prospective studies are needed to verify and augment our findings.

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).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Introduction: Pomalidomide is a potent immunomodulatory drug (imid) with efficacy demonstrated in relapsed refractory multiple myeloma. In a phase 3 study, pomalidomide showed a benefit of PFS and OS over high dose dexamethasone, even in proteasome inhibitor and imid refractory patients. In our country, Pomalidomide has recently gained approval in relapsed refractory setting in patients who were both refractory to a proteasome inhibitor and an immunomodulatory drug. Before this approval we were able to use pomalidomide as a single agent or as part of a combination approach via approval of health authority. Here we present our retrospective, multicenter, real life experience among patients with relapsed refractory myeloma and treated with pomalidomide. Methods: 117 heavily pre-treated patients from 12 centers were retrospectively evaluated and the data among the use of pomalidomide, its efficacy and safety were analyzed. Results: Median age of the patients included in the study was 68 (32-85) with a male ratio of 52.1%. ISS groups at diagnosis were as follows, stage 1 20.5%, stage 2 47% and stage 3 32.5%. 13 of 45 patients (28.9% ) were classified as high risk myeloma with an either del 17p or t(4,14) FISH positivity. Most of the patients were refractory to at least one proteasome inhibitor (96.6%), at least one imid (94%), or both (92.3%), even 27.4% were refractory to carfilzomib. Great majority (91.5%) of patients received pomalidomide as a single agent with concomitant corticosteroids. All patients included in the study were able to receive at least 2 cycles of pomalidomide. Median number of prior therapy line was 5 (2-11). Overall response rate, complete response + very good partial remission rate and partial remission rates were 35%, 11% and 24% respectively. Median duration of response was 4 months. Median progression free survival was 5.6 months and median overall survival was 8.4 months after initiation of pomalidomide. Overall survival was 4 months in patients who were not able to achieve at least stable disease. Hematological toxicity was the major toxicity which were reported at 77% of patients. Other major toxicities were as follows: fatigue 27.3%, pneumonia 20.5%, sepsis 12% (either neutropenic or non-neutropenic) and renal toxicity 6%. Conclusions: Pomalidomide is an efficient option in advanced multiple myeloma. Even in a heavily pre-treated real-life patient group pomalidomide led to a significant overall response rate. Pomalidomide was well tolerated with manageable adverse events in this heavily pre-treated patient cohort. Most important side effects were hematologic and infectious. Proper infectious prophylaxis may decrease the rates of adverse events. Overall survival was relatively short after pomalidomide failure. Combination approaches with other novel agents may increase the response rates and prolong survival in such advanced relapsed/refractory patients. Disclosures No relevant conflicts of interest to declare.

Background and Aim: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are one of the sources of adult stem cells being explored for potential use in repairing neurodegenerative disorders. In this study, it was aimed to investigate the useful effects of BM-MSCs therapy on the streptozotocin-induced neurodegeneration in rats. Materials and Methods: Adult female Wistar rats were bilaterally injected intra-cerebroventricularly with streptozotocin (3 mg/kg) for neurodegeneration. Water maze tests were used to monitor spatial learning and memory. One or two intravenous injections of BM-MSCs were administrated to rat via the tail veins. At the end of the study, all rats were sacrificed for histological evaluation and immunohistochemistry. Results: Streptozotocin group demonstrated a significant increase in escape latency in comparison with both control groups (Sham and Saline), whereas rats treated with BM-MSCs exhibited a decrease in escape latency in comparison with streptozotocin group. The percentage of time spent in the target quadrant and the mean number of platform crossings did not change in all the groups. BM-MSCs administration improved spatial learning but not memory. However, improvement in neuronal cells in hippocampal CA1 region was only observed in the rats treated with BM-MSCs twice as opposed to the rats treated with BM-MSCs once or with saline. Conclusions: In this study, mesenchymal stem cells therapy failed to improve the streptozotocin-induced neurodegeneration like Alzheimer’s disease in rats.

Thesis (Master)--Izmir Institute of Technology, Molecular Biology and Genetics, Izmir, 2014

PPARs are ligand-regulated transcription factors and regulate expression of several gene products. Therefore, PPARs are being studied for their possible contribution to the treatment of cancer, atherosclerosis, inflammation, infertility and demyelinating diseases. Primary AML patients were observed to have significantly elevated PPARγ mRNA expression compared to normal peripheral blood or bone marrow mononuclear cells. This study investigated the cytotoxic effects of rosiglitazone maleate, a pure PPARγ agonist, in vitro in HL-60 cell line. This study obtained results which can provide guidance for future studies. Whether the PPARy agonist rosiglitazone maleate may provide additive effects in refractory or relapsing cases of acute leukemia may be set as an objective for the future studies.

BACKGROUND/AIMS:Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. MATERIALS AND METHODS:Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×106 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. RESULTS:No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with non-responder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. CONCLUSION:Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.