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Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 10 6 /kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 10 6 /kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction/background: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings., Patients/methods: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers., Results: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p + /p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS., Conclusion: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings., Competing Interests: None., (AJBR Copyright © 2021.)

Autologous stem cell transplantation (ASCT), supported by high-dose chemotherapy, is the prevalent option for multiple myeloma (MM) treatment in candidates suitable for transplantation. Although granulocyte colony-stimulating factor (G-CSF) supported cyclophosphamide (CY) is used as the pre-ASCT mobilization regimen, there is no consensus on the optimal dosage of CY. Thus, in this study, we examined the results of 47 MM patients, who underwent ASCT after mobilization with intermediate (ID) or low-dose (LD) CY treatment supported with G-CSF. As the mobilization regimen, we used ID (2.4 g/m 2 ) of CY in 22 patients, and LD (1 g/m 2 ) of CY in 25 patients. Adequate doses of CD34+ cells were collected in both groups. At the same time, febrile neutropenia was observed to be less common in patients in the LD-CY group. Additionaly 96% of patients in LD-CY group did not need to be hospitalized during the mobilization. In conclusion, we think that mobilization with LD-CY and G-CSF is advantageous since it results in a sufficient amount of stem cells in addition to being advantageous in terms of patient safety and cost., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty-three patients were included in the study. Median age of patients was 37.5 years (18-70) at the time of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and remaining 39.5% had stage III and IV disease. Median follow-up was 46 months. During follow-up, none of the patients died. Seven patients relapsed or progressed after initial therapy at a median of 12 months. Five of 7 relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP, ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of relapsed/refractory patients were able to achieve complete remission after salvage therapy. Lactate dehydrogenase levels were significantly higher in patients with progressive disease compared with nonprogressive disease. Our study showed an excellent outcome with all patients alive at last contact with a median follow up of 46 months despite a wide range of different therapeutic approaches. All relapsed and refractory patients were successfully salvaged despite a low frequency of patients received immunotherapy in conjunction with chemotherapy. Our results suggest that immunotherapy may be reserved for further relapses., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: The aim of this study was to investigate the rate of carbapenem-resistant gram-negative bacilli (CRGNB) colonization and to analyze the risk factors associated with CRGNB colonization., Methods: This prospective study was conducted in adult patients hospitalized in hematopoietic stem cell transplantation (HSCT) units over a period of 8 months. Rectal swab samples were obtained from each participant every Monday, and patients CRGNB positive on admission were excluded., Results: Of 185 participants, the median age was 47 years, and 59.5% were men. CRGNB colonization was detected in 21 (11.4%) patients. The most commonly isolated CRGNB were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Multivariate analysis revealed that busulfan use (11.9 times), fludarabine use (6.4 times), transfer from another hospital (7.8 times), transfer between units (9.3 times), and central venous catheterization (5.1 times) were risk factors for CRGNB colonization. During the study period, febrile neutropenia (FN) developed in 9 (56.2%) of the 21 colonized patients, and 1 patient died., Conclusions: Screening of patients for CRGNB colonization may have a role in preventing the spread of CRGNB. However, the empirical antimicrobial treatment for FN in patients with CRGNB colonization did not change, and their mortality rates were similar., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

PNH Education and Study Group (PESG) have been established in December 2013 as a non-profit, independent, medical organization www.pesg.org. Paroxysmal Nocturnal Hemoglobinuria (PNH) is a multi-systemic disease that should be treated with a multidisciplinary approach. Patients may apply to the clinics other than the hematology due to variability and diversity of clinical findings which lower the rate of diagnosis due to low awareness about PNH. PNH might be overlooked and diagnosis might be delayed. Regarding these, PESG was established with the collaboration of Immunology, Cardiology, Thorax Diseases (Pulmonology), Neurology, Gastroenterology, General Surgery and Urology specialists in addition to hematologists dealing with PNH. The PESG study group aims to increase the awareness about PNH, including training activities about PNH, strengthening the relations between clinics and planning of clinical studies as a goal. It is the first professional organization focusing on PNH, in Turkey.In this guideline, we want to facilitate the diagnosis attributes of physicians from all specializations that deal with PNH and its systemic complications. One can perceive this as a tailor made guideline of international guidelines but not a compilation.

We aimed to provide real-life information about the effectivity of different types of primary antifungal prophylaxis (AFP) in patients with acute myeloid leukemia (AML). Records of AML patients who received remission-induction chemotherapy between June 2010 and February 2013 were retrospectively reviewed. A total of 85 AML remission-induction chemotherapy cycles were identified in 80 patients. Fluconazole prophylaxis (FP) was administered in 29 cycles, and posaconazole prophylaxis was given in 56 cycles. Failure in the AFP was observed in 45 (57.9 %) out of 85 cycles. Any type of invasive fungal diseases were detected in 15 (26.8 %) out of 56 cycles receiving posaconazole and 15 (51.7 %) out of 29 cycles receiving fluconazole (p = 0.023). Relapsing or refractory AML, longer duration of neutropenia and FP were more common in patients with AFP failure. Multivariate logistic regression analysis showed that type of AFP (odds ratio (OR) 3.63; 95 % confidence interval (CI) 1.19-11.07), presence of neutropenia longer than 21 days (OR 3.96; 95 % CI 1.36-11.46), and refractory or relapsing AML (OR 6.09; 95 % CI 2.09-17.73) were independent factors associated with failure of AFP. We observed superiority of posaconazole on fluconazole in the prophylaxis of AML patients receiving remission-induction chemotherapy.

Aims: We aimed to investigate whether older age leads to limitations in the starting dose of imatinib in daily treatment of chronic myeloid leukemia, and to determine the compliance of elderly patients with tyrosine kinase inhibitors (TKI) therapy., Methods: Data including the clinical characteristics, therapeutic outcomes and compliance with TKI therapy of elderly patients with chronic myeloid leukemia aged >65 years were collected from 13 institutions in Turkey, retrospectively., Results: A total of 69 patients (27 [39%] men, 42 [61%] women) were evaluated retrospectively. The median age of the patients was 71 years (range 66-85 years). Of the patients, 66 (96%) were in the chronic phase and three (4.3%) were in the accelerated phase when diagnosed. A total of 63 (91.3%) patients were receiving imatinib as the first-line therapy. The initial dose of imatinib was 400 mg/day in 59 patients (93.6%). Imatinib treatment induced 57 (90.5%) complete hematological responses at 3 months, 29 (46%) complete cytogenetic responses at 6 months and 49 (77.7%) major molecular responses at 12 months. As a result, nilotinib and dasatinib were used in 14 patients as second-line therapy. Second-line TKI induced nine complete hematological responses (64.3%) at 3 months, four complete cytogenetic responses (28.6%) at 12 months and seven major molecular responses (50%) at 18 months. A total of 56 of the patients (81.2%) are still alive. The median overall survival and progression-free survival rates were 35 months (range 1-95 months) and 17 months (range 0.8-95 months), respectively., Conclusion: Elderly patients should receive TKI according to the same guidelines that apply to younger patients., (© 2014 Japan Geriatrics Society.)

Iron overload increases the risk of infections, veno-occlusive disease and hepatic dysfunction in post-transplant period. Our objective was to investigate the association of pre-transplant ferritin levels with complications and survival after allogeneic hematopoietic stem cell transplantation (alloHSCT).We retrospectively analysed 84 patients' data who had undergone allogeneic HSCT into two groups: patients with a serum ferritin level ≥ 1000 ng/ml, and patients with <1000 ng/ml at the time of HSCT.Cox-regression analysis showed that pre-transplant serum ferritin levels were significantly higher in patients who had at least one infectious event compared with those who had no any infectious event in the post-transplant 100 days (p<0.023). Overall survival (OS) and disease-free survival (DFS) rates were significantly higher in patients with a time-to-tx interval 12 months (p=0.002 and p=0.008 respectively). A higher risk of death was observed in high-ferritin group (hazard ratio=2.27, CI:1.01-5.09, p=0.023 for OS and hazard ratio=2.49, CI:1.12-5.53 p=0.039 for DFS). No significant effect on OS and DFS among groups was observed for variables conditioning regimen, gender and diagnosis. Acute GVHD was more common in patients with a ferritin level ≥ 1000 ng /mL, but this was not statistically significant (p>0.05). There was no statistical significance in both groups (ferritin ≥ 1000 ng /mL and ferritin <1000 ng/mL) for relapse rates (p>0.05). Platelet and neutrophil engaftment day was not found statistically significant compared with both groups (p=0.273 and p=0.882, respectively). Pre-transplant ferritin levels may predict poor outcomes in patients who had undergone allogeneic hematopoietic stem cell transplantation.