Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Effects of cytokine hemadsorption as salvage therapy on common laboratory parameters in patients with life-threatening COVID-19.

BACKGROUND: The COVID-19 pandemic has led to emergency approval of treatment modalities unusual for viruses, such as therapeutic cytokine Hemadsorption(HA). This study aims to investigate the experience of salvage HA therapy and the effect of HA on routine laboratory tests. METHODS: Life-threatening COVID-19 patients followed up between April 2020 and October 2022 who underwent HA salvage therapy were retrospectively enrolled. Data derived from the medical records were evaluated to meet the assumptions of statistical tests, and those that met the relevant statistical rules were selected for further analysis. Tests of Wilcoxon, Paired-T, and repeated measures-ANOVA were used to analyse the laboratory tests performed before and after HA among the surviving and nonsurviving patients. P < 0.05 was selected for the statistical significance of the alpha. RESULTS: A total of 55 patients were enrolled in the study. Fibrinogen (p = 0.007), lactate dehydrogenase (LDH) (p = 0.021), C-reactive protein (CRP) (p < 0.0001), and platelet (PLT) (p = 0.046) levels showed a significant decrease with the HA effect. WBC (p = 0.209), lymphocyte (p = 0.135), procalcitonin (PCT) (p = 0.424), ferritin (p = 0.298), and D-dimer (p = 0.391) levels were not affected by HA. Ferritin level was significantly affected by survival status (p = 0.010). All patients tolerated HA well, and 16.4 % (n = 9) of the patients with life-threatening COVID-19 survived. CONCLUSION: HA is well tolerated even when used as a last option. However, HA may not affect WBC, lymphocyte, and D-dimer levels. In contrast, the effect of HA could limit the benefits of LDH, CRP, and fibrinogen in various clinical assessments. This study suggests that HA treatment could be beneficial even if selected as a salvage therapy.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Does ferritin level affect the outcomes of autologous stem cell transplantation equally in all diseases?

BACKGROUND: In this retrospective study, we evaluated the effect of ferritin levels on the outcomes of autologous stem cell transplantation in patients with MM or lymphoma. METHODS: In this study, 170 patients with measured ferritin levels within one month before transplantation who underwent ASCT with the diagnosis of MM or lymphoma were evaluated. The cut-off value of ferritin was determined as 500 ng/mL to evaluate the transplant outcomes in both groups. The hematological recovery status/duration, febrile neutropenia rate, hospitalization time, transplant-related mortality (TRM) in the first 100 days, and OS were evaluated according to the ferritin level RESULTS: Of all patients, 105 (61,8%) were diagnosed with MM and 65 (38.2%) with lymphoma. Ferritin levels had no statistically significant effect on the engraftment status/times, the febrile neutropenia rates, and hospitalization times of both lymphoma and myeloma patients (p > .05). Ferritin level was not significantly associated with TRM in MM (p = .224). However, in lymphoma, ferritin level was significantly associated with TRM (33.3% for ferritin level ≥500 ng/L vs. 5.3% for ferritin level ng/mL, p = .005). There was no statistically significant correlation between ferritin value and OS in MM group [ferritin level ≥ 500 ng/L: 39.9 months (95% CI: 33.7-46.1) and ferritin level 500 ng/mL: 39.4 months (95% CI: 36.5-42.2), p = .446]. Ferritin level was significantly associated with OS in patients with lymphoma [ferritin level ≥ 500 ng/L: 22.1 months 95% CI: 14.7-29.5), ferritin level 500 ng/mL: 27.3 months (95% CI: 22.4-32.2), p = .038] CONCLUSION: High ferritin level is important prognostic factor on survival after ASCT in patients with lymphoma.

Solitary Plasmacytoma in a Patient Presenting with Taste Disturbance.

Solitary plasmacytoma is a disease included in plasma cell dyscrasias, presenting outside of the bone marrow, and with the potential to turn into multiple myeloma. A 66-year male patient was admitted to the hematology clinic with the complaint of impaired taste. Physical examination revealed edema of the left pharynx. After excisional tissue biopsy, serum/urine protein electrophoresis, and immunofixation tests of the patient diagnosed with plasmacytoma were negative. An increase in atypical plasma cells was noted on bone marrow aspiration and biopsy. There was no systemic involvement outside the pharynx on the PET-CT examination. He was referred to the radiotherapy department for further management. Since the affected area is frequently the nasopharynx, sinuses, and larynx in extramedullary solitary plasmacytoma cases, they generally presented to the clinic with difficulty in swallowing, shortness of breath and pain symptoms. This case presented with a non-specific complaint of taste disturbance along with difficulty in swallowing. Key Words: Plasmacytoma, Nasopharynx, Multiple myeloma.

The effect of G-CSF used after allogeneic hematopoietic stem cell transplantation on engraftment times and platelet suspension replacement numbers.

BACKGROUND: With the use of granulocyte colony stimulating factor (G-CSF) after allogeneic hematopoietic stem cell transplantation (HSCT), the duration of neutrophil engraftment and hospitalization were shortened. However, there is no consensus on the effect of G-CSF on platelet engraftment time. The primary aim of our study is to determine the effect of G-CSF use on platelet engraftment time after HSCT. Secondary purposes are to determine the number of platelet suspension, number of erythrocyte suspension and incidence of acute graft versus disease after HSCT. MATERIAL AND METHODS: Patients who had allogeneic stem cell transplantation at our center between 01.01.2011 and 01.01.2022 were retrospectively analyzed. Patients were divided into 2 groups as those who received and did not receive G-CSF after transplantation. RESULTS: A total of 64 patients were included. While 32 patients were given post-HSCT G-CSF support, the other 32 patients were not given. Neutrophil engraftment time and length of hospital stay were shorter in the group receiving G-CSF (p < 0.05). Platelet engraftment time was shorter in the group that did not receive G-CSF (p < 0.05). The incidence of acute GVHD of the patients in group 1 tended to be higher than the patients in group 2 (40.6 % vs 15.6 %, p = 0.052). Post-HSCT platelet suspension was less in the group that did not receive G-CSF, but this difference was not statistically significant (p = 0.173). CONCLUSION: While the positive effect of post HSCT G-CSF use on duration of neutrophil engraftment and hospitalization is evident, its effects on platelet engraftment need to be investigated.

Phonetic complexity and stuttering in Turkish-speaking children who stutter.

The relationship between stuttering and phonetic complexity for words spoken by Turkish children who stutter was investigated. The research questions were: (1) Do Turkish-speaking children stutter more on unbound content words than on unbound function words? (2) Do Turkish-speaking children stutter more on words with higher phonetic complexity scores? Twenty-one monolingual children aged 6-11 years who had a clinical diagnosis of stuttering participated. Speech samples were transcribed and lexical categories determined. Phonetic complexity was assessed by an adaptation of Index of Phonetic Complexity (IPC) for Turkish. Results revealed that the mean rank of unbound content words differed significantly from the mean rank of unbound function words and that stuttering frequency for unbound content words was significantly higher than for unbound function words.

Reliability and validity of the UTBAS-TR (The Unhelpful Thoughts and Beliefs Scale-the Turkish version) in the Turkish population.

Purpose: This paper decribes the development of the Turkish adaptation of UTBAS (UTBAS-TR) and reports the results concerning its applicability and psychometric structure.Method: The sample consisted of 81 males and 19 females diagnosed with developmental stuttering in two centres. Test-retest reliability score was obtained by correlating results of repeated aplications of the scale within a one-week interval and a paired t-test was calculated to see the differences in the total and UTBAS I, II and III scores. The internal consistency was assessed using the Cronbach's alpha. Construct validity was also assessed by examining inter-scale correlations and with the correlations of the UTBAS-TR with two other scales (State-Trait Anxiety Inventory (STAI) and Beck Anxiety Inventory (BAI)).Result: The internal consistency of the UTBAS-TR and the test and retest reliability score was statiistically significant. The correlation between UTBAS-TR total score and the UTBAS-TR I, II and III correlations were high. A significant correlation was observed between UTBAS-TR total score with State Anxiety Inventory. However, the correlations between UTBAS-TR-Total Score and Trait Anxiety Inventory and Beck Anxiety Inventory were low.Conclusion: The UTBAS-TR proved to be suitable for use with the Turkish population.

Splenic Marginal Zone Lymphoma in Turkey: Association with Hepatitis B Instead of Hepatitis C Virus as an Etiologic and Possible Prognostic Factor - A Multicenter Cohort Study

Objective: Chronic antigenic stimulation is frequently blamed in the pathogenesis of extranodal marginal zone lymphomas including splenic marginal zone lymphoma (SMZL). Chronic hepatitis C is frequently observed in SMZL patients in some geographical regions. However, these reports are largely from North America and Europe, and data from other countries are insufficient. In this multicenter study we aimed to identify the clinical characteristics of SMZL patients in Turkey, including viral hepatitis status and treatment details. Materials and Methods: Data were gathered from participating centers from different regions of Turkey using IBM SPSS Statistics 23 for Windows. Hepatitis B virus surface antigen (HBsAg), anti-HBs antibody, anti-HB core antigen antibody (anti-HBcAg), HB viral load, anti-hepatitis C virus (HCV) antibody, HCV viral load results were analyzed. Results: One hundred and four patients were reported. Hepatitis C virus positivity was observed in only one patient. However, hepatitis B virus surface antigen (HBsAg) positivity was observed in 11.2% and HBsAg and/or anti-HB core antigen antibody (anti-HBcAg) positivities were seen in 34.2% of the patients. The median age was 60 years (range=35-87). Median follow-up duration was 21.2 months (range=00.2-212; 23.2 months for surviving patients). Median overall survival was not reached. Estimated 3-year and 10-year survival rates were 84.8% and 68.9%, respectively. Older age, no splenectomy during follow-up, platelet count of <90x103/µL, lower albumin, higher lactate dehydrogenase, higher ß2-microglobulin, and HBsAg positivity were associated with increased risk of death. Only albumin remained significant in multivariable analysis. Conclusion: These results indicate that hepatitis B virus may be a possible risk factor for SMZL in our population. It may also be an indirect prognostic factor.

Efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/ refractory multiple myeloma: a real-life experience

Background/aim: In Turkey, lenalidomide plus dexamethasone (RD) has been used to treat relapsed/refractory multiple myeloma (RRMM) since 2010. This retrospective, single-center study evaluated the efficacy and tolerability of RD in patients with RRMM between October 2010 and June 2016. Materials and methods: Patients' records were reviewed, and overall (OS) and progression-free survival (PFS) were assessed. Results: One hundred and twenty patients (71 males; 59.2%) were included in the study. The median number of prior lines of treatment was one (1­4); 72 patients (60.0%) received RD as second-line therapy and 51 patients (42.5%) had previously undergone autologous stem cell transplantation (ASCT). The overall response rate was 72.5%, with 19% of these patients achieving a complete response. The median length of follow-up and duration of response to RD was 14 months and 19 months, respectively. Median OS and PFS were 32 and 21 months, respectively. Prior ASCT, an overall response, and treatment with RD for >12 cycles were identified as independent prognostic factors for OS and PFS. Adverse events (AEs) occurred in 69 (57.5%) and 14 patients (11.7%) discontinued treatment due to AEs. Conclusion: We found RD to be safe, well tolerated, and effective in RRMM in everyday clinical practice in Turkey.

Carfilzomib experience in relapsed/refractory multiple myeloma: a single-center experience

Background/aim: Carfilzomib (CFZ) is a new-generation proteasome inhibitor with significant activity in relapsed or refractory multiple myeloma (R/R-MM). We have retrospectively evaluated R/R-MM patients who were treated with CFZ plus dexamethasone. Materials and methods: Twenty-one R/R-MM patients who were treated with CFZ plus dexamethasone between October 2013 and January 2016 were screened. The patients were followed until March 2016 after CFZ treatment. Results: Ten (47.6%) of the patients were female and 11 (52.4%) of them were male. The median age was 62 (47-76) years. The median number of prior treatment lines was 3 (2-7). The median number of administered cycles of treatment for CFZ was 4 (1-10). The median overall response rate was 26.3%. The most common hematological adverse events were anemia and thrombocytopenia (38%). The most common nonhematological adverse event was fatigue (71.4%). One patient died because of a cerebrovascular event and 1 patient died because of pneumonia during the treatment period. The median duration of response rate and time to next therapy were 8 (7-9) and 3 (2-16) months, respectively. The median overall survival was 8 (0.5-33) months. Conclusion: Despite the small number of patients, our results suggest that CFZ provides acceptable responses in heavily pretreated R/R-MM patients.

Use of Tigecycline for Diabetic Foot Infections

OBJECTIVE: The aim of this study is to evaluate tigecycline for diabetic foot infections (DFIs). MATERIALS AND METHODS: In this prospective observational study, the investigators included patients who had consultation with the Diabetic Foot Council of Ege University Faculty of Medicine (Izmir, Turkey) between March 2013 and July 2015 and who used tigecycline during their treatment. Treatment success was assessed by design-specific criteria for each evaluation. RESULTS: The study included 105 cases. Of those, 37 (35.2%) were women (mean [± standard deviation] age, 61.9 ± 11.9 years). The success rate of tigecycline treatment was 93.3% in mild infections, 56.2% in moderate, 57.7% in severe, and 61.9% in all cases. The authors found a 9-fold decrease (P = .046) in the success of tigecycline treatment among those who developed moderate or severe DFIs and a 6.4-fold decrease (P < .0001) among those who had arterial stenosis. For 33 (71.7%) of 46 (43.8%) patients who experienced a side effect, tigecycline treatment was continued as it could be tolerated. CONCLUSIONS: If tigecycline is to be the treatment choice, extra attention must be paid to patients with arterial stenosis, severe DFIs, and side effects. The common disadvantage is the high side effect rate, especially nausea. However, it is generally not necessary to discontinue the medication in cases with nausea. Therefore, tigecycline may be used as a choice of therapy in mild DFIs.

Risk factors for amputation in patients with diabetic foot infection: a prospective study.

There is a variety of diagnostic and therapeutic algorithms for diabetic foot infections (DFIs). Some of them are too difficult to be applied in routine clinical approach. In the routine clinical approach, it is necessary to find new risk factors and end up with a quick and easy assessment of DFIs. In this study, we aimed to evaluate the independent risk factors for osteomyelitis, amputation and major amputation in patients with DFI using standard scoring procedures. We prospectively studied 379 patients with DFI. The variables were analysed using logistic analysis. A total of 126 cases (33·2%) underwent amputation. The odds ratios in the amputation model were 3·09 for osteomyelitis (P < 0·001), 4·90 for arterial stenosis (AS) (P < 0·001), 3·67 for the history of DFI (P = 0·001), 2·47 for ulcer duration >60 days (P = 0·001), 3·10 for ulcer depth > 15 mm (P < 0·001) and 10·28 for fungal DFI (P = 0·015). In this study, the unusual result of well-known literature was fungal DFI as an independent risk factor for amputation in patients with DFI.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study.

OBJECTIVE: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. MATERIALS AND METHODS: In this retrospective multicenter study, 130 patients of ≥60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. RESULTS: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. CONCLUSION: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.