Autologous Stem Cell Transplantation in Multiple Myeloma Patients Over 60 Years Old

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and

Early Relapse After Autologous Stem Cell Transplantation in Multiple Myeloma is Still Prognostic in The Era of Novel Agents

Significant improvements in the prognosis of Multiple Myeloma(MM) have recently observed in the era of novel agents. Induction treatment, including new agents followed by conditioning regimen and upfront autologous stem cell transplantation(ASCT), has been accepted as the standard treatment approach for newly diagnosed eligible MM patients. Despite novel agents, upfront ASCT is still superior to conventional chemotherapy alone. Previous studies revealed that the duration between ASCT and relapse had predicted overall survival(OS), and meantime, it was widely used to determine the potential benefit from a second ASCT. However, the majority of the data collected reflects the treatment modalities before novel agents. In this study, we aimed to investigate the impact of post-transplantation early relapse(ER) on survival in the era of novel agents. The results of 155 MM patients that underwent ASCT at our center between January 2010 and May 2018 were analyzed retrospectively. The median follow-up duration was 20 months in the ER group, 27 months in the non-ER group, and 24 months in all patients. 33.3% of patients in the ER group and 71.4% of patients in the non-ER group were alive at the time of analysis. Median OS was 20.77±3.66 months in the ER group and 40.89±4.21 months in the non-ER group. We found a statistically significant relationship between the ER and the poor OS (p

Myelodysplastic syndrome is an acquired clonal hematopoietic stem cell.

TEZ10454Tez (Yandal Uzmanlık) -- Çukurova Üniversitesi, Adana, 2014.Kaynakça (s. 60-70) var.viii, 71 s. : res. (bzs. rnk.), tablo ; 29 cm.Amaç: Miyelodisplastik sendrom hematopoetik kök hücrelerinin etkilendiği klonal, edinsel bir hastalıktır. M genelde bir yaşlılık hastalığıdır. Medyan tanı yaşı 65-70’dir. Miyelodisplastik sendrom patofizyolojisinde pluripotent kök hücrelerinin neoplastik transformasyonu ile sonuçlanan bir dizi genetik değişikliğin rol oynadığı düşünülmektedir. Literatürde Miyelodisplastik sendrom ile ilgili çok sayıda mutasyon ve kromozomal aberasyon saptanmıştır. Miyelodisplazide tanı, çevresel kanda sitopeni kadar kemik iliğinde karakteristik dismorfik tablonun da tespitine bağlıdır. TET2 geni epigenetik programlamada önemli rolleri olan bir gen ailesinin üyesidir. TET-2 mutasyonları lenfoid veya miyeloid serinin tümörlerinde saptanmıştır. Bu tez çalışmasında kliniğimizdeki Miyelodisplastik sendrom olgularında TET-2 Mutasyon sıklığının saptanması ve bu mutasyonların prognostik göstergelerle korelasyonunun araştırılması amaçlanmıştır. Gereç ve Yöntem: Bu tez çalışması Çukurova Üniversitesi Tıp Fakültesi İç Hastalıkları Hematoloji Kliniği’nde yapılmıştır. İlk kez kliniğimizde tanı alan ve halen takip ve tedavileri kliniğimizce yapılan Miyelodisplastik sendromlu olgular çalışma için seçilmiştir. Kliniğimizde bu tanı ile takip edilmekte olan toplam 19 hasta saptanmıştır. KRAS geni kodon 12 ve 13 mutasyonları için PCR ve minisekanslama ve TET2 geni tüm ekzonlar ve CBL geni ekzon 8 ve ekzon 9 için PCR ve DNA dizi analizi yapılmıştır. Bulgular: Olguların hiçbirinde KRAS veya CBL Gen mutasyonu saptanmamıştır. Çalışma kapsamında incelenen 19 olgunun 14'ünde TET-2 geninde mutasyonu saptanmıştır. 4 olguda tek mutasyon ve 10 olguda birden fazla ekzonda mutasyon saptanmıştır. 19 olgunun 5'inde (% 26) protein yapı ve fonksiyonunu etkilemesi muhtemel TET-2 gen mutasyonu saptanmıştır. Sonuç: Miyelodisplastik sendrom olgularımızda TET-2 mutasyon oranı literatür ile uyumludur. Saptanan mutasyonların tamamı heterozigottur. Hasta sayımızın az olması nedeniyle bu çalışmada TET-2 ile Miyelodisplastik sendrom' da prognostik göstergeler arasında ilişki araştırılamamıştır. Ancak şüphesiz böyle bir ilişkinin varlığı ve yokluğu ile ilgili araştırmalara ihtiyaç vardır.Aim: Myelodysplastic syndrome is an acquired clonal hematopoietic stem cell disorder. Myelodysplastic syndrome is generally a disease of old age. The median age at diagnosis is 65-70. A number of genetic changes are believed to play a role in neoplastic transformation of pluripotent stem cells in Myelodysplastic syndrome. In the literature, a large number of mutations and chromosomal aberrations were identified to be associated with Myelodysplastic syndrome. The diagnosis of Myelodysplastic syndrome is based on dysmorphic bone marrow findings as well as peripheral blood cytopenias. TET2 is a member of a family of genes with important roles in epigenetic programming. TET- 2 mutations were previously detected in tumors of lymphoid or myeloid malignancies. In this study, we aimed to investigate the incidence rates of TET- 2 mutations in patients with Myelodysplastic syndrome and to determine whether presence of TET-2 mutation correlates with prognostic indicators. Material and Methods: The present thesis was conducted at hematology department of Çukurova Uuniversity Faculty of Medicine. Patients with Myelodysplastic syndrome whose initial diagnosis and follow-up were made were selected for the study. 19 patients with Myelodysplastic syndrome has been identified. PCR and mini-sequencing were performed for KRAS gene (codon12, 13) mutations and PCR and DNA lineage analysis were performed for TET 2 gene and CBL gene (exon 8,9). Results: TET-2 gene mutation was identified in 14 of 19 cases examined. Single mutation inTET-2 gene was identified in 4 cases and more than one mutation has been identified mutations in 10 cases. In 5 of 19 patients (26%) TET-2 gene mutations that are likely to affect protein structure and function have been identified. Conclusion: TET-2 mutation rate in our patients is consistent with the literature. Due to low sample size we were unable to investigate the relationship between prognostic marker in MYELODYSPLASTİC SYNDROME TET-2 mutations. However this issue certainly merits further studies

Comparison of one hour versus 90 minute postprandial glucose measurement in women with gestational diabetes; which one is more effective?

In the present study, we aimed to compare postprandial 90 minute measurements and postprandial 1 hour (PP1-HR) measurements for prediction of foetal growth disturbances and pregnancy complications. This was a prospective study conducted in Acıbadem Mehmet Ali Aydınlar University Altunizade Hospital in Department of Perinatology. The study group consisted of patients diagnosed with gestational diabetes. In each antepartum visit, the patients fasting plasma glucose as well as PP1-HR and 90 minute measurements were made. Perinatal and neonatal data were obtained from each patient. The rate of large for gestational age infants was increased in patients when either PP1-HR measurement above 140 mg/dl or postprandial 90 minute measurement above 165 mg/dl compared to patients with normal PP1-HR or postprandial 90 minute measurement. Preterm delivery rate was increased in patients with postprandial 90 minute measurement above 165 mg/dl but not in patients with PP1-HR measurement above 140 mg/dl. The optimal cut-off for postprandial 90 minute measurement was 165 mg/dl based on receiver operating characteristics curve. Our preliminary data show that postprandial 90 minute measurements are superior to PP1-HR measurements in predicting large for gestational age infants.Impact Statement What is already known on this subject? Gestational diabetes (GDM) is defined as any degree of glucose intolerance with onset or first recognition in pregnancy. Maternal hyperglycaemia has been linked to metabolic alterations in the foetus and thus brings about foetal macrosomia as well as other pregnancy complications such as preterm delivery and preeclampsia. What the results of this study add? The findings of the present study suggest that postprandial 90 minute predicted more cases of LGA infants than postprandial 1-hour (PP1-HR) measurements. In addition, the rate of preterm deliveries was found to be increased in patients with mean postprandial 90 minute measurements above 165 mg/dl compared to patients with postprandial 90 minute measurements below 165 mg/dl. However, the rate of preterm deliveries was similar in patients with elevated PP1-HR measurements and patients with normal PP1-HR measurements. What the implications are of these findings for clinical practice and/or further research? Our study is the first to investigate the usefulness of postprandial 90 minute in a prospective design. Our preliminary data show that postprandial 90 minute measurements are superior to PP 1 measurements in predicting LGA babies. It also correlates better with preterm deliveries

The effect of high-dose cytarabine followed by autologous hematopoietic stem cell transplantation on the outcome of patients with mantle cell lymphoma

Introduction: The aim of this study was to investigate the influence of high-dose cytosine arabinoside (HDAC)-containing treatments followed by autologous hematopoietic stem cell transplantation on the survival of patients with mantle cell lymphoma. Material and methods: The data of 27 MCL patients who were followed-up between January 2009 and December 2015 were analyzed retrospectively. Results: The median age of the patients was 63 (range, 45–82) with 22 (81.4%) males and 5 (18.6%) females. Eight of 27 patients were treated with HDAC-containing regimens either as induction or salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT). The patients who received HDAC-containing regimen followed by AHSCT were found to have better one-year survival compared to others (p = 0.03). Median follow-up of patient cohort was 27.6 months and median overall survival (OS) was not reached. The probability of one-year OS for all patients was 76.8%. Conclusion: Our findings suggest that HDAC treatment followed by AHSCT seems to provide the best outcome for young-fit patients presenting with mantle cell lymphoma

Nivolumab as a bridge to allogeneic hematopoietic stem cell transplantation is associated with improved survival

Objective: The aim of the present study was to compare the effects of nivolumab bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT) on progression-free survival (PFS) and overall survival (OS) and toxicity profile. Patients and Methods: The study population consisted of relapsed/refractory cases of HL, who were treated with nivolumab for disease control and subsequently underwent allo- SCT at our institution. The control group consisted of HL patients who relapsed or refractory after multiple lines of therapy and underwent allo-SCT without nivolumab before transplantation as bridging therapy. Results: The incidence of acute and chronic graft vs. host disease (GVHD) was similar in both groups. The 100-day mortality occurred in 1 patient (10%) in the nivolumab group and 4 patients (16.7%) in the control group (p = 0.54). During 30-month follow-up, PFS was achieved in 60% of patients in the nivolumab group and 45.8% in the control group (p = 0.69). OS during 30-month follow-up was 80% in the nivolumab group and 41.7% in the control group, OS was superior in patients in the nivolumab group than in the control group (p = 0.04). Conclusions: Allo-SCT after bridging therapy with nivolumab provides a survival advantage over patients who underwent allo-SCT without the bridging. Therapy with nivolumab in combination with post-transplant cyclophosphamide does not appear to increase GVHD

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Abstract Post-transplant cyclophosphamide has become a promising medical option after allogeneic HSCT. In this study we aimed to evaluate the efficacy of cyclophosphamide and cyclosporine combination in acute and chronic graft-versus-host disease (GvHD) prophylaxis in acute myeloid leukemia (AML) cases scheduled for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective analysis of data from 40 cases who underwent allogeneic HSCT under GvHD prophylaxis with cyclophosphamide and cyclosporine combination between April 2016 and August 2017 was made. Cyclophosphamide was given at daily doses of 50 mg/kg on post-transplant 3rd and 4th days, and cyclosporine was applied at daily doses of 3 mg/kg/day starting from the 5th post-transplant day. Cyclosporine dose was tapered beginning from the 45th postoperative day and completely discontinued on the 90th post-transplant day. Mean age was 38.25 ± 15.25 years. Posttransplant median follow-up was six months (6–17 months). Post-transplant, the number of deaths and mortality rates related and unrelated to transplantation were 5 (12.5%), and 2 (5%), respectively. Acute GvHD was diagnosed in 7 cases (17.5%), and relapse was noted in 9 cases (22.5%). Myeloablative or reduced intensity conditioning was performed in 22 (55%) and 18 (45%) patients, respectively. The distribution of the donors was as follows: match-related (n = 26; 65%), match-unrelated (n = 9, 22.5%) and haploidentical donors (n = 5; 12.5%). There was no statistically significant correlation between the transplant-related and unrelated mortality and parameters under investigation.Cyclophosphamide use appears to be a highly effective and promising strategy for acute GvHD prophylaxis in non-haploidentical allogeneic HSCT cases. Identification of the impact of cyclophosphamide use on the development of chronic GvHD needs further investigation

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