International Journal of Hematology-Oncology and Stem Cell Research

Hybrid Ganciclovir/Valacyclovir Prophylaxis Reduces CMV Reactivation in High-Risk Allogeneic Stem Cell Transplant Recipients

2025-10-21T12:47:06+0330

Background: Cytomegalovirus (CMV) reactivation remains a critical concern following allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in CMV-seropositive patients undergoing allo-HSCT from alternative donors. This study explored whether a hybrid CMV prophylaxis regimen would be more effective than the standard preemptive regimen in resource-limited settings where Letermovir is unavailable or cost-prohibitive.

Materials and Methods: This prospective single-center cohort study included adult patients with acute leukemia who received allo-HSCT from alternative donors between November 2018 and May 2022. The primary outcome was the evaluation of the CMV reactivation incidence in allo-HSCT patients receiving the hybrid CMV prophylaxis regimen comprising pretransplant ganciclovir followed by high-dose valacyclovir compared with the control patients who received the preemptive regimen. Secondary outcomes included overall survival (OS), disease-free survival (DFS), GVHD-free relapse-free survival (GRFS), and non-relapse mortality (NRM) between the two groups.

Results: A total of 80 patients, 34 received hybrid CMV prophylaxis, and 46 received the preemptive protocol. The hybrid prophylaxis group exhibited a significantly lower incidence of CMV reactivation at 90 days post-transplantation (34% vs. 82%, P = 0.000). However, no statistically significant differences were observed in overall survival, disease-free survival, or non-relapse mortality rates.

Conclusion: The hybrid regimen reduced CMV reactivation in high-risk HSCT recipients but did not improve survival outcomes, offering a practical alternative in settings with limited access to Letermovir.

Safety and Efficacy of Direct Oral Anticoagulants Compared to Warfarin in Patients with Venous Thromboembolism and Morbid Obesity

2025-10-21T12:47:10+0330

Introduction: Several guidelines recommend using direct oral anticoagulants (DOACs) over warfarin for the prevention of venous thromboembolism (VTE), except in cases of morbid obesity. The use of DAOCs in patients with morbid obesity has not been thoroughly evaluated due to the lack of representation in large clinical trials. To address this knowledge gap, we conducted a systematic review and meta-analysis of existing literature to determine the efficacy and safety of DOACs in patients with morbid obesity.

Materials and Methods: A systematic review of studies comparing DOACs with warfarin in patients with morbid obesity and diagnosed with acute VTE was conducted using electronic literature searches up to December 2021. Efficacy and safety were defined as the rate of recurrent VTE and major bleeding, respectively.

Results: A total of 30822 patients were included across 13 studies. Recurrent VTE events were observed in 713 of 12945 patients treated with DOACs, compared to 966 of 17877 patients treated with warfarin (OR, 0.70; 95% CI, 0.50-0.99; P=0.04; I²=69%). Major bleeding events occurred in 195 of 12675 patients on DOACs and in 386 of 17572 patients on warfarin (OR, 0.69; 95% CI, 0.58-0.82; P<0.0001; I²=0%). Similar findings were noted for two specific DOACS, apixaban and rivaroxaban, when evaluated individually against warfarin.

Conclusion: Our meta-analysis indicated that DOACs are both safe and effective in preventing VTE in patients with morbid obesity. DAOCs resulted in comparable outcomes to those observed with warfarin use. This analysis consolidates extensive observational data from a large patient cohort, thereby enhancing the evidence base for the use of DOACs in patients with morbid obesity.

Outcome of T-Lymphoblastic Leukemia-Lymphoma with Hyper C-VAD Regimen

2025-10-21T12:47:14+0330

Background: T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are aggressive diseases with dismal prognoses.

Materials and Methods: All adult patients with T-ALL and T-LBL who were candidates for the Hyper-CVAD chemotherapy protocol were included. We evaluated overall survival and progression-free survival in 46 new cases. The T-ALL and T-LBL’s number of cases were 32 and 14, respectively.

Results: Two- and 3-year OS were 41.8% (standard error (SE): 7%) and 27.8% (SE: 7%), respectively. Two- and 3-year PFS were 36.9% (SE: 7%) and 25.3% (SE: 7%), respectively. The only variable that had a significant relationship with the duration of PFS and OS was Allogenic SCT. Patients receiving Allogeneic SCT had longer survival time (2-year overall survival of 80% against 20%) (p˂0.001).

Conclusion: These data support the concept that Hyper-CVAD is not an appropriate and adequate regimen. We need new targeted agents in the T-ALL and T-LBL induction regimen while considering Allogeneic SCT as a Consolidation.

Expression of the FAM132B Gene in Iranian Patients with Beta-Thalassemia

2025-10-21T12:47:19+0330

Background: Iron homeostasis is a complex process involving multiple factors. Erythroblasts secrete erythroferrone (ERFE), which affects hepcidin production, thereby enhancing iron uptake. This study aimed to investigate the expression of the ERFE-encoding FAM132B gene in Iranian patients with beta-thalassemia major (BTM) and beta-thalassemia intermedia (BTI).

Materials and Methods: A total of 40 BTM and BTI patients and 20 healthy blood donors as a control group were recruited. Total RNA was extracted from whole blood samples, and cDNA was synthesized. Gene expression was quantified using a SYBR Green-based real-time PCR (RT-PCR) assay. Data analysis was performed by the GraphPad Prism program using the one-way ANOVA test.

Results: The expression of the FAM132B gene was upregulated in BTI patients compared to BTM patients (p = 0.0151). Despite the higher mRNA fold change in BTI patients, no significant difference was observed in the FAM132B gene expression between beta-thalassemia patients (major and intermedia) and the control group.

Conclusion: The expression of the FAM132B gene was different between beta-thalassemia major and intermedia patients. Further studies should be conducted to better elucidate the role of erythroferrone as a potential therapeutic target in patients with beta-thalassemia.

Apoptotic Events in Type-I Glanzmann Thrombasthenia Platelets

2025-10-21T12:47:22+0330

Background: Activated normal platelets undergo numerous biochemical and morphological changes, some of which are apoptotic. Phosphatidylserine (PS) expression, Δψm depolarization, microparticle (MP) formation, platelet shrinkage, release of cytochrome c, and caspase activation are hallmarks of both platelet activation and apoptosis. In this study, we report the apoptotic responses of type-I Glanzmann thrombasthenic platelets.

Materials and Methods: Platelets from twelve unrelated patients with type I Glanzmann thrombasthenia were examined as washed platelets. Calcium ionophore A23187 was used as an agonist to activate the platelets. Flow cytometry was employed to detect phosphatidylserine expression (Annexin A5 Alexa Fluor), Δψm depolarization (JC-10), platelet-derived MP formation (forward scatter; events <1.0 µm in size), and platelet shrinkage (mean-FSC). Anti-CD42b was used as a platelet-specific marker to distinguish platelets from other particles.

Results: We determined that increased cytosolic calcium significantly increased PS exposure, depolarized mitochondrial inner membrane potential (Δψm), increased microparticle formation, and induced platelet shrinkage in type-I Glanzmann thrombasthenic platelets. Our research showed that type I Glanzmann thrombasthenic platelets exhibit characteristics of platelet apoptosis. GPIIbIIIa deficiency does not limit platelet activation or apoptosis.

Conclusion: We conclude that GPIIb-IIIa-independent mechanisms may be involved in the normal apoptosis of thrombasthenic platelets. Our data deepen the understanding of the role of the platelet fibrinogen receptor in revealing aspects of normal apoptosis. However, this may help explain the normal platelet count among thrombasthenic patients.

Comparative Diagnostic Performance of Flow Cytometry, Aspiration, and Biopsy with Immunohistochemistry in Plasma Cell Neoplasms

2025-10-21T12:47:24+0330

Background: Plasma cell neoplasms (PCNs) are a heterogeneous group of hematologic malignancies that require accurate and timely diagnosis for effective management. Despite the availability of multiple diagnostic tools, challenges remain due to clinical and morphological variability. This study aimed to compare the diagnostic performance of three key modalities, including flow cytometry (FCM), bone marrow aspiration (BMA), and bone marrow biopsy with immunohistochemistry (BMB+IHC) in patients with plasma cell neoplasms.

Materials and Methods: A cross-sectional study was conducted on 52 patients with confirmed PCNs. Diagnostic outcomes from FCM, BMA, and BMB+IHC were evaluated and compared. Sensitivity, specificity, predictive values, and inter-method agreement were calculated using SPSS version 27.

Results: BMB+IHC achieved the highest diagnostic yield (100%), followed by BMA (55.8%), while FCM demonstrated the lowest diagnostic rate (32.7%). Flow cytometry showed excellent specificity and a positive predictive value of 100%, but limited sensitivity (32.7–58.6%), resulting in a high rate of false negatives. BMA frequently underestimated plasma cell burden due to sampling variability and hemodilution. Collectively, integration of all three methods provided complementary diagnostic value, reducing the risk of misclassification.

Conclusion: Bone marrow biopsy with immunohistochemistry remains the gold standard for diagnosing PCNs. However, combining it with aspiration and flow cytometry offers a more comprehensive diagnostic framework, improving accuracy, minimizing false negatives, and supporting optimal patient management.

Dysregulated Expression of miR-222 and miR-15a in Transfusion-Dependent Thalassemia: Associations with Torque Teno Virus and Cytomegalovirus Infections

2025-10-21T12:47:28+0330

Background: Beta-thalassemia is a hereditary blood disorder characterized by reduced synthesis of the beta-globin chain. MicroRNAs (miRs) are small RNA molecules that regulate gene expression and have been implicated in beta-thalassemia. To explore dysregulated miR-222 and miR-15a expression in transfusion-dependent beta-thalassemia and assess their potential associations with Torque Teno Virus and cytomegalovirus infections.

Materials and Methods: This study included 57 TDT patients registered at the Thalassemia Clinic affiliated with the Hematology Research Center, Shiraz, Iran. The expression levels of miR-222 and miR-15a were analyzed using the real-time SYBR Green PCR method. TTV and CMV infections were detected by analyzing the presence of their genomic DNA using an in-house semi-nested PCR protocol.

Results: The expression level of miR-222 was significantly up-regulated (47.5-fold, P≤0.001) in TDT patients compared to healthy controls. However, the expression of miR-15a in TDT patients was slightly decreased compared to healthy controls, but the difference was not statistically significant (P=0.193). TTV infection was observed in 21.1% of TDT patients, while CMV infection was detected in 5.2% of the patients. Although miR-222 and miR-15a gene expression levels were higher in TTV-positive patients compared to TTV-negative patients, the differences were not statistically significant (P=0.926 and P=0.243, respectively).

Conclusion: MiR-222 was up-regulated in TDT patients, but miR-15a did not show a significant difference. TTV and CMV infections were detected, but their association with miR expression was not significant, possibly due to the small sample size. Larger studies are needed for a more comprehensive evaluation.

The Interplay of Autoimmune Disease, Cancer, and Immunity: Current Understanding and Therapeutic Prospects

2025-10-21T12:47:31+0330

Background: In light of chronic inflammation and dysregulated immune responses, autoimmune disorders and cancer are closely related. It is essential to comprehend how they interact in order to create immunotherapeutic techniques that work.

Materials and Methods: The purpose of this review is to summarize the most recent research on the relationship between immunology, cancer, and autoimmune illnesses and to assess new treatment strategies that target each of these diseases. PubMed, MEDLINE, the Cochrane Library, Embase, and Scopus were used in a methodical search (2010–2023). Studies evaluating immunotherapy results, immunological processes, and cancer incidence in patients with autoimmune diseases were all eligible. Using random-effects meta-analysis, the data were examined.

Results: A total of 78,456 patients from fifty-seven studies were examined. Patients with autoimmune diseases had a considerably higher risk of developing cancer (OR = 1.58; 95% CI: 1.42–1.76; p < 0.001), frequently as a result of immunosuppressive treatment and persistent inflammation. Among the common mechanisms were increased pro-inflammatory cytokines (TNF-α, IL-6) and dysregulation of immunological checkpoints (PD-1/PD-L1). Although cytokine blockers and checkpoint inhibitors have demonstrated effectiveness, they also carry significant hazards.

Conclusion: The confluence of immune regulation, cancer, and autoimmunity brings to light both treatment possibilities and difficulties. Future studies should concentrate on tailoring immunotherapies to optimize their positive effects while reducing their negative ones.

Narrative Review of Advancements in Stem Cell Therapy: Adipose-Derived Stem Cells for Diabetic Foot Ulcer Treatment

2025-10-21T12:47:37+0330

Diabetic foot ulcers (DFUs) are a severe complication of diabetes, with current standard care often failing to prevent chronic morbidity and amputation. This narrative review examines the therapeutic potential of adipose-derived stem cells (ADSCs) for DFUs treatment. ADSCs promote healing through paracrine secretion of growth factors, immunomodulation, and stimulation of angiogenesis, as demonstrated in promising preclinical and early clinical studies. We outline these mechanisms, discuss the emerging role of ADSC-derived exosomes as a potentially safer alternative, and summarize key clinical findings. However, significant challenges remain, including potential risks of tumorigenicity, donor cell variability, and a lack of standardized protocols. While ADSC therapy represents a highly promising regenerative approach for DFUs, its safety and efficacy must be firmly established through more rigorous preclinical studies and large-scale, randomized controlled trials before it can be broadly adopted in clinical practice. This review concludes that while ADSC therapy is a highly promising regenerative approach for DFUs, its translation to clinical practice necessitates further rigorous investigations to overcome existing translational barriers.

Genetic Engineering in Hematopoietic Stem Cells for β-Hemoglobinopathies Treatment: Advances, Challenges, and Clinical Translation

2025-10-21T12:47:40+0330

β-hemoglobinopathies rank among the most prevalent inherited blood disorders globally. Traditional management strategies are primarily palliative and often associated with significant challenges, including iron overload and limited long-term efficacy. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for transfusion-dependent patients, but its broader applicability is constrained by factors that limit its use. Utilizing viral vectors and gene-editing tools, particularly CRISPR-Cas9 technology, researchers have developed therapies that target the root causes of these disorders. These innovative approaches have demonstrated substantial therapeutic potential, accompanied by favorable safety profiles, in clinical settings. Since the initial investigations, the genome editing tool has rapidly advanced for genetic abnormalities, particularly monogenic blood diseases, including β-hemoglobinopathies. This method suggests an approach with lower concerns in viral gene integration and insertional mutagenesis issues. This review comprehensively surveys the therapeutic strategies for β-thalassemia and sickle cell disease (SCD) currently in preclinical and clinical development, with a focus on the evolving treatment paradigm. Looking forward, critical research priorities include optimizing the efficiency and specificity of gene-editing platforms and pioneering novel delivery systems to guarantee both therapeutic efficacy and clinical safety.

Report of Granular Blasts in Adult B-Cell ALL: A Rare Morphological Mimic of AML

2025-10-21T12:47:43+0330

Granular ALL is one of the uncommon morphological variants of acute lymphoblastic leukemia (ALL), characterized by cytoplasmic granules in lymphoid blasts. This rare morphological presentation may lead to diagnostic misinterpretation. Case reports of such presentations enhance understanding of disease biology and therapeutic considerations.

Case presentation: A 22-year-old woman with Granular ALL has been discussed here. In the Peripheral blood smear (PBS) of this patient, cytoplasmic granules were identified in the cytoplasm of lymphoblasts. Further examinations were conducted on the bone marrow aspiration (BMA) sample of the patient, including karyotyping, flowcytometric and conventional molecular evaluations for ALL. The flow cytometric results were consistent with a diagnosis of B-ALL; the karyotyping analysis showed 47, XX, +17[4], and molecular findings revealed no detectable abnormalities.

Conclusion: Due to the misdiagnosis of Granular ALL as AML, the identification of distinguishing diagnostic features of Granular ALL is clinically significant. In this context, flow cytometric, cytogenetic, and molecular findings are invaluable to distinguish between these two types of acute leukemia.

Ulcerated Tongue Borders as a Sign of Amyloidosis in a Patient with Multiple Myeloma

2025-10-21T12:47:47+0330

Amyloidosis is characterized by extracellular deposition of amyloid material in various tissues and organs. Deposition of amyloid in the tongue is rare but often occurs in multiple myeloma. Here we present the case of a 44-year-old woman under treatment for multiple myeloma who complained of lateral tongue pain. Intraoral examination revealed an ill-defined, firm, whitish swelling with an ulcerated surface on the bilateral borders of the tongue. Histopathological analysis revealed a lympho-mononuclear infiltration in the lamina propria with the presence of acellular and amorphous material positive for Congo red staining. Further examination revealed amyloidosis in a cervical mass associated with neural compression. Thorough examination of the oral cavity in patients with multiple myeloma is critical for early detection of amyloidosis. A biopsy is mandatory to confirm the diagnosis, thereby facilitating intervention and management if necessary.