Effect of COVID-19 Pandemic on Hematopoietic Stem Cell Transplant Activity: Experience of a JACIE-Accredited Center.

OBJECTIVES: The adoption of international quality and accreditation standards is important for the success of transplant centers. Guidelines from the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE) have enabled quality management of the operations of clinical units of cellular therapy centers, including cell collection and processing, thus minimizing errors and adverse events. COVID-19 has had significant implications for immunocompromised patients, particularly hematopoietic stem cell transplant recipients, as well as their donors and caregivers. Here, we retrospectively examined measures, taken in our transplant center in Turkey during the pandemic period between March 2020 and October 2021, to investigate how JACIE accreditation has affected patient, donor, product, and employee safety. MATERIALS AND METHODS: We analyzed data on transplant activity, as well as donor, patient, product, and employee safety, during the pandemic in 3 separate 6- month periods. The measures were analyzed starting from March 2020, when the first COVID-19 case was seen in Turkey. RESULTS: Since the beginning of the pandemic, 140 patients have undergone stem cell transplant in our center. Stem cell transplant was delayed in 22 patients because of the pandemic. Transplant was also postponed due to COVID-19 positivity in 6 patients, and 2 patients died due to COVID-19 infection during the transplant process. Unrelated donor activity continued to be performed safely throughout this period. COVID- 19 infection developed in 12 of the 52 personnel working in the bone marrow transplant unit, one of whom needed intensive care due to severe pneumonia. In terms of quality management activities, the impact of the pandemic was greatest during the first month. CONCLUSIONS: Results from our retrospective study examining the impact of JACIE accreditation in a stem cell transplant center during the COVID-19 pandemic showed that, when national and international guidelines are followed, JACIE accreditation can facilitate adaptation to changing conditions in transplant centers.

Castleman Disease: A Multicenter Case Series from Turkey

Objective: Castleman disease (CD) is a rare disease also known as angiofollicular lymph node hyperplasia. The two main histological subtypes are the hyaline vascular and plasma cell variants. It is further classified as unicentric CD (UCD) or multicentric CD (MCD) according to the anatomical distribution of the disease and the number of lymph nodes involved. The aim of this multicenter study was to evaluate all cases of CD identified to date in Turkey to set up a national registry to improve the early recognition, treatment, and follow-up of CD. Materials and Methods: Both adult (n=130) and pediatric (n=10) patients with lymph node or involved field biopsy results reported as CD were included in the study. Patients' demographic information, clinical and laboratory characteristics, imaging study results, treatment strategies, and clinical outcomes were evaluated retrospectively. Results: A total of 140 patients (69 male and 71 female) with a diagnosis of UCD (n=73) or MCD (n=67) were included. The mean age was 39 years in the UCD group and 47 years in the MCD group. Female patients were more common in the UCD group. The most common histological subtype was hyaline vascular for both UCD and MCD patients. Asymptomatic patients were more common in the UCD group. Anemia, elevations of acute phase reactants, and hypoalbuminemia were more common in the MCD group. The most commonly used treatment strategies for UCD were surgical excision, rituximab, and radiotherapy, respectively. All UCD patients were alive at a median of 19.5 months of follow-up. The most commonly used treatment strategies for MCD were methyl prednisolone, R-CHOP, R-CVP, and rituximab. Thirteen MCD patients had died at a median of 34 months of follow-up. Conclusion: This study is important in presenting the patient characteristics and treatment strategies for CD from Turkey, with the potential of increasing awareness about CD. Treatment data may help in making decisions, particularly in countries that do not have access to siltuximab. However, larger prospective studies are needed to make definitive conclusions.

Is It Possible to be a Stem Cell Donor for the Second Time: A Single-Center Report of 12 Consecutive Procedures.

OBJECTIVES: The use of unrelated donors as a source of stem cells for patients with blood disorders continues to increase. Approximately 5% to 7% of unrelated stem cell donors are asked to donate stem cells a subsequent time to the same or a different patient. We investigated donors who accepted to be a donor for the second time between 2015 and 2021; donors were evaluated in terms of procedure-related complications, product quality, and donor follow-up in a JACIEaccredited (Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation). MATERIALS AND METHODS: Stem cell collections were performed in accordance with relevant standard operating procedures from healthy volunteer donors. Data on sequence of peripheral blood stem cell, bone marrow, and donor lymphocyte collection procedures; presence of complications during procedures; time between 2 donations; need for granulocyte colonystimulating factor again; and first and second donation types were noted. Data on donor and stem cell products were determined using the hospital information management system. RESULTS: Our study included 12 donors (9 men and 3 women) who donated a second time within the specified date range. In the evaluation of the second donation types, 7 were lymphocyte collection donations, 4 were peripheral blood stem cell donations, and 1 was a bone marrow stem cell donation. In shortterm and long-term follow-ups, there were no complications among the donors. In the second donations, targeted product values were reached. CONCLUSIONS: Although it is safe to have a second donation from a donor for the same patient, collection centers may collect more products than requested from eligible donors.

Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey

Background/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28­87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10­40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 ± 46.79 mm versus 199.49 ± 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1­55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.

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.

Hepatitis B, Hepatitis C, Human immunodeficiency virus and syphilis frequency among blood donors: A single center study.

We aimed to provide updated results for seroprevalence of hepatitis B, hepatitis C viruses while presenting first data for human immunodeficiency virus and syphilis seropositivity amongst blood donors in Adana, Turkey. Screening and confirmatory test results of 62,461 donors were evaluated. HBsAg, anti-HCV, anti-HIV1/2 and syphilis seropositivity was 1.92%, 0.48%, 0.20%, 0.18% respectively, based on screening tests, and 1.66%, 0.05%, 0.003%, 0.10% respectively, according to confirmatory tests. Transfusion-transmitted infections (TTI) was more prevalent in low-educated donors. HBsAg and syphilis seropositivity rates were higher in married subjects. We found that the prevalence of HBV and HCV was significantly decreased in the last two decades in Adana. Importantly, this study provides first data in HIV and syphilis seropositivity rates among blood donors in our region and both HIV and syphilis seroprevalences were found to be low compared to many regions of Turkey. However, considering the fact that increasing number of immigrants may change prevalences and trends of TTI both in Adana and in Turkey, strict monitorization and yearly reporting of TTI rates seem necessary to be able to take proactive measures.

Prognostic importance of single-nucleotide polymorphisms in IL-6, IL-10, TGF-ß1, IFN-γ, and TNF-α genes in chronic phase chronic myeloid leukemia.

The aim of this study was to explore the association between polymorphisms of five cytokine genes and clinical parameters in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) treated with imatinib. We analyzed five cytokine genes (interleukin [IL]-6, IL-10, gamma interferon [IFN-γ], transforming growth factor beta-1 [TGF-ß1], and tumor necrosis factor-alpha [TNF-α]) in 60 cases with Ph+ CML and 74 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer. All data were analyzed using the de Finetti program and SPSS version 14.0 for Windows. No significant differences were detected between the CML group and healthy controls with respect to the distributions and numbers of genotypes and alleles in TNF-α, TGF-ß1, IL-10, and IFN-γ. However, the GG genotype associated with high expression in IL-6 was found to be significantly more frequent in CML as compared to controls (p=0.010). The median follow-up time was 49.3 months (range 6.1-168.4) and the median duration of imatinib treatment was 39.5 months (range 5.2-103.4) for these patients. On multivariateanalysis, only IL-10 GCC/GCC highly produced haplotypes were significantly associated with a shorter event-free survival. The relationship between cytokine genotypes/haplotypes and clinical parameters in CML has not been investigated before. Our results suggest that IL-10 may be a useful marker for CML prognosis and theGG genotype of the IL-6 gene may be associated with susceptibility.

Prevalence of hepatitis B and C viruses in patients with lymphoproliferative disorders.

The etiology of most lymphoproliferative disorders remains unclear, though several hypotheses have been proposed. One of the conjectured mechanisms is infection of a tumor clone by an oncologic virus. Recently, evidence has arisen implicating both hepatitis B and, even more so, hepatitis C viruses in the pathogenesis of lymphoproliferative disease. Based on this information, we surveyed the prevalence of hepatitis B and C virus in patients with lymphoproliferative disease. A total of 334 newly-diagnosed lymphoproliferative disease patients (200 males, 134 females) and 1,014 (133 females, 881 males) healthy controls were randomly recruited from the university blood bank. Serologic evaluation for hepatitis B and C viruses was conducted and confirmed using PCR analyses. Those with hepatitis B and/or C, controls, and subgroups of patients with lymphoproliferative disease were compared using Pearson Chi-square analysis. Among patients with lymphoid tumors, the seropositivity of HbsAg and/or anti-HCV was 8.7% (29/334), and among the controls 6.1% (49/802), however this difference did not achieve statistical significance (P = 0.23, OR: 1.36, 95% CI: 0.82-2.26). We found no significant gender- or age-related differences for either hepatitis B or C seropositivity. There were no significant differences between the seropositivity rates of hepatitis B, C, or both in either NHL or Hodgkin's lymphoma. However, in the diffuse large cell lymphoma and follicular lymphoma subgroups, the HbsAg seropositivity rate was significantly higher than that in the controls (P = 0.017, P = 0.048, respectively), as was the seropositivity rate for hepatitis C in those with diffuse B cell lymphoma versus controls (P = 0.008). We did not identify any significant difference in the combined prevalence of hepatitis B or C seropositivity between patients with lymphoproliferative disorders and controls. However, significant differences were revealed among certain patient subgroups versus the controls. These two viruses could play a role in the development of certain specific lymphoproliferative disorders. Nevertheless, larger epidemiological studies are necessary and should focus, particularly on specific patient subgroups.

Pill esophagitis caused by telithromycin: a case report.

A large number of oral drugs have been reported to cause pillinduced esophagitis in the medical literature. To our knowledge, this is the first reported case in which telithromycin was the cause of pill-induced esophagitis. In this report, we describe a male patient who admitted to the hospital with dysphagia and retrosternal pain after taking telithromycin (Ketek for acute sinusitis. He had a history of swallowing the film tablet with at least a glass of water and lying down immediately after taking the drug. An upper endoscopic examination demonstrated a deep ulceration of 1 cm diameter in the middle of the esophagus surrounded by relatively normal mucosa. Lansoprazole 30 mg was started. His symptoms improved seven days after cessation of the drug. The esophagus was completely normal in control endoscopy after two weeks. Telithromycin may cause esophageal lesions; therefore, patients should be educated by physicians about the drug's side effects and should drink at least 100 ml water after swallowing the medication. Drug administration should be in the upright position.