E-ISSN: 1308-5263
Turkish Journal of Hematology - Turk J Hematol: 41 (1)
Volume: 41  Issue: 1 - 2024
RESEARCH ARTICLE
1. Disseminated Intravascular Coagulation in Acute Promyelocytic Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals
Rushin Patel, Darshil Patel, Mrunal Patel, Jessica Ohemeng-Dapaah, Afoma Onyechi, Zalak Patel, Chieh Yang, Safia Shaikh
doi: 10.4274/tjh.galenos.2024.2023.0479  Pages 1 - 8
Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare.
Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors.
Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC.
Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients’ vulnerability to bleeding events and the need for transfusions.

2. Real-Life Data on the Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: A Single-Center Analysis
Martyna Wlodarczyk, Agata Wieczorkiewicz Kabut, Krzysztof Bialas, Anna Koclega, Izabela Noster, Patrycja Zielinska, Grzegorz Helbig
doi: 10.4274/tjh.galenos.2024.2024.0026  Pages 9 - 15
Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve posttransplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center.
Materials and Methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation.
Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects.
Conclusion: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118- 152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects.

3. Oncolytic Myxoma virus Increases Autophagy in Multiple Myeloma
Alpay Yeşilaltay, Dilek Muz, Berna Erdal
doi: 10.4274/tjh.galenos.2024.2023.0403  Pages 16 - 25
Objective: Multiple myeloma, which affects plasma cells, is the second most common hematological malignancy. Despite the development of new drugs and treatment protocols, patient survival has not reached the desired level. In this study, we investigated the effects of Myxoma virus (MYXV), an oncolytic virus, on autophagy in myeloma cells.
Materials and Methods: We analyzed protein expressions of ATG-5, p62, Beclin-1, LC3B, and the apoptosis marker Bcl-2 as autophagy markers in human U-266 and mouse MOPC-315 myeloma cell lines subjected to different doses of MYXV. In addition, autophagic images of myeloma cells were investigated using transmission electron microscopy (TEM).
Results: In the first 24 h, which is the early stage of autophagy, ATG-5 and Beclin-1 expression levels were increased in the U-266 and MOPC- 315 cell lines in the groups that had received MYXV at a multiplicity of infection of 15. At 48 h, a significant increase was detected in the expression of LC3B, which is a late indicator. Autophagosomes were observed in myeloma cells by TEM.
Conclusion: MYXV shows an antimyeloma effect by increasing autophagy in myeloma cells.

4. Impact of CALR and JAK2V617F Mutations on Clinical Course and Disease Outcomes in Essential Thrombocythemia: A Multicenter Retrospective Study in Turkish Patients
Zehra Narlı Özdemir, Yıldız İpek, Pusem Patir, Gözde Ermiş, Rafiye Çiftçiler, Deniz Özmen, Mehmet Baysal, Vildan Gürsoy, Esra Yıldızhan, Serkan Güven, Tarık Ercan, Tayfun Elibol, Sinan Mersin, Eylem Genç, Eren Arslan Davulcu, Volkan Karakuş, Nergiz Erkut, Gürsel Güneş, Reyhan Diz Küçükkaya, Ahmet Emre Eşkazan
doi: 10.4274/tjh.galenos.2024.2023.0430  Pages 26 - 36
Objective: In this study, we investigated the effects of calreticulin (CALR) and JAK2V617F mutational status on clinical course and disease outcomes in Turkish patients with essential thrombocythemia (ET).
Materials and Methods: Seventeen centers from Türkiye participated in the study and CALR- and JAK2V617F-mutated ET patients were evaluated retrospectively.
Results: A total of 302 patients were included, of whom 203 (67.2%) and 99 (32.8%) were JAK2V617F- and CALR-positive, respectively. CALR-mutated patients were significantly younger (51 years vs. 57.5 years, p=0.03), with higher median platelet counts (987x109/L vs. 709x109/L, p<0.001) and lower median hemoglobin levels (13.1 g/dL vs. 14.1 g/dL, p<0.001) compared to JAK2V617F-mutated patients. Thromboembolic events (TEEs) occurred in 54 patients (17.9%), 77.8% of which were arterial. Compared to CALR mutation, JAK2V617F was associated with a higher risk of thrombosis (8.1% vs. 22.7%, p=0.002). Rates of transformation to myelofibrosis (MF) and leukemia were 4% and 0.7%, respectively, and these rates were comparable between JAK2V617F- and CALR-mutated cases. The estimated overall survival (OS) and MF-free survival of the entire cohort were 265.1 months and 235.7 months, respectively. OS and MF-free survival durations were similar between JAK2V617F- and CALR-mutated patients. Thrombosis-free survival (TFS) was superior in CALR-mutated patients compared to JAK2V617F-positive patients (5-year TFS: 90% vs. 71%, respectively; p=0.001). Age at diagnosis was an independent factor affecting the incidence of TEEs.
Conclusion: In our ET cohort, CALR mutations resulted in higher platelet counts and lower hemoglobin levels than JAK2V617F and were associated with younger age at diagnosis. JAK2V617F was strongly associated with thrombosis and worse TFS. Hydroxyurea was the most preferred cytoreductive agent for patients with high thrombosis risk.

PERSPECTIVE IN HEMATOLOGY
5. Antiphospholipid Syndrome: To Classify or Not to Classify?
Doruk Erkan
doi: 10.4274/tjh.galenos.2024.2024.0003  Pages 37 - 40
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder resulting in thrombosis, microvascular disease, morbidity in pregnancy, and/or non-thrombotic manifestations. The recently introduced 2023 American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, with significantly higher specificity compared to the revised Sapporo criteria, now reflect the current thinking about APS and provide a new foundation for future APS research. The purpose of this short commentary is to discuss the appropriate circumstances under which the 2023 ACR/EULAR classification criteria could be used and to demonstrate how the new criteria can be applied to simple case scenarios.

IMAGES IN HEMATOLOGY
6. The Many Faces of Multiple Myeloma
Asya Tuğçe Bol, Güldane Cengiz Seval, Meral Beksaç, Işınsu Kuzu
doi: 10.4274/tjh.galenos.2023.2023.0183  Pages 41 - 42
Abstract |Full Text PDF

7. Advanced Cutaneous Peripheral T-cell Lymphoma-Not Otherwise Specified with Extensive Ulceronecrotic Dyschromic Plaques and Poor Outcome
Vishnu Sharma, Vansh Bagrodia
doi: 10.4274/tjh.galenos.2023.2023.0222  Pages 43 - 44
Abstract |Full Text PDF

8. Unusual Clasmatosis Morphology
Antonio La Gioia, Miriam Marsano, Fabiana Fiorini
doi: 10.4274/tjh.galenos.2023.2023.0275  Pages 45 - 46
Abstract |Full Text PDF

LETTER TO EDITOR
9. Epithelial Cells or Vascular Smooth Muscle Cells in a Peripheral Blood Smear?
Wei Yang, Yongliang Wang, Wei Pan
doi: 10.4274/tjh.galenos.2024.2023.0399  Pages 47 - 48
Abstract |Full Text PDF

10. The Importance of Rare Genes on the Prognosis of B-cell Acute Lymphoblastic Leukemia
Li Xiang, Yongliang Wang, Wei Pan
doi: 10.4274/tjh.galenos.2024.2023.0400  Pages 49 - 50
Abstract |Full Text PDF

11. Immunoglobulin Replacement Therapy for Hypogammaglobulinemia in Multiple Myeloma Should Not Be Ignored
Qinggang Zhang, Yongliang Wang, Wei Pan
doi: 10.4274/tjh.galenos.2024.2023.0401  Pages 51 - 52
Abstract |Full Text PDF

12. Circulating Monocytes Phagocytosing Lymphocytes in the Small-Cell Variant of T-Cell Prolymphocytic Leukemia
Shuai Zhang, Meng Ma, Yanping Liu, Ying Bu, Zhe Zhang, Yun Zhang
doi: 10.4274/tjh.galenos.2023.2023.0422  Pages 53 - 54
Abstract |Full Text PDF

13. Successful Management of Ibrutinib-Induced Thrombocytopenia in a Patient with Chronic Lymphocytic Leukemia: No Interruption, Only Reduction
Simge Erdem, Meliha Nalçacı
doi: 10.4274/tjh.galenos.2023.2023.0426  Pages 55 - 56
Abstract |Full Text PDF

14. Ibrutinib-Associated Leukocytoclastic Vasculitis in a Patient with Chronic Lymphocytic Leukemia
Ayşe Kaya, İbrahim Aras, Pervin Özkan Kurtgöz, Umut Çakıroğlu
doi: 10.4274/tjh.galenos.2023.2023.0368  Pages 57 - 58
Abstract |Full Text PDF

15. Nilotinib-Associated Multiple Silent Arterial Stenoses in a Patient with Chronic Myeloid Leukemia
Mert Tokatlı, Rashad Ismayilov, Olgu Erkin Çınar, İbrahim C. Haznedaroğlu
doi: 10.4274/tjh.galenos.2023.2023.0288  Pages 59 - 60
Abstract |Full Text PDF

16. Ruxolitinib for the Treatment of Refractory Idiopathic Multicentric Castleman Disease: A Case Report
Yu-han Gao, Ming-hui Duan, Jian Li, Lu Zhang
doi: 10.4274/tjh.galenos.2024.2023.0477  Pages 61 - 63
Abstract |Full Text PDF

17. Rifampicin-Induced Toxic Hepatitis in a Patient with Hemophilia After Chemical Synovectomy
Mehmet Can Uğur, Semih Aydoğdu, Elçil Kaya Biçer, Can Balkan, Kaan Kavaklı
doi: 10.4274/tjh.galenos.2024.2023.0420  Pages 64 - 65
Abstract |Full Text PDF

18. Analysis of Hereditary FXII Deficiency Caused by Three Mutations Including a Novel Mutation
Longying Ye, Meina Liu, Lihong Yang, Mingshan Wang, Yaosheng Xie
doi: 10.4274/tjh.galenos.2024.2024.0016  Pages 66 - 68
Abstract |Full Text PDF