Search Results (111)

Background: Higher-risk myelodysplastic syndromes (HR-MDS) carry a high risk of progression to acute myeloid leukemia and poor overall survival. Hypomethylating agents (HMAs), such as azacitidine, remain the standard of care but have limited efficacy. A 15-day venetoclax-azacitidine regimen has shown promising objective response rates (ORR) and potential as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in relapsed/refractory HR-MDS. We conducted a prospective multicenter trial to evaluate its efficacy and safety in previously untreated patients. Methods: This multicenter prospective study enrolled treatment-naïve HR-MDS patients (IPSS-R > 3.5). Venetoclax was administered on days 1–15 (escalated from 100 to 400 mg), combined with azacitidine (75 mg/m²) on days 1–7 of each 28-day cycle. The primary endpoint was ORR (2006 IWG criteria); secondary endpoints included complete remission (CR), overall survival (OS), and AML progression. Results: Twenty-eight patients (median age: 63 years) were enrolled, with a median follow-up of 8.5 months. ORR was 85.7% per 2006 IWG (CR: 35.7%, marrow CR: 50.0%), and 78.6% per 2023 IWG (CR: 35.7%). Responses were consistent across molecular and IPSS-R subgroups. Median OS was not reached. High neutrophil count and high cytogenetic risk were favorable factors; TP53 mutation/deletion was an adverse prognostic marker. Grade 3–4 hematologic toxicities included neutropenia (96.4%), anemia (71.4%), and thrombocytopenia (64.3%). Serious adverse events (35.7%) were mainly infections. No dose-limiting or unexpected toxicities were observed. Conclusions: The 15-day venetoclax plus azacitidine regimen demonstrated high efficacy and manageable toxicity in treatment-naïve HR-MDS. It may be particularly beneficial for patients with high neutrophil counts, adverse cytogenetics, or those eligible for HSCT, supporting further investigation in larger trials. Full article

Background and Clinical Significance: Histiocytic sarcoma (HS) is a rare and aggressive form of malignant histiocytosis, often associated with poor prognosis. The diagnosis and management of HS are challenging due to the complexity of its pathogenesis, molecular profile, and the unclear cellular origin of histiocytic neoplasms, compounded by the limited literature on treatment strategies. Case Presentation: We report the case of a young patient with HS localized to the lymph nodes, spleen, and liver, who also presented with hemophagocytic lymphohistiocytosis (HLH) documented on bone marrow biopsy. Initial treatment with CHOEP-21 and ICE-21 chemotherapy resulted in only a partial metabolic response, as evidenced by a Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET)/CT scan. Given the aggressive nature of the disease and the presence of HLH, an allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was performed as consolidation therapy, leading to a progressive complete response without significant toxicity. A suspected relapse at 18 months post-transplant was excluded following a mediastinal lymph node biopsy, which revealed a benign intravascular papillary endothelial hyperplasia (IPEH). Over five years post-diagnosis and more than four years after transplantation, the patient remains in complete remission with full functional recovery. Conclusions: This case highlights the diagnostic and molecular challenges of HS and demonstrates the curative potential of early allogeneic HSCT, even when only partial remission is initially achieved. Full article

Background: Endometrial cancer (EC) is a common malignancy found among women. It is ranked as the 6th most common cancer among women and the 15th most common cancer globally. Increasing prevalence of several factors like obesity and other metabolic disorders have caused a growing trend of prevalence of endometrial cancer. The standard approach of treatment with excellent prognosis is total hysterectomy with bilateral salpingo-oophorectomy (TH/BSO). However, due to its drawback of complete infertility, newer approaches of fertility-sparing approaches are emerging to combat this challenge. Clinicians must choose the most suitable candidates for fertility-sparing surgery (FSS) using the present existing conventional criteria with regard to the patient’s age, tumor characteristics, and fertility goals. The limitations using the conventional criteria can be eliminated by refining the criteria with molecular prognostic factors to ease the candidate selection process for FSS. Methods: Relevant literature regarding molecular subtypes, hormone therapy sensitivity, clinical assessment, and guidelines pertaining to fertility preservation in EC were retrieved from several electronic databases and articles addressing the role of molecular profiling in predicting patient response, guiding patient selection, and/or informing the development of therapies for fertility preservation in early-stage EC, particularly in women of reproductive age were included. Primary focus was on areas of consensus, emerging trends, and evidence gaps that warrant further investigation. This review will assess the integration of molecular prognostic factors to refine the patient selection criteria and guide FSS in early-stage EC. We will present existing clinical criteria, ongoing clinical trials, limitations, and the advantages of integrating molecular data on patient selection, treatment safety, and fertility outcomes. Results: Four distinct molecular subtypes have been classified which includes POLE-mut, MMR-d, p53-abn and NSMP. POLE-mut subtype had excellent prognosis with >95% patients achieving complete remission with <2% recurrence rate followed by MMRd and NSMP with intermediate prognosis and lastly p53-abn with poor prognosis of 60–70% achieving complete remission and 30–40% having recurrence. The data highlights the clinical value of molecular classification in selecting appropriate candidates for fertility sparing surgery (FSS). Conclusions: There is a lack of integration of molecular subtypes for clinicians to choose candidates for FSS and this gap should be addressed. Further research must be performed to follow personalized medicine to refine their treatment plan. Full article

Background and Objectives: The biological behavior of gliomas is influenced by various factors including molecular features and treatment response. This study investigates the prognostic implications of a second tumor in patients with glioma at time of diagnosis. Given the increasing number of patients presenting with multiple primary malignancies due to improved cancer survival and diagnostic accuracy, understanding the influence of double tumor burden on glioma outcomes is of growing clinical relevance. Methods: We retrospectively analyzed adult patients with intracranial gliomas (WHO grade 2–4), who were surgically treated between 2015 and 2022 at our institution. Patients were categorized into two groups: glioma only and glioma plus additional solid malignancy. We compared progression-free survival (PFS) and overall survival (OS) using Kaplan–Meier and Cox regression analyses. Results: Among 426 glioma patients, 75 (17.6%) harbored a second non-brain tumor. Patients with multiple primaries showed significantly poorer OS (median 6 vs. 14 months, p = 0.002). No significant difference in PFS or OS was observed for patients in case the systemic tumor was in complete remission as compared to those with sole glioma. However, patients with progressive or stable systemic tumor had significantly worse outcomes regarding OS (p < 0.05). Conclusions: Our findings suggest that the presence of a second systemic malignancy is an independent prognostic factor for worse outcome. Further studies are mandated to elucidate genetic situations and refine therapeutic strategies for these patients. Full article

We report a unique pediatric acute myeloid leukemia (AML) case characterized by a CBFB::MYH11 fusion located on a supernumerary ring chromosome 16. Following diagnosis through comprehensive blood and bone marrow assays, the patient was enrolled in the Children’s Oncology Group (COG) study AAML1831 and randomized to the experimental treatment arm (Arm B). She received induction chemotherapy with CPX-351 (liposomal daunorubicin and cytarabine), gemtuzumab and ozogamicin (GO), and the cardioprotectant dexrazoxane and achieved complete remission (CR). The patient completed the treatment with sustained CR for 18 months. This case represents a rare cytogenetic phenomenon that is not well-documented in the current literature. Through a review of relevant publications, we contextualize this case within the spectrum of core binding factor AML (CBF-AML), highlighting diagnostic approaches, treatment strategies, and prognostic implications, particularly in cases involving atypical CBFB::MYH11 fusions. The durable remission observed in this patient, despite the unusual cytogenetic presentation, provides valuable insights into therapeutic management. This report underscores the cytogenetic and molecular heterogeneity of CBFB::MYH11 AML and emphasizes the importance of comprehensive genetic profiling using advanced techniques such as chromosomal microarray and next-generation sequencing. Full article

Objectives: Endometrial carcinoma is the most common gynaecological cancer in developed countries, with both incidence and mortality rates continuing to rise globally. For women of reproductive age diagnosed with early-stage disease or endometrial intraepithelial neoplasia, fertility-preserving treatment should be considered to maintain the possibility of future childbearing. Effective fertility-sparing management requires a multidisciplinary approach that includes patient education, reduction in risk factors, accurate molecular and histological classification to guide targeted therapies, assisted reproductive technologies to improve early conception rates, and attention to the psycho-sexual well-being of patients to support treatment adherence. Methods: This retrospective cohort study analysed the clinicopathological features and treatment outcomes of thirteen patients who received fertility-preserving therapy between 2018 and 2023. Results: The mean age of the patients (n = 13) was 34.4 years, with a range of 20 to 41 years. The overall treatment response rate was 76.9%, including 69.2% complete and 7.7% partial responses. Stable disease was observed in 15.4% of cases, while progression occurred in 7.7%. Among those who achieved complete remission, in vitro fertilisation (IVF) was initiated in four cases, with two ongoing as of the time of data analysis. In one of the cases, after two unsuccessful assisted reproductive attempts, spontaneous conception occurred, resulting in the birth of a child. Conclusions: Our findings support the feasibility and success of fertility-preserving treatment in carefully selected patients, allowing the preservation of reproductive potential alongside oncological care. Full article

Objectives: Endometrial cancer is the most common gynaecologic malignancy, and its mortality rate is rising. Advanced or recurrent disease remains challenging because historically there have been limited therapeutic options. We aim to describe a complete and durable response to the HER2-directed antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in a heavily pretreated patient with HER2-positive, mismatch-repair-deficient metastatic serous endometrial cancer. Methods: A 72-year-old woman underwent hysterectomy, bilateral salpingo-oophorectomy, and staging procedures for FIGO stage IIIA, high-grade serous papillary endometrial carcinoma. Tumour profiling revealed dMMR, a p53 abnormal pattern, and HER2 overexpression (IHC 3+). She received carboplatin/paclitaxel plus avelumab, followed by pegylated liposomal doxorubicin and weekly paclitaxel. After progression on paclitaxel, off-label T-DXd was initiated. Molecular data (FoundationOne CDx) were collected, along with and serial imaging and CA125 assessments. Results: The patient developed cough after two cycles of T-DXd; interstitial lung disease was excluded, and treatment resumed with steroid cover. By December 2024, PET/CT demonstrated complete metabolic response, with resolution of vaginal-vault and para-aortic lesions and normalisation of CA125. Real-world progression-free survival exceeded eight months, with ongoing symptom improvement. Treatment was generally well tolerated; the principal adverse event was grade 3 neutropenia requiring dose reduction. No cardiotoxicity or interstitial lung disease occurred. Conclusions: This case illustrates that T-DXd can induce deep and durable remission in HER2-positive, dMMR metastatic serous endometrial cancer after multiple lines of therapy. It adds real-world evidence supporting further investigation of HER2-directed antibody–drug conjugates in gynaecologic malignancies, and underscores the need for confirmatory trials and refined biomarker-driven patient selection. Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, typically presenting with systemic symptoms and mediastinal involvement. Leukemia cutis (LC) and renal infiltration are rare, especially at disease onset. A 27-year-old man presented with a solitary scalp lesion without systemic symptoms or hematologic abnormalities. Histopathology revealed a blastoid lymphoid infiltrate with a T-ALL immunophenotype. Two weeks later, laboratory tests showed leukocytosis, lymphocytosis, and renal dysfunction. Imaging revealed a large mediastinal mass, scalp soft tissue involvement, and bilateral renal infiltration. Bone marrow biopsy confirmed T-ALL with a mature phenotype. FISH identified TRAD:NKX2 rearrangement and CDKN2AB deletion. The patient received three cycles of pediatric-inspired chemotherapy, achieving complete molecular remission and resolution of extramedullary disease. He subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling. Post-transplant complications included febrile neutropenia and mucositis. On day +100, he remained in minimal residual disease (MRD)-negative remission. This case illustrates a rare presentation of T-ALL with isolated skin involvement and renal infiltration at diagnosis, highlighting the importance of early biopsy and immunophenotyping of atypical skin lesions. Intensive chemotherapy followed by HSCT represents a viable strategy for young adults with high-risk T-ALL and extramedullary disease. Full article

Background: Acute myeloid leukemia (AML) is an aggressive and biologically diverse hematologic cancer that disproportionately affects older individuals. Despite advances in molecular profiling and therapy, long-term outcomes remain unsatisfactory. This nationwide registry was established to provide real-world insights into clinical characteristics, treatment strategies, and survival among adult AML patients in Turkey. Methods: The Turkish AML Registry Project (ClinicalTrials.gov Identifier: NCT05979675) combines retrospective and prospective data from 23 tertiary hematology centers. Adult patients diagnosed between January 2008 and July 2023 were included. Baseline demographics, European LeukemiaNet (ELN) 2017 risk groups, Eastern Cooperative Oncology Group (ECOG) performance status, treatment intensity, and targeted therapy use were analyzed. Response and survival outcomes were assessed using Kaplan–Meier methods. Results: The interim dataset included 891 patients (median age 58 years, 45.5% ≥60). Intensive chemotherapy, most commonly 7 + 3, was applied in 74.1%, while 25.9% received lower-intensity regimens. Targeted agents, mainly venetoclax, were incorporated more frequently into low-intensity therapies (19.1% vs. 3.4%, p < 0.001). Complete remission occurred in 70.2% after intensive and 35.9% after low-intensity therapy, improving to 51.4% with targeted agents. Median overall survival (OS) was 27.2 months, with 1-year OS rates of 54.1%, 28.9%, and 17.6% for favorable, intermediate, and adverse ELN groups (p < 0.001). ECOG 0–1 predicted superior survival (1-year OS 70.3% vs. 47.0%). Conclusions: Nationwide real-world evidence underscores the prognostic relevance of ELN risk and functional status in AML. While intensive chemotherapy remains central, combining targeted agents with low-intensity regimens improves outcomes in less fit patients and supports personalized treatment approaches. Full article

Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset. Full article

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with cure rates exceeding 80% due to advancements in treatment protocols and supportive care. However, in children with Down syndrome (DS), ALL (DS-ALL) presents distinct genomic and clinical challenges. These include mutations in Janus kinase 2 (JAK2), neuroblastoma RAS viral oncogene homolog (NRAS), and E1A-binding protein p300 (EP300), as well as cytokine receptor-like factor 2 (CRLF2) rearrangements—such as P2RY8-CRLF2 fusion—and intrachromosomal amplification of chromosome 21 (iAMP21). These aberrations are associated with poor prognosis and increased risk of relapse. The objective of this study was to present a unique DS-ALL case with five concurrent high-risk genomic lesions and to contextualize its management in light of existing literature, emphasizing minimal residual disease (MRD)-guided therapy and supportive care. Case Report and Results: We present the case of a three-year-old boy with DS and B-cell ALL (B-ALL), in whom multiple high-risk genomic features co-occurred. Despite these adverse prognostic markers, the patient achieved complete remission following an intensive high-dose induction protocol. We also discuss therapeutic strategies that aim at balancing individualized treatment approaches with optimized supportive care to reduce toxicity and minimize relapse risk. Conclusions: This case underlines the importance of comprehensive molecular diagnostics, serial MRD monitoring, and personalized multidisciplinary care in DS-ALL. Full article

Background: Primary lymphoma of peripheral nerves (PLPN) is a rare extranodal non-Hodgkin lymphoma that mimics benign nerve conditions, leading to diagnostic delays. This systematic review evaluates the clinical, radiological, and pathological features of PLPN, alongside diagnostic and therapeutic strategies. Materials and Methods: A systematic search was conducted across PubMed, Scopus, and Web of Science, and identified 23 studies reporting 27 cases of PLPN. Data on demographics, clinical presentation, diagnostics, treatment, and outcomes were extracted and synthesized qualitatively due to study heterogeneity. Results: The sciatic nerve was most involved (48.15%), followed by the ulnar (18.5%) and radial nerves (18.5%). The median age at diagnosis was 58 years, with symptoms including motor deficits (88.9%), sensory disturbances (74.1%), and pain (70.4%). B-cell lymphomas accounted for 81.5% of cases, predominantly diffuse large B-cell lymphoma. MRI findings were non-specific; however, diffusion-weighted imaging (DWI) showed diagnostic potential. Treatments included combination therapies (51.9%), chemotherapy (25.9%), and surgery. Complete remission was achieved in 70.8%, with a 2-year survival rate of 83.3%. Conclusions: PLPN is rare but likely underdiagnosed. Early recognition requires multidisciplinary collaboration, advanced imaging, and standardized protocols. Future research should focus on molecular characterization, diagnostic criteria, and treatment optimization to improve outcomes for this challenging condition. Full article

The therapeutic landscape of adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is undergoing a paradigm shift, driven by the development of immunotherapy-based “chemo-free” and “chemo-light’ regimens. These strategies aim to achieve high efficacy with reduced toxicity, particularly in older adults who may not tolerate intensive chemotherapy. In Philadelphia chromosome-positive (Ph+) BCP-ALL, the incorporation of ABL tyrosine kinase inhibitors (TKIs) with blinatumomab (CD3/CD19 bispecific T-cell engager) has shown remarkable efficacy, with some studies reporting molecular response rates in the range of 90–100% and long-term survival exceeding 80% without the need for intensive chemotherapy or allogeneic hematopoietic cell transplantation (allo-HCT). In Philadelphia-negative (Ph−) BCP- ALL, an immunotherapy-based combination of blinatumomab and inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate) has demonstrated high rates of complete remission and measurable residual disease (MRD) negativity, with manageable toxicity. While chimeric antigen receptor (CAR) T-cell therapy remains a transformative option for relapsed/refractory B-ALL, its integration into frontline treatment is still under investigation. Ongoing trials are evaluating the optimal sequencing and combinations of these agents and their potential to obviate the need for chemotherapy and/or allo-HCT in selected patients. As evidence continues to accumulate, chemo-free and chemo-light regimens, incorporating minimal chemotherapy with targeted agents to balance efficacy and reduced toxicity, are poised to redefine the standard of care for adults BCP-ALL, offering the possibility of durable remissions with reduced treatment-related morbidity. Full article

Background and Clinical Significance: Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive hematologic malignancy. The presence of genetic abnormalities often increases the complexity of AMKL. Among these, patients with monosomy 7 constitute a high-risk group associated with a poorer prognosis and greater chemoresistance. We report the case of a 10-year-old boy who had AMKL along with monosomy 7 and familial GATA2 deficiency. The case highlights the diagnostic and therapeutic challenges faced, as well as the critical importance of early genetic screening and timely hematopoietic stem cell transplantation (HSCT). Case Presentation: A 10-year-old boy presented with easy bruising and pancytopenia. AMKL was diagnosed with the help of a bone marrow biopsy and immunophenotyping. Genetic testing showed a GATA2 mutation and monosomy 7. Two induction cycles with daunorubicin and cytarabine were administered but failed to eliminate residual disease. The patient also developed pneumonia of a fungal origin. HSCT was delayed due to liver toxicity and elevated minimal residual disease (MRD). Azacitidine and venetoclax stabilized the disease, thereby allowing for successful haploidentical HSCT. The patient achieved complete remission with full donor chimerism. Conclusions: This case emphasizes the importance of early molecular diagnostics in pediatric AMKL. Identifying GATA2 mutations and monosomy 7 early can help guide risk stratification and the timing of HSCT. Multimodal therapy, which includes the use of infection control and targeted agents, is important for improving the outcomes in high-risk patients. Full article

This paper reports the first case in which a hyperlipidemic retriever (due to hypothyroidism) with a nasal tumor was successfully treated—achieving partial remission—and managed using a metronomic combination of chlorambucil (3.74 mg/m², SID) and prednisolone (0.28 mg/kg, SID) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months with nosebleeds visited the Bundang New York Animal Hospital in July 2023 after being diagnosed with nasal carcinoma. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated in two cycles and continued metronomically for 9 months without pause after the two cycles. The nasal exudate was significantly reduced. The size of the nasal tumor was monitored using computed tomography (CT) imaging at a referral hospital. Since the first occurrence of epistaxis, 18 months have passed (as of January 2025) and the nasal exudate is barely visible, and the vital signs and weight of the dog remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy completion without moderate side effects, and all the blood work was normalized, including hypercholesteremia. This study demonstrates that, in hyperlipidemic cancer patients, a prednisolone/chlorambucil metronomic combination which is cost-effective can be an alternative to tyrosine kinase inhibitors such as sorafenib, even when excluding the price. Through a literature review, the author also investigates the effect of the hyperlipidemic state on cancer, focusing on carcinoma and vascular endothelial growth factor (VEGF), as well as the RAS-RAF-MEK pathway, which is a target for tyrosine kinase inhibitors, in order to reveal the molecular mechanism of chlorambucil metronomic chemotherapy. Also, the author investigates the molecular pathway of carcinoma development in human hyperlipidemia patients through single-cell RNA sequence analysis using open public data, and discusses the molecular action of chlorambucil. Full article