Germline pathogenic variant spectrum in 25 cancer susceptibility genes in Turkish breast and colorectal cancer patients and elderly controls.

Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer-free elderly controls, using next-generation sequencing-based multigene panel testing and multiplex ligation-dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high-risk BC patients and 26.4% of high-risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two-thirds of all pathogenic variants detected in high-risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high-risk BC patients (4.5%). BRCA1 exons 17-18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC, and they are likely to be founder variants. Three frequent MUTYH pathogenic variants (c.884C>T, c.1437_1439delGGA and c.1187G>A) were responsible for all MUTYH biallelic cases (4.4% of high-risk CRC patients). The total pathogenic variant frequency was very low in controls (2.4%) and in low-risk BC (3.9%) and CRC (6.1%) patients. Our study depicts the pathogenic variant spectrum and prevalence in Turkish BC and CRC patients, guiding clinicians and health authorities for genetic testing applications and variant classification in Turkish population.

Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes.

INTRODUCTION: Allogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors' age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. METHOD: Sixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009-2019 were enrolled for the study. All donors received 4-5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50-54 group A, 55-59 group B, aged 60 and older group C. RESULTS: Pre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). CONCLUSION: Adequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.

The same mutation in a family with adenosine deaminase 2 deficiency.

The deficiency of adenosine deaminase 2 (DADA2) has recently been defined as a monogenetic autosomal recessive autoinflammatory disease. DADA2 is mainly characterized by high fever, livedo racemose, early-onset stroke, mild immunodeficiency and clinically polyarteritis nodosa (PAN)-like symptoms. Mutations in CECR1 (cat eye syndrome chromosome region, candidate 1) are responsible for DADA2. Livedoid racemose, lacunar infarct due to involvement in small vessel of the central nervous system, peripheral neuropathy, digital ulcers and loss of fingers are predominantly seen in the disease which could progress to end-stage organ failure and death in some patients. A wide spectrum of severity in phenotype as well as in the age of onset has been reported in the literature. This phenotypic variability is also found in our clinical practice even in patients with the same mutation. Here, we present a family diagnosed with DADA2, with the previously reported p.Gly47Arg mutation in CECR1.

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience

Background/aim: Gemcitabine, dexamethasone and cisplatin (GDP) is a well-established salvage regimen for relapsed and refractory lymphomas. In this study, we aimed to share our experience with the patients who received GDP/R-GDP (rituximab-gemcitabine, dexamethasone and cisplatin) for stem cell mobilization. Materials and methods: Data of 69 relapsed and refractory Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients who received GDP/R-GDP as salvage chemotherapy in our center between July 2014 and January 2020 were retrospectively evaluated. After the evaluation of response, 52 patients had a chemosensitive disease and underwent mobilization with GDP/R-GDP plus G­CSF (granulocyte colony-stimulating factor). Collected CD34+ stem cells and related parameters were compared in terms of diagnosis of HL and NHL, early and late stage, patients who did not receive RT and those who received RT, and patients aged under 60 and over 60. Results: On the 15th day on average (range 11­20), a median number of 8.7 × 106 /kg (4.1­41.5) CD34+ stem cells were collected in 51 (98%) of our 52 chemosensitive patients and 1 (2%) patients failed to mobilize. We observed acceptable hematological and nonhematological toxicity. The targeted amount of 2 × 106 /kg CD34+ stem cells was attained by 98% (n: 51) patients, and all of them underwent autologous stem cell transplantation. Moreover, low toxicity profiles provide outpatient utilization option clinics with close follow-up and adequate supportive care. Conclusion: We suggest that GDP/R-GDP plus G-CSF can be used as an effective chemotherapy regimen for mobilizing CD34+ stem cells from peripheral blood in relapsed and refractory lymphoma patients due to low toxicity, effective tumor reduction, and successful stem cell mobilization. It can also be assumed that the GDP mobilization regimen may be more effective, especially in patients with early-stage disease and in HL patients.

Inferior prognosis in poor mobilizing myeloma patients.

INTRODUCTION: Induction treatment followed by autologous stem cell transplantation (ASCT) has been accepted as the standard treatment for multiple myeloma (MM) patients. Granulocyte colony stimulating agent (G-CSF), chemotherapy or agents likes plerixafor are being used for the mobilization of stem cells from bone marrow. In this study, we evaluated the impact of the mobilization methods on the outcome of MM patients after ASCT. METHOD: The data of 205 MM patients who underwent ASCT at our center between December 2009 and January 2019 were retrospectively analyzed. Patients were divided into 2 groups as good mobilizers (patients who were mobilized with G-CSF alone) and poor mobilizers (patients who were failed to mobilize with G-CSF alone and mobilized with G-CSF + cylophosphomide or G-CSF + plerixafor). RESULTS: The median progression free survival (PFS) was 18.27 ± 3.22 months in good mobilizers and 14.22 ± 3.7 months in poor mobilizers. In G-CSF + cyclophosphamide method median PFS was 15.4 ± 4.9 months wheras it was only 4 months in G-CSF + plerixafor method. We did not find a statistically significant difference between good and poor mobilizers regarding median PFS (p: 0.342). The median overall survival (OS) was found 34.48 ± 4.2 months in good mobilizers and 15.13 ± 5.78 months in poor mobilizers. In G-CSF + cyclophosphamide method median OS was 17 ± 14.01 months wheras it was 10.66 ± 7.68 months in G-CSF + plerixafor method. We found a statistically significant difference between good and poor mobilizers regarding median OS (p: 0.007*). CONCLUSION: Our study shows that difficulty in stem cell mobilization is correlated with worse outcome.

The effect of serum vitamin B12, folate, ferritin levels and transferrin saturation on stem cell mobilization in allogeneic donors.

INTRODUCTION: Peripheric blood derived stem cells are used in 75 % of allogeneic stem cell transplantations. Iron, vitamin B12 and folate involve in hematopoiesis. Therefore serum levels of iron, vitamin B12 and folat may effect stem cell mobilization. We aimed to analyze the effects of iron status, vitamin B12 and folate levels on peripheric blood stem cell mobilization in healthy donors. METHOD: The mobilization results of 218 allogeneic donors were analyzed retrospectively. RESULTS: In 64 donors, serum ferritin level was <15 µg / L and transferrin saturation was <20 %. When we compared the donors with iron deficiency to the donors without iron deficiency, the number of collected CD34 + cell was significantly higher in donors without iron deficiency. We did not find any impact of serum vitamin B12 and folate level on CD34+ cells collected. CONCLUSION: Our study shows that serum ferritin and transferrin saturation have a greater effect on the amount of CD34+ cells collected from donors than serum vitamin B12 and folate levels. Consequently, when compliance tests of allogeneic donors are performed, the evaluation of vitamin B12 and folate levels is not necessary; whereas iron deficiency must be assessed and -if possible- corrected before apheresis is performed.

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.

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.

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.

Bag-1 stimulates Bad phosphorylation through activation of Akt and Raf kinases to mediate cell survival in breast cancer.

BACKGROUND: Bag-1 (Bcl-2-associated athanogene) is a multifunctional anti-apoptotic protein frequently overexpressed in cancer. Bag-1 interacts with a variety of cellular targets including Hsp70/Hsc70 chaperones, Bcl-2, nuclear hormone receptors, Akt and Raf kinases. In this study, we investigated in detail the effects of Bag-1 on major cell survival pathways associated with breast cancer. METHODS: Using immunoblot analysis, we examined Bag-1 expression profiles in tumor and normal tissues of breast cancer patients with different receptor status. We investigated the effects of Bag-1 on cell proliferation, apoptosis, Akt and Raf kinase pathways, and Bad phosphorylation by implementing ectopic expression or knockdown of Bag-1 in MCF-7, BT-474, MDA-MB-231 and MCF-10A breast cell lines. We also tested these in tumor and normal tissues from breast cancer patients. We investigated the interactions between Bag-1, Akt and Raf kinases in cell lines and tumor tissues by co-immunoprecipitation, and their subcellular localization by immunocytochemistry and immunohistochemistry. RESULTS: We observed that Bag-1 is overexpressed in breast tumors in all molecular subtypes, i.e., regardless of their ER, PR and Her2 expression profile. Ectopic expression of Bag-1 in breast cancer cell lines results in the activation of B-Raf, C-Raf and Akt kinases, which are also upregulated in breast tumors. Bag-1 forms complexes with B-Raf, C-Raf and Akt in breast cancer cells, enhancing their phosphorylation and activation, and ultimately leading to phosphorylation of the pro-apoptotic Bad protein at Ser112 and Ser136. This causes Bad's re-localization to the nucleus, and inhibits apoptosis in favor of cell survival. CONCLUSIONS: Overall, Bad inhibition by Bag-1 through activation of Raf and Akt kinases is an effective survival and growth strategy exploited by breast cancer cells. Therefore, targeting the molecular interactions between Bag-1 and these kinases might prove an effective anticancer therapy.

Comparison of Clinical and Hematological Parameters of Janus Kinase 2, Calreticulin or Myeloproliferative Leukemia Virus Oncogene Mutant Essential Thrombocythemia and Triple-Negative Essential Thrombocythemia.

Introduction Essential thrombocythemia (ET) is one of the chronic myeloproliferative neoplasms. While Janus kinase 2 (JAK2) V617F mutation is defined in more than half of the patients with ET, calreticulin (CALR) or myeloproliferative leukemia virus oncogene (MPL) mutations are encountered more rarely. The discovery of the JAK2 V617F mutation in 2005, followed by the recognition of MPL and CALR mutations, brought up the idea of subdividing ET according to the mutation status. Our aim in this study is to investigate whether genetic mutations detected in patients diagnosed with ET cause a different clinical phenotype compared to triple-negative ET. Methods This retrospective study was conducted by evaluating the patients who were followed up with the diagnosis of ET in the hematology clinic of two tertiary centers in Turkey between 2009 and 2021. Patients with negative JAK2, CALR, and MPL mutations and meeting the diagnostic criteria for ET were defined as triple-negative ET. The patients were divided into two groups as triple-negative ET and mutation-positive ET according to the presence of a mutation. It was investigated whether there was a difference between these two groups in terms of demographic, laboratory, and clinical characteristics. Results A total of 109 patients were included in the study. The mean age of these patients was 54 (18-91) years and 85 (78%) patients were females. A total of 48 patients (44.0%) had JAK2 mutation, six (5.5%) had CALR mutation, and one (0.9%) had MPL mutation. It was observed that there was a significant difference between the two groups in terms of gender, mean age, and hemoglobin value. While 87% of patients with triple-negative ET were females, this rate was 69% in patients with mutation-positive ET (p = 0.036). The mean age was 41.8 years in triple-negative ET and 67.1 years in patients with mutation-positive ET (p = 0.0001). While the mean hemoglobin value was 12.9 g/dl in patients with triple-negative ET, it was 14.4 g/dl in patients with mutation-positive ET (p = 0.0001). Conclusion It has been observed that ET with JAK2, CALR, or MPL mutations may have different phenotypic features compared to triple-negative ET, resulting in a clinical condition consisting of older patients with a higher erythrocyte count.

COVID-19 PCR test performance on samples stored at ambient temperature.

The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short time period since it was detected in Wuhan. The outbreak required the screening of millions of samples daily and overwhelmed diagnostic laboratories worldwide. During this pandemic, the handling of patient specimens according to the universal guidelines was extremely difficult as the WHO, CDC and ECDC required cold chain compliance during transport and storage of the swab samples. The aim of this study was to compare the effects of two different storage conditions on the COVID-19 real-time PCR assay on 30 positive nasopharyngeal and/or oropharyngeal samples stored at both ambient temperature (22 ± 2 °C) and +4 °C. The results revealed that all the samples stored at ambient temperature remain PCR positive for at least six days without any false-negative result. In conclusion, transporting and storing these types of swab samples at ambient temperature for six days under resource-limited conditions during the COVID-19 pandemics are acceptable.

Concurrent Pathogenic Variants of BRCA1, MUTYH and CHEK2 in a Hereditary Cancer Family.

Concurrent pathogenic variants (PVs) in cancer predisposition genes have been reported in 0.1-2% of hereditary cancer (HC) patients. Determining concurrent PVs is crucial for the diagnosis, treatment, and risk assessment of unaffected family members. Next generation sequencing based diagnostic tests, which are widely used in HCs, enable the evaluation of multiple genes in parallel. We have screened the family members of a patient with bilateral breast cancer who was found to have concurrent PVs in BRCA1 (NM_007294.3;c.5102_5103del, p.Leu1701Glnfs*14) and MUTYH (NM_001128425.1;c.884C>T, p.Pro295Leu). Further analysis revealed concurrent PVs in CHEK2 (NM_007194.4;c.1427C>T, p.Thr476Met) and MUTYH (NM_001128425.1;c.884C>T, p.Pro295Leu) in the maternal uncle of the index case. Eight additional family members were found to have PVs in BRCA1 and MUTYH among 26 tested relatives. The sister and the brother of the index case who were diagnosed with breast and colon cancers, respectively, presented with the same genotype as the index case. Each family member was evaluated individually for clinical care and surveillance. This is the first report describing a family with BRCA1, MUTYH and CHEK2 concurrent PVs. Our findings provide valuable information for the assessment and management considerations for families with concurrent PVs.

Determining the accuracy of next generation sequencing based copy number variation analysis in Hereditary Breast and Ovarian Cancer.

BACKGROUND: Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA). RESEARCH DESIGN AND METHODS: In total, 1276 cases were studied by targeted NGS panels and 691 cases (61 calls in 58 NGS-CNV positive and 633 NGS-CNV negative cases) were validated by MLPA. RESULTS: Twenty-eight (46%) NGS-CNV positive calls were consistent, whereas 33 (54%) calls showed discordance with MLPA. Two cases were detected as SNV by the NGS and CNV by the MLPA analysis. In total, 2% of the cases showed an MLPA confirmed CNV region in BRCA1/2. The results of this study showed that despite the high false positive call rate of the NGS-CNV algorithm, there were no false negative calls. The cases that were determined to be negative by the NGS and positive by the MLPA were actually carrying SNVs that were located on the MLPA probe binding sites. CONCLUSION: The diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.

Could blood groups have prognostic significance on survival in patients with diffuse large B cell lymphoma?

The prognostic importance of the ABO blood group in non-Hodgkin lymphoma is largely unknown. We aim to investigate the prognostic significance of blood groups on the survival in diffuse large B-cell lymphoma (DLBCL) patients. 412 people (206 DLBCL patients and 206 healthy donors) were included. The blood group types of patients treated at our center from 2009 to 2019 were analyzed retrospectively and compared to the results from healthy thrombocyte donors. The distribution of the ABO blood groups was as follows: blood type A (45.2%), B (9.7%), O (38.8%), and AB (6.3%). We found no statistically significant difference between patients and the control group in terms of ABO and Rhesus blood group distribution (p = 0.27 and p = 0.45, respectively). The median follow-up time was 18 months (0-116). In the Cox regression analysis ABO blood groups, and Rh group were not significant predictors of survival in patients with DLBCL, whereas ECOG score, IPI score, Ann-Arbor stage, and LDH level were found significant. Receiving R-CHOP as the first-line treatment was associated with better survival in the multivariate analysis. No statistically significant difference was found between the control and DLBCL patient groups regarding the distribution of ABO and Rh blood groups.

Does sampling saliva increase detection of SARS-CoV-2 by RT-PCR? Comparing saliva with oro-nasopharyngeal swabs.

The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in the nasopharyngeal sample by RT-PCR. Recently, saliva samples have been suggested as an alternative sample. In the present study, we aimed to compare RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. On day 0, at least one sample was positive in 67 % of 98 patients. The positivity rate was 83 % for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63 % for saliva samples (p < 0.001). On day 5, RT-PCR was performed in 59 patients, 34 % had at least one positive result. The positivity rate was 55 % for both saliva and nasopharyngeal samples, while it was 60 % for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at the early stages of infection. However, on the 5th day, viral RNA detection rates in saliva were similar to nasopharyngeal and oro-nasopharyngeal samples. In conclusion, we suggest that, in patients receiving treatment, RT-PCR in saliva, in addition to the standard samples, is important to determine the isolation period and control transmission.

The Outcome of Diffuse Large B Cell Lymphoma Patients in Adolescent and Young Adult Age Group.

Purpose: In the literature, substantial differences have been reported regarding incidence and outcomes for the pediatric and adult groups with non-Hodgkin's lymphoma (NHL). Diffuse large B cell lymphoma (DLBCL) is the most common NHL subtype, and its outcome in adolescents and young adults (AYA) has not been widely investigated. This study aims at reporting our experience on the outcome of DLBCL in the AYA group. Methods: One hundred twenty DLBCL patients, 40 AYA patients, and 1:2 matched 80 control non-AYA patients were diagnosed and followed up at our center included. Results: In both groups, the median progression-free survival (PFS) and overall survival (OS) were not reached, without any difference between groups (p = 0.7, p = 0.7, respectively). The median follow-up time was 28 (range 1-133) months in all patients. In both groups, international prognostic index scores and early relapse were associated with worse PFS and OS, but in the non-AYA group, the immunohistologic type was, in fact, related to worse outcomes. Conclusion: DLBCL in AYA is a predominantly overlooked subject, due to the rarity of the disease. The outcome of DLBCL in this age group is not encouraging, which not only needs to be further investigated, but novel approaches must also be developed.

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.

Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) has an increasing incidence in elderly patients with poorer prognosis than in younger patients. Clinicians should clearly identify the characteristics and prognostic factors of elderly patients. We analyzed the outcome of elderly DLBCL patients, especially factors affecting survival in real-life clinical practice. MATERIALS AND METHODS: The data of 330 DLBCL patients at our center were retrospectively evaluated by dividing three groups; younger than 65 years, between 65-79 years, and 80 years and older. We examined the factors affecting survival in DLBCL patients ≥ 65 years old. RESULTS: The median age of the patients was 61 years (range 16-87). 192 (58.2 %) of our patients were younger than 65 years old, 112 (33.9 %) were between 65-79 years, and 26 (7.9 %) patients were 80 years old or older. The median follow-up was 15 (1-120) months. Median PFS was 38 months in the 65-79 years group, ten months in the ≥ 80 years group; meanwhile, median OS was 43 months in the 65-79 years group, 25 months in the ≥80 years group. The number of patients who relapsed within 12 months of the first-line treatment was 69 (35.9 %) in the <65 years group, it was 60 (53.6 %) in 65-79 years group, and 22 (84.6 %) in ≥80 years group (p < 0.001). The median OS was 9 (7.1-10.9) months in DLBCL patients older than 65 years old who relapsed within 12 months. Early relapse, failure to achieve CR after first-line chemotherapy, and high IPI score were associated with poor survival in patients ≥ 65 years old (p:0.001). CONCLUSION: Advancing age was a poor prognostic factor for survival of DLBCL. Relapsing within the first year, or failure to achieve complete remission were associated with poorer survival of the elderly DLBCL patients. R-CHOP is the standard treatment in DLBCL, and the best responses are obtained regardless of age. Due to difficulty in receiving standard treatments, novel treatment modalities are needed for better outcomes in elderly patients with DLBCL.

The musculoskeletal system manifestations in children with familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of self-limiting fever and inflammation of serosal membranes. Besides the findings in the diagnostic criteria, musculoskeletal findings can also be seen in FMF patients attacks. In this study, we aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF. METHODS: The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least six months in our pediatric rheumatology clinic were included in this study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the "Mediterranean Fever" (MEFV) gene variants. Musculoskeletal manifestations of the patients were compared between the groups. RESULTS: The study group included 634 children with FMF (336 female and 298 male, F/M: 1.13/1). The clinical manifestations of patients in the attack period were as follows: 99% of the patients had a fever, 87.3% had abdominal pain, 20.7% had chest pain, 11.3% had vomiting, 10.7% had erysipelas like erythema, and 9.3% had a headache. The musculoskeletal symptoms were accompanied by 58.6% (n=372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n=206). Also, the other musculoskeletal manifestations were as follows during attacks: arthritis in 23.7% (n=150), myalgia in 20.5% (n=130), exertional leg pain in 6.5% (n=41), and protracted febrile myalgia in 1% (n=7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variants in exon-10 (p=0.017). The musculoskeletal manifestations were more common in the attack periods of patients carrying the M694V variant in at least one allele (p=0.019). CONCLUSION: We found that the musculoskeletal manifestations were accompanied in more than half of patients with FMF. M694V variant was found as a risk factor for emerging musculoskeletal manifestations.