
Background: Multiple myeloma is a heterogeneous malignancy with patchy bone marrow involvement, often leading to discrepancies between biochemical and imaging-based response assessments. Site-specific bone marrow biopsies may miss focal disease, while FDG PET/CT detects metabolically active lesions, offering complementary prognostic value. Materials and Methods: This prospective study included 44 newly diagnosed multiple myeloma patients. The primary aim was to assess the correlation between biochemical and PET/CT responses at six months post-induction. A secondary objective was to evaluate the impact of PET/CT response on 12-month EFS. Results: The median age was 55.5 years. At baseline, >3 focal lesions and EMD were observed in 61.4% and 34.1% of patients, respectively. After six months of induction therapy, 86.3% achieved ≥VGPR biochemically, but 52.3% remained PET/CT-positive. Baseline >3 focal lesions and extramedullary disease (EMD) significantly predicted persistent PET/CT positivity (p = 0.004). Notably, 50% of patients with ≥VGPR (very good partial response) still showed PET/CT-positive findings. At 12 months, 75% of patients with clinical events had positive PET/CT at six months versus 47.2% without events (p = 0.245). Event-free survival was lower in the PET/CT-positive group (73.9% vs. 90.4%, p = 0.182), though not statistically significant. Conclusion: 18-FDG PET/CT can detect residual disease not captured by biochemical markers, highlighting the value of combined assessment in multiple myeloma. Baseline >3 focal lesions and EMD predicted persistent PET/CT positivity. Although PET/CT positivity at six months showed a trend toward worse 12-month EFS, larger studies are needed to confirm its prognostic significance.
Background: Cervical cancer is a major public health issue, particularly in low- and middle-income countries. Early detection through effective screening methods is crucial for reducing morbidity and mortality. Opportunistic cervical cytology testing in outpatient settings plays an important role in the early identification of precancerous lesions. Materials and Methods: This cross-sectional study aimed to evaluate the effectiveness of LBC in detecting precancerous lesions and cervical cancer in a defined population. One hundred women aged between 25 and 75 were screened using LBC. Cytological specimens were processed and analyzed by experienced cytopathologists. Results: The primary outcome measures were the detection rate of precancerous lesions and cervical cancer, and the identification of factors associated with an increased risk of developing cervical cancer. Most of the patients who attended the OPD were in the fourth decade of life (37 cases, 37%), followed by 23 patients (23%) in the third decade. About 72.7% of patients who were diagnosed with LSIL and HSIL were in the age group of 51–70 years. Out of 100 patients, 13 had premalignant lesions and 2 had carcinoma. Conclusion: The results of this study will provide valuable insights into the performance of LBC in a specific population setting. This information can contribute to the development and implementation of effective cervical cancer screening programs and ultimately reduce the burden of this disease.
Invasive fungal infections are a leading cause of death in patients with hematological malignancies and those receiving bone marrow transplants. Although standard guidelines exist globally, their direct application in Iran is not always possible due to differences in the types of common fungi and limited diagnostic and therapeutic facilities. To address this challenge, a national committee of experts in the field was formed to carefully review internationally recognized protocols published up to 2024 and solicit opinions from selected experts across the country to develop the first national guideline specifically for prophylaxis. To ensure methodological rigor, the Appraisal of Guidelines for Research and Evaluation II (AGREE II) framework and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were utilized. The resulting consensus established a localized risk-stratification model identifying acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and active graft-versus-host disease (GVHD) patients as high-risk, recommending posaconazole as the primary standard. Notably, the guideline advises against routine azole use in acute lymphoblastic leukemia (ALL) to prevent neurotoxicity. Furthermore, a resource-tiered framework was developed for centers with varying diagnostic capabilities. The result of this effort was to present a tiered and local model that provides a practical solution for both well-equipped and limited facilities. The existence of this national guideline creates a major advantage in that treatment approaches are unified and standardized across the country. By eliminating discretionary decisions, this document helps to better manage medication use and ultimately improve patient outcomes, regardless of the city in which they are treated or the facilities they are treated at.
Background: The Rh blood group system is highly significant in transfusion medicine because of the strong immunogenicity of the D antigen. The RhD-negative phenotype arises through various molecular mechanisms in different populations, most commonly complete deletion of the RHD gene caused by unequal recombination between upstream and downstream Rhesus box sequences. Although this mechanism has been well documented in some populations, limited data are available from Iran, particularly its eastern regions. This study aimed to determine the molecular basis of the RhD-negative phenotype among blood donors in eastern Iran. Materials and Methods: In this cross-sectional study, a total of 16,190 blood donors referred to blood transfusion centers in South Khorasan Province, eastern Iran, over a one-year period were screened serologically for RhD status. Among them, 2,198 individuals were identified as RhD-negative, and 100 serologically confirmed RhD-negative donors were randomly selected for molecular evaluation. RhD typing was performed using standard serologic methods and verified by indirect antiglobulin testing. Molecular investigations included PCR-SSP targeting RHD exons 5, 7, and 10, real-time PCR for confirmation, and PCR-RFLP to detect the hybrid Rhesus box and determine RHD zygosity. Results: Among 16,190 blood donors screened during the study period, 2,198 (13.57%) were identified as RhD‑negative. From this group, 100 samples were randomly selected for molecular analysis. Both PCR‑SSP and real‑time PCR demonstrated the absence of RHD exons 5, 7, and 10 in all samples, indicating complete deletion of the RHD gene. PCR‑RFLP analysis further showed that all donors were homozygous for the hybrid Rhesus box, with full concordance observed between exon‑specific assays and hybrid Rhesus box genotyping. Conclusion: These findings indicate that the RhD-negative phenotype is primarily due to homozygous RHD gene deletion mediated by the hybrid Rhesus box. Hybrid Rhesus box analysis may therefore serve as a reliable molecular marker for accurate RhD typing, improving transfusion safety and perinatal management.
Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs that control protein-coding gene expression, and alterations in their expression are associated with leukemic changes in hematopoietic cells. The current study was performed on bone marrow samples from Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph−) ALL patients to assess miR-320a and miR-206, as well as their relationship with the prognosis of ALL. Materials and Methods: miR-206 and miR-320a expression levels were assessed using Real-Time PCR in 50 bone marrow specimens from 10 healthy individuals (as a control group), 20 Ph+ ALL patients, and 20 Ph- ALL patients. The data were analyzed using GraphPad Prism version 7, one-way ANOVA, and Chi-square tests. Results: The present study reports on the differential expression of miR-206 in Ph- and Ph+ ALL groups in comparison to normal individuals. The Ph- ALL group exhibited a significant 3.8-fold reduction in expression (P = 0.004), while the Ph+ ALL group demonstrated a noteworthy 5.34-fold increase in expression (P = 0.006) relative to the control group, although no statistically significant differences were observed in the comparison of miR-320a expression between Ph+ and Ph- patients (P = 0.496 and P = 0.645, respectively). Data analysis showed no relationship between age, sex, and miRNA expression. Conclusion: MiR-206 showed a different expression pattern, and it seems that this miRNA was upregulated in Ph+ ALL and downregulated in Ph- ALL patients, and may serve as a potential prognostic and diagnostic biomarker for distinguishing between the two ALL groups.
Patients with acute leukemia are immunocompromised and highly susceptible to infections. Central nervous system tuberculoma is a rare but serious complication in immunocompromised patients, particularly those undergoing treatment for hematological malignancies. Early diagnosis is often challenging due to non-specific symptoms. We report the case of a 28-year-old female recently diagnosed with CALLA-positive B-cell Acute Lymphoblastic Leukemia, who presented with a two-month history of low-grade fever. Induction chemotherapy was initiated, but during the third week of treatment, she developed new-onset seizures. A Computed Tomography scan of the brain revealed a heterogeneous ring-enhancing lesion in the right parietal lobe. Magnetic Resonance Imaging with MR spectroscopy demonstrated characteristic lipid peaks, supporting the diagnosis of a tuberculoma. Antitubercular therapy including rifampicin, isoniazid, pyrazinamide, ethambutol, along with pyridoxine and dexamethasone, was commenced. The patient showed a favourable response, with resolution of fever and no recurrence of seizures. This case underscores the importance of considering CNS tuberculosis in the differential diagnosis of unexplained neurological symptoms and fever in patients with acute leukemia, particularly in regions where tuberculosis is endemic. Prompt diagnosis and treatment can lead to favourable outcomes.
DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe toxicoderma characterized by a hypersensitivity reaction to medications, accompanied by eosinophilia and systemic manifestations. Apalutamide, a selective androgen receptor inhibitor approved for the treatment of prostate cancer, has been associated with various dermatological complications. This study aims to document the clinical case of a geriatric patient with stage IV prostate cancer who developed toxicoderma after initiating treatment with apalutamide. An 81-year-old patient with a diagnosis of stage IV acinar adenocarcinoma of the prostate presented with a 15-day history of generalized papular lesions and general malaise, without improvement despite the use of oral antihistamines. The patient reported having started apalutamide four weeks prior. Physical examination revealed facial edema and erythema, with erythematous and edematous plaques with a desquamative surface covering more than 50% of the body surface. Laboratory results showed eosinophils at 3040 cells/µL and a rise in baseline creatinine from 1.76 mg/dL to 2.4 mg/dL. The RegiSCAR score was 3 points, classifying it as a possible case of DRESS. A skin biopsy revealed a dermoepidermal hypersensitivity reaction with eosinophilic infiltration. The patient improved with oral and topical corticosteroids and the discontinuation of apalutamide. The diagnosis of DRESS was confirmed, and the patient remains under follow-up by the Oncology service.Several medications have been associated with the development of DRESS syndrome. Early recognition allows for the suspension of the causative treatment, thus reducing patient morbidity and mortality. It also facilitates a timely change in oncological therapy in advanced stages, preventing the patient from being left without adequate cancer management.
Background: This study aimed to analyze the effect of a single injection of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) at a dose of 1 × 10⁶ cells/kg on insulin levels and weight gain in physiologically aging female rats. Materials and Methods: This study used a group of female rats (12 rats) divided into three groups: Group A (three-month-old young female rats with no treatment as control), Group B (24-month-old aging female rats injected with 0.9% NaCl in 0.4 mL as control), and Group C (24-month-old aging female rats injected with hWJ-MSCs at a dose of 1 × 10⁶ cells/kg in 0.4 mL as treatment). The injections were administered four times at three-month intervals. At the end of this experiment (12 months), the rats were anesthetized and sacrificed. Insulin levels were measured using ELISA. Immunohistochemical staining was performed to detect the homing of hWJ-MSCs in pancreatic tissue. Results: The data showed that rats treated with hWJ-MSCs had lower weight compared with the control group. Insulin hormone levels in treated aging rats were significantly different from those in the aging control group. Immunohistochemical results showed that hWJ-MSCs were widely distributed in the islets of Langerhans of treated aging rats. Conclusion: The results of this study indicate that body weight and insulin levels in physiologically aging female rats change with age. Wharton's jelly mesenchymal stem cells injected intravenously four times at a dose of 1 × 10⁶ cells/kg in physiologically aging female rats successfully migrated and homed to the islets of Langerhans, showed a trend toward reduced weight gain, and significantly increased insulin levels.
Background: Acute myeloid leukemia (AML) is a heterogeneous disease with diverse genetic alterations influencing prognosis and treatment outcomes. Isocitrate dehydrogenase (IDH) genes, particularly IDH1 and IDH2, have emerged as important biomarkers, but the prognostic impact of their mutations remains controversial. This systematic review and meta-analysis aimed to evaluate the prognostic significance of IDH mutations in AML, focusing on overall survival (OS) and relapse-free survival (RFS). Materials and Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science to identify eligible studies published up to February 2025. Studies reporting the association between IDH mutations (IDH1 and IDH2) and survival outcomes in AML were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted or derived when necessary. Results: The analysis included 33 studies (n= 17,576). IDH2 mutations were associated with improved overall survival (HR = 0.70, 95% CI: 0.63–0.78) and relapse-free survival (HR = 0.65, 95% CI: 0.52–0.82), particularly in patients treated with IDH inhibitors. IDH1 mutations were linked to poor outcomes (OS HR = 1.16, 95% CI: 1.07–1.25; RFS HR = 1.03, 95% CI: 0.76–1.41). Subgroup analysis showed a more favorable prognosis for IDH2 R140 mutations, whereas IDH2 R172 mutations demonstrated heterogeneous outcomes across studies and treatment settings. Conclusion: IDH mutations have a significant but heterogeneous prognostic impact in AML, with IDH2 mutations generally associated with better outcomes compared to IDH1 mutations. Larger, well-designed studies with comprehensive molecular profiling are needed to clarify the prognostic implications of IDH mutations in AML.
Background: Anemia is a common clinical condition in hematology, associated with diverse etiologies and treatment strategies, many of which have notable limitations. Luspatercept, a novel erythroid maturation agent, has shown promise in treating anemia, particularly in patients with β-thalassemia and myelodysplastic syndromes (MDS). This study aimed to evaluate the real-world hematologic effectiveness of luspatercept across various anemia subtypes. Materials and Methods: A retrospective observational study was conducted on 22 patients with anemia of different origins—MDS, post-hematopoietic stem cell transplantation (HSCT), aplastic anemia (AA), and T-cell large granular lymphocytic leukemia (T-LGLL)—who received luspatercept therapy at the 960th Hospital from June 2023 to January 2025. Hematologic improvement was assessed using the International Working Group (IWG) 2018 criteria for erythroid response (HI-E). Pre- and post-treatment changes in hemoglobin (Hb), reticulocyte percentage (RET %), and absolute reticulocyte count (RET #) were analyzed using the Wilcoxon Signed-Rank Test. Multivariate regression was employed to control for age, gender, and disease severity. Statistical significance was set at P ≤ 0.05, and all analyses were performed using SPSS version 27.0. Results: Among the 22 patients, 10 (45.5%) had MDS (5 low-risk, 5 intermediate-to-high-risk), 6 (27.3%) post-HSCT anemia, 4 (18.2%) AA, and 2 (9%) T-LGLL. A total of 16 patients (72.7%) achieved a clinically meaningful erythroid response. Seven (43.8%) of these remained transfusion-independent until the last follow-up, with a median duration of 19.5 weeks (range: 8.6–47). Median time to initial response was 3.86 weeks (range: 0.57–25.57). Significant increases were observed in Hb (P < 0.001) and RET # (P = 0.001), while the increase in RET % did not reach statistical significance (P = 0.088). These findings support the efficacy of luspatercept in promoting erythropoiesis and improving anemia in a heterogeneous patient population. Conclusion: Luspatercept demonstrated significant hematologic improvement, particularly in hemoglobin levels, in patients with anemia from various hematologic disorders. These results support its broader therapeutic potential. Future multicenter, prospective studies are warranted to validate its role in treating other forms of anemia.
Three-dimensional convolutional neural networks (3D CNNs) have transformed oncology imaging by offering superior performance in tumor detection, classification, segmentation, and prognosis prediction. Unlike traditional two-dimensional CNNs, 3D CNNs can effectively analyze volumetric medical imaging data, improving spatial feature extraction and diagnostic accuracy across imaging modalities such as CT, MRI, PET, and ultrasound. This systematic review and meta-analysis evaluates the diagnostic capabilities and clinical utility of 3D CNNs across 22 studies, including 11 eligible for quantitative synthesis. The pooled sensitivity, specificity, and AUC-ROC were 0.72, 0.73, and 0.77 respectively, with a diagnostic odds ratio (DOR) of 10.38, indicating favorable discriminative performance. Subgroup analyses revealed superior accuracy in lung cancer and CT-based models, with DenseNet and ResNet architectures outperforming traditional CNNs. Technical innovations including multi-modal fusion, spatial context integration, and explainable AI techniques enhance model robustness and clinical trust. However, high heterogeneity (I² > 95%) across studies, attributable to variations in imaging protocols, dataset quality, and model design, underscores the need for standardized methodologies. Limitations such as computational demands, annotation variability, and generalization challenges persist. Future directions emphasize the integration of explainable AI, PACS-compatible user interfaces, and federated learning frameworks to bridge institutional gaps. This review highlights the significant potential of 3D CNNs in advancing precision oncology, while also identifying the infrastructural and methodological refinements needed to enable widespread clinical adoption.
Oral lichen planus (OLP) is a chronic, T-cell-mediated inflammatory disease of the oral mucosa, notable for its symptomatic burden and potential for malignant transformation. While corticosteroids and immunosuppressants remain the standard of care, their transient efficacy and adverse effect profile underscore a significant unmet clinical need. Mesenchymal stem cells (MSCs), with their multifaceted immunomodulatory and regenerative capabilities, are emerging as a compelling therapeutic alternative. This editorial synthesizes current evidence, positing that MSCs can fundamentally disrupt the immunopathogenic cycle of OLP. We explore the mechanisms by which MSCs re-establish immune tolerance and promote tissue repair, and we critically assess the translational pathway from preclinical models to clinical application. Despite promising results, the journey to clinical adoption necessitates overcoming hurdles in standardization, delivery, and safety profiling. We argue that MSC-based therapy represents not merely an incremental improvement, but a potential paradigm shift towards a curative strategy for this recalcitrant disease.
Paraneoplastic pemphigus (PNP) is a rare, severe autoimmune mucocutaneous disorder most commonly associated with lymphoproliferative malignancies. Here, we report the first documented case of PNP as a paraneoplastic manifestation of multiple myeloma (MM). A 61-year-old male with MM developed widespread mucocutaneous ulcerations shortly after his eleventh chemotherapy cycle, initially suspected to represent Stevens-Johnson syndrome. Clinical examination revealed diffuse skin peeling, mucosal involvement of the eyes, oral cavity, and genital region, and a positive Nikolsky sign. Laboratory evaluation demonstrated acute kidney injury requiring hemodialysis. Despite initial treatment with high-dose intravenous immunoglobulin, lesions persisted. Skin biopsy revealed lichenoid lymphocytic infiltration, basal vacuolar changes, subcorneal and suprabasal acantholysis, and keratinocyte dyskeratosis, confirming PNP. Viral serologies were negative, supporting the autoimmune etiology. The patient was subsequently treated with rituximab, resulting in significant improvement of cutaneous lesions over three months, with residual post-inflammatory hyperpigmentation. This case emphasizes the importance of early recognition and accurate differentiation of PNP from other blistering disorders in patients with underlying hematologic malignancies. Importantly, this represents the first reported instance of PNP presenting as a paraneoplastic manifestation of MM, highlighting the need for awareness of atypical autoimmune syndromes in this population.
Hepatocellular carcinoma (HCC) is a crucial health concern worldwide, representing a leading cause of cancer-related mortality and the most common form of primary liver cancer. The aggressive nature of HCC is mainly due to its high tendency for invasion and metastasis, processes regulated by a complex network of genetic and molecular pathways. Among the critical regulators of these processes is microRNA-21 (miR-21), a small non-coding RNA that implicated in various oncogenic activities. This review provides a comprehensive analysis of the role of miR-21 in promoting HCC metastasis, with a particular focus on its interaction with key signaling pathways, including the PTEN/PI3K/AKT, PDCD4/AP-1, RECK/MMP, and TIMP-3 axes. By targeting tumor suppressors, miR-21 facilitates epithelial-to-mesenchymal transition (EMT), invasion, and metastasis of HCC cells. Understanding the molecular mechanisms regulated by miR-21 not only sheds light on the pathogenesis of HCC but also highlights potential therapeutic targets for combating this aggressive cancer.
Supradiaphragmatic lymphadenopathy is a rare finding in prostate cancer. The occurrence of multiple lymphadenopathies forming a conglomerate that resembles lymphoma is also rarely encountered in prostate cancer diagnosis. We present the case of a 71-year-old man who has experienced bilateral leg swelling in the last four months. Multiple lymphadenopathies were detected in the intra-abdominal and supradiaphragmatic regions, along with several metastatic bone lesions. Histopathological and immunohistochemical evaluations confirmed a diagnosis of prostate adenocarcinoma, not otherwise specified (NOS), with a Gleason score of 4+3=7, classified as grade group III, indicating high-volume metastatic prostate cancer. The patient was treated with docetaxel and anti-androgen therapy. His condition improved after eight cycles of chemotherapy, and his prostate-specific antigen (PSA) levels returned to normal.
Rhabdomyosarcoma (RMS) is a primitive mesenchymal malignancy of childhood and is very rare in adults. In the presence of a soft tissue mass, bone marrow metastasis of RMS is easy to diagnose. However, RMS can rarely present with extensive marrow replacement, without an obvious primary-a situation that is very challenging for the pathologist as well as the clinician. Owing to the classical round cell morphology, metastatic RMS is morphologically indistinguishable from acute leukemia, especially when the cells are singly scattered, rather than in clusters. We report a rare presentation of bone marrow metastasis of embryonal RMS in an adult, who presented only with pancytopenia and leucoerythroblastic blood picture. Bone marrow aspiration revealed near-total replacement of the hematopoietic elements by atypical blast-like cells, which were singly scattered as well as arranged in loose clusters focally. The case was worked up as acute leukemia. Flow cytometric immunophenotyping ruled out acute leukemia. The trephine biopsy was more in favor of a metastatic tumor; hence, a PET-CT was performed. The scan revealed diffuse uptake in the axial and appendicular skeleton, along with enlarged supraclavicular lymph nodes. An excision biopsy of the lymph node clinched the diagnosis of metastatic RMS, which was confirmed by immunohistochemistry for desmin and Myo-D1. This report highlights a rare case of adult embryonal RMS and emphasizes the importance of a multidisciplinary diagnostic approach for metastatic disease in this population.
This case report describes the presentation for a 65-year-old patient with Sweet's syndrome (SS) presenting with systemic symptoms of general weakness, fever, and painful skin lesions on the right arm. He reported a history of weight loss with night sweats, while skin lesions manifested as erythematous plaques and painful papules. The diagnosis was confirmed by skin biopsy, which showed features of significant neutrophilic infiltration on histopathology. Further investigations led to the diagnosis of AML associated with Sweet's syndrome. The study highlights the importance of prompt diagnosis of Sweet's syndrome as a paraneoplastic sign and of using multidisciplinary approach for diagnosis and management of patients with skin lesions and cytopenias.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe hyperinflammatory syndrome caused by uncontrolled activation of macrophages and cytotoxic T cells. It is frequently underdiagnosed, leading to significant morbidity and mortality in pediatric populations. Early identification and treatment are critical to improving prognosis. Materials and Methods: This retrospective study analyzed demographic, clinical, and laboratory data of pediatric patients aged 0 to 18 years diagnosed with HLH according to the HLH-2004 criteria. Patients admitted to our center between February 2021 and February 2023 were included. We aimed to describe common presenting symptoms, laboratory abnormalities, treatment modalities, and patient outcomes. Results: A total of 35 children diagnosed with HLH were included; 51% were female. The mean age was 6.1 years, with an age range from birth to 18 years. Fever was the most frequent presenting symptom, reported in 85% of cases. Hemophagocytosis in bone marrow aspirates was detected in 41% of patients. The overall mortality rate was 11%. Notably, 20% of patients tested positive for anti-COVID-19 IgG antibodies, suggesting a possible temporal association with the development of HLH. Comparative analysis indicated that deceased patients had significantly lower fibrinogen levels (p = 0.04) and higher triglyceride levels (p = 0.03). Treatment regimens varied according to clinical presentation and severity. Conclusion: HLH remains a challenging diagnosis due to its variable presentation and potential to rapidly progress to life-threatening immune activation. Prompt recognition and timely initiation of appropriate therapy are vital for improving outcomes in affected children. Increased awareness among clinicians and early intervention can reduce morbidity and mortality associated with this condition.
Background: Acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) are rare blood cancers with poorer survival in adolescents and young adults (AYAs) than in children. Pediatric-inspired regimens like CALGB 10403 have improved outcomes in AYAs. This study evaluated the effectiveness, feasibility, and treatment-related toxicities of CALGB 10403 in AYAs with ALL/LBL treated at Seyed Al-Shohada Hospital, Isfahan, Iran, from December 2021 to May 2024 Materials and Methods: AYAs aged 17-39 with newly diagnosed ALL/LBL (excluding Burkitt, Ph+, and prior treatment) were included. Baseline characteristics and outcomes of interest (induction response, event-free and overall survivals) were collected. Induction response was assessed via bone marrow (ALL) or CT scan/biopsy (LBL). Minimal residual disease (MRD) was evaluated by flow cytometry. Treatment-related toxicities were monitored and graded per CTCAE criteria. The feasibility of implementing the CALGB 10403 protocol was evaluated by measuring treatment delays. Results: Seventeen AYA patients with newly diagnosed ALL/LBL (median age 21) were enrolled, mostly male (14/17). Fourteen had ALL, and three had LBL. Extramedullary involvement was seen in 29%, including lymphadenopathy, bulky mediastinal masses, and CNS involvement. Sixteen patients (94%) achieved remission, with no deaths during the induction course. One-year EFS and OS were 77% and 100%, respectively. Common toxicities included hyperbilirubinemia, elevated transaminases, and infections. Treatment delays, mainly from non-adherence, occurred in 53%. Eight patients achieved MRD negativity after Course I. Conclusion: This study provides insights into the first Iranian experience with the CALGB 10403 protocol for AYAs with ALL/LBL, a regimen that has demonstrated encouraging survival outcomes in U.S. trials.