Hematology/oncology And Stem Cell Therapy[JOURNAL]
Sun
200 papers
Impact of mental health on outcomes of patients with relapsed and/or refractory diffuse large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy.
Kharfan-Dabaja MA, Tsalatsanis A, Uyanik MS … +5 more , Sher T, Qin H, Aljurf M, Chavez JC, Kumar A
Hematol Oncol Stem Cell Ther · 2026 Jan-Mar 01 · PMID 42333073 · Publisher ↗
BACKGROUND: A diagnosis of cancer creates a stressful situation owing to the uncertainties related to the thought of possible suffering from complications associated with treatment toxicities, the fear of not responding...
BACKGROUND: A diagnosis of cancer creates a stressful situation owing to the uncertainties related to the thought of possible suffering from complications associated with treatment toxicities, the fear of not responding to the prescribed treatment, or death. The prevalence of mental health disorders is relatively higher in cancer patients vis-à-vis the general population. METHODS: We performed a retrospective cohort study to evaluate the impact of mental health disorders on outcomes of relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR T-cell) therapy using data from the TriNetX research network. RESULTS: A total of 1587 patients met the inclusion criteria (858 with a mental health diagnosis and 729 without). After propensity score matching for age and gender, 1320 patients were included in the analysis (660 in each group). The 1-year OS was higher in patients without a mental health disorder (76.0% versus 69.4%, P = 0.004). Patients with mental health disorders had a higher incidence of cytokine release syndrome (all grades) compared with those without (35.5% versus 27.6%, P < 0.001) and immune effector cell-associated neurotoxicity syndrome (all grades) (16.8% versus 10.1%, P < 0.001). CONCLUSIONS: These findings emphasize the importance of thorough psychiatric evaluation and management in patients receiving CAR T-cell therapy. Patients with mental health disorders may need significant assistance with coordinating medical services to better adhere to required care management. Future studies are needed to help determine whether preventive and real-time mental health interventions can favorably impact outcomes of these patients.
Cancer epidemiology in the Kingdom of Saudi Arabia, 2024.
Aljurf M, Al-Azemi N, Al-Zahrani AS … +13 more , Altwaijri Y, Aleid M, Alrawaji A, Nasiri A, Alotiby M, Al-Nemari A, Al-Alyani S, Al-Zamzami A, Al-Juhani A, Mellgren A, Almashhadi S, Fakih RE, Al-Asiri MA
Hematol Oncol Stem Cell Ther · 2026 Jan-Mar 01 · PMID 42333072 · Publisher ↗
BACKGROUND: Cancer represents a significant and evolving public health challenge in the Kingdom of Saudi Arabia, a nation undergoing rapid socioeconomic and epidemiological transitions. This study provides a comprehensiv...
BACKGROUND: Cancer represents a significant and evolving public health challenge in the Kingdom of Saudi Arabia, a nation undergoing rapid socioeconomic and epidemiological transitions. This study provides a comprehensive analysis of cancer incidence for the year 2024 based on data from the national population-based Saudi Cancer Registry. METHODS: We conducted a descriptive epidemiological analysis of data from the 2024 Saudi Cancer Incidence Report. Data on all newly diagnosed cancer cases among Saudi nationals, including in situ tumors, were extracted and analyzed. Crude incidence rates (CIRs) and age-standardized incidence rates (ASRs) per 100,000 population were calculated using the direct method, with the World Standard Population as the reference. The distribution of cancer cases by age, sex, and major cancer sites was examined, with a detailed analysis of the most common solid and hematological malignancies, including histological subtypes and stage at diagnosis. RESULTS: In 2024, a total of 22,473 new cancer cases were diagnosed among Saudi nationals, with a higher incidence in females (13,206 cases, 58.8%) than in males (9267 cases, 41.2%). The overall ASR was 181.8 per 100,000 for females and 141.2 per 100,000 for males. The most common cancer was breast cancer (20.8%). The ASR for Saudi females was 63.3, the median age at diagnosis was 53 years, and 60.7% were diagnosed at localized or in situ stages. Colorectal cancer ranked second and accounted for 13.1% of all cancers, with an ASR of 26.4 for males and 19.1 for females, and a male-to-female ratio of approximately 123 to 100. The median age at diagnosis was 61 years for males and 58 years for females, and 52.9% were diagnosed at localized stages. Thyroid cancer was the third most common cancer in Saudi Arabia (9.1%) of all newly diagnosed cancers. Females accounted for 76.1% of cases, while males accounted for 23.9% of cases, resulting in a male-to-female ratio of approximately 31 to 100. The median age at diagnosis was 43 years for females and 45 years for males. Most cases were identified at the localized stage (74%), and the ASR was 18.3 for females and 6.2 for males. Hematological malignancies constituted 12.2% of cancer cases, with non-Hodgkin lymphoma (NHL) and leukemia ranking as the fourth and sixth most common cancers, respectively. NHL had an ASR of 8.9 in males and 6.7 in females, with diffuse large B-cell lymphoma as the predominant subtype (50%). Leukemia had an ASR of 6.7 in males and 5.1 in females, with a bimodal age distribution. Corpus uteri cancer accounted for 7.3% of all cancers diagnosed in Saudi Arabia (ASR; 15.5). The median age at diagnosis was 62 years, and the majority of cases (73.8%) were diagnosed at a localized stage. CONCLUSION: The cancer burden in Saudi Arabia is characterized by a high and rising incidence of lifestyle-associated solid tumors, alongside a significant burden of hematological malignancies with unique regional features. The observation of a low median age at diagnosis for key cancers warrants further investigation into age-specific incidence rates, which has potential implications for screening and clinical management. These findings underscore the urgent need for tailored prevention, early detection, and treatment strategies. Continued surveillance through the Saudi Cancer Registry is important for monitoring trends and guiding evidence-based public health policies.
Progressive transformation of germinal centers: Bridging clinical and pathological insights for diagnostic precision.
Ben Lamine C, Bakshi NA, Mohammed S … +2 more , Fakih RE, Aljurf M
Hematol Oncol Stem Cell Ther · 2026 Jan-Mar 01 · PMID 42283520 · Publisher ↗
Progressive Transformation of Germinal Centers (PTGC) is a rare, benign lymphoid condition that presents considerable diagnostic challenges due to its overlapping histological and immunophenotypic features with certain l...
Progressive Transformation of Germinal Centers (PTGC) is a rare, benign lymphoid condition that presents considerable diagnostic challenges due to its overlapping histological and immunophenotypic features with certain lymphomas, especially nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma. PTGC typically manifests as localized, nontender lymphadenopathy, and while the clinical course is usually indolent, a small subset of patients may experience progression to lymphoma. Given the potential for misclassification and overtreatment, there is a need for heightened diagnostic accuracy and clinical awareness. This review provides an updated, comprehensive synthesis of clinical features, histopathology, immunophenotyping, molecular diagnostics, and management strategies. Emphasis is placed on integrating multidisciplinary data to achieve diagnostic clarity, appropriately manage patient care, and monitor for rare cases of transformation. The review also includes recent literature on immunohistochemical and molecular patterns that improve the distinction between PTGC and malignant lymphoproliferative diseases.
The Two-Step Allogeneic Stem Cell Transplant Is Associated with Excellent Engraftment, Improved Survival and Low Nonrelapse Mortality in Patients with Myelofibrosis.
Bi X, Rashid S, Filicko-O'Hara J … +6 more , Van Galen J, O'Hara W, Wagner JL, Grosso D, Flomenberg N, Gergis U
Hematol Oncol Stem Cell Ther · 2026 Jan-Mar 01 · PMID 42170684 · Publisher ↗
Myelofibrosis is a chronic myeloproliferative disorder primarily affecting older adults, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. However, HSCT for myelofi...
Myelofibrosis is a chronic myeloproliferative disorder primarily affecting older adults, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. However, HSCT for myelofibrosis presents significant challenges, including high nonrelapse mortality (NRM) and an increased risk of graft failure. In this 20-year retrospective study, we evaluated outcomes for 32 myelofibrosis patients who underwent HSCT at our institution, with particular focus on a two-step transplant approach designed to optimize T-cell dosing by separating the lymphoid and myeloid graft components, with cyclophosphamide administered after the lymphoid infusion and before infusion of CD34-selected stem cells. Eighteen patients underwent transplantation using the two-step approach and demonstrated favorable outcomes, with 1-year and 5-year overall survival (OS) rates of 83% and 68%, respectively. NRM was reduced, with rates of 17% at 1 year and 23% at 5 years. Engraftment was robust, with median neutrophil and platelet recovery at 12 and 19 days, respectively, and a low graft failure rate of 5.9% despite the predominant use of reduced-intensity conditioning and haploidentical donors, compared with 17.5% graft failure among patients receiving a traditional one-step transplant. Across the entire cohort, OS was 66% at 1 year and 54% at 5 years, respectively, with NRM rates of 34% and 42% at 5 years, respectively. The cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was 17% each. These findings suggest that the two-step transplant platform is a viable and effective strategy for improving HSCT outcomes in myelofibrosis, providing lower NRM and favorable engraftment profiles. Further studies are warranted to validate these results and refine HSCT protocols to reduce transplant-related mortality and improve long-term survival in patients with myelofibrosis.
Hypophosphatemia as a Marker for Immune Effector Cell-Associated Neurotoxicity Syndrome in Chimeric Antigen Receptor T Cell Recipients.
Almashayekh A, Sulaiman S, Alaarag A … +14 more , Omaish R, Mekuria Z, Balts N, Henson JC, Vellanki S, Trikannad A, Spears G, Mohan-Lal B, Pandey T, Odueke A, Schinke C, Gentille-Sanchez C, Jain N, Alshawayat A
Hematol Oncol Stem Cell Ther · 2026 Jan-Mar 01 · PMID 42169662 · Publisher ↗
BACKGROUND: Hypophosphatemia is a common electrolyte abnormality in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Its relationship with immune effector cell-associated neurotoxicity syndrome (ICANS...
BACKGROUND: Hypophosphatemia is a common electrolyte abnormality in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Its relationship with immune effector cell-associated neurotoxicity syndrome (ICANS) remains incompletely understood. This study investigates the incidence, timing, and clinical correlations of hypophosphatemia and its relationship with ICANS. METHODS: We conducted a retrospective chart review of patients who received CAR-T therapy at an academic center. Hypophosphatemia was defined as <2.5 mg/dL post-CAR-T infusion. The timing of ICANS onset and phosphorus (Pi) nadir were collected. Associations were assessed using chi-square or Fisher's exact tests. Ordinal logistic regression, linear regression, Cox regression and time-dependent Cox model evaluated the relationship between ICANS and Pi trends. RESULTS: Of 186 CAR-T recipients, 75 had non-Hodgkin's lymphoma (NHL), 103 had multiple myeloma (MM), and 8 had acute lymphoblastic leukemia. Hypophosphatemia occurred in 71.5% (95% CI: 64.4%-77.8%), with an incidence of 82.6% in patients receiving idecabtagene-vicleucel (Abecma) and 75.4% in patients receiving axicabtagene-ciloleucel (Yescarta) ( P = 0.002). Among those with hypophosphatemia, mean nadir phosphate was 1.78 mg/dL (95% CI: 1.7-1.84), occurring at a median of 5.94 days post-infusion (95% CI: 5.12-6.7; SD 4.78). Hypophosphatemia was associated with increased ICANS risk (hazard ratio 2.87, 95% CI 1.63-5.1, P = 0.001) and typically preceded ICANS by a median of 2 days (95% CI: 0.83-3.2, P < 0.001 Wilcoxon). In NHL patients, lower nadir phosphate predicted higher ICANS grade ( β = -1.76, P < 0.001). We concluded that Hypophosphatemia is common post-CAR-T and typically occurs within the first week. Its temporal association with ICANS suggests a potential biological link. Hypophosphatemia may serve as an early predictor of ICANS, warranting further study of phosphate correction as a preventive strategy and potentially a predictor marker.
Effect of Somatic Variants Post Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Iqbal M, Mahadevia H, Li Z … +9 more , Blumenfeld S, Murthy H, Foran J, Roy V, Badar T, Ayala E, Kharfan-Dabaja MA, Fan YS, Jiang L
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41846455 · Publisher ↗
Measurable residual disease (MRD) has established prognostic significance in patients with myeloid disorders; however, there is limited data regarding its prognostic and predictive value and the optimal technique for mea...
Measurable residual disease (MRD) has established prognostic significance in patients with myeloid disorders; however, there is limited data regarding its prognostic and predictive value and the optimal technique for measurement in the setting of post allogeneic hematopoietic cell transplantation (allo-HCT). A multi-gene next generation sequencing (NGS) panel can overcome the limitations of conventional techniques for measurement of MRD and can shed light onto the longitudinal evolution and genomic complexity of patients undergoing allo-HCT for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, patients with AML or MDS who underwent their first allo-HCT and completed NGS testing at day +100 and were in a state of morphological remission were identified from the transplant registry of Mayo Clinic in Florida. The primary aim was to evaluate the prognostic impact of somatic variants detected via NGS at day +100 post allo-HCT on long-term outcomes. In total, 105 patients who underwent allo-HCT for AML and MDS and completed NGS testing on day +100 were included in the study population. Seventeen patients were found to have detectable variants, and 88 patients were without a detectable variant. At a median follow up of 1.4 years (0.1-5.5), presence of any variant at day +100 was associated with inferior 4-year overall survival (OS) (32% vs. 69%, P < 0.001), decreased progression free survival (PFS) (34% vs. 61%, P < 0.001), and a higher incidence of relapse (64% vs. 23%, P < 0.001). In univariate models, a lower Karnofsky performance score and presence of variants post allo-HCT remained significantly associated with inferior OS, higher relapse incidence, and a decreased PFS. The presence of variants at day +100 post allo-HCT remained significant in multivariate models for relapse ( P = 0.002) but not for OS ( P = 0.06) and PFS ( P = 0.08). These results indicate that the presence of detectable somatic variants at day +100 is associated with poor long-term outcomes and are predictive of a higher incidence of relapse.
Characteristic and Clinical Outcomes of Localized Gastric Cancer: A Real-World Experience.
Aljuhani A, Aseafan M, Sheikh A … +4 more , Alhanash A, Alshamsan B, Elhassan T, Bazarbashi S
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41846430 · Publisher ↗
BACKGROUND AND OBJECTIVE: Gastric and gastroesophageal junction (G/GEJ) cancers, with their poor prognosis, pose management challenges. Treatments like perioperative chemotherapy, neoadjuvant chemoradiotherapy, and adjuv...
BACKGROUND AND OBJECTIVE: Gastric and gastroesophageal junction (G/GEJ) cancers, with their poor prognosis, pose management challenges. Treatments like perioperative chemotherapy, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy aim to improve outcomes. The 5-fluorouracil, leucovorin, oxaliplatin, docetaxel (FLOT) regimen has shown promise in enhancing survival. The effectiveness of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) and intra-operative radiotherapy (IORT) is still being studied. We investigated the roles of different prognostic factors and therapeutic interventions in patients with localized G/GEJ. METHODS: A retrospective study of 65 patients diagnosed with localized G/GEJ cancer and treated at a tertiary cancer center from January 2018 to December 2022. RESULTS: Over a median follow-up of 23 months (range: 15.2-37.0 months), we observed a median progression-free survival (PFS) of 20 months (95% confidence interval [CI]: 8.5-31.5) and a median overall survival (OS) of 35.0 months (95% CI: 19.5-50.5). Univariate analysis revealed no statistically significant differences in OS across treatment subgroups. Notably, patients without prophylactic HIPEC/IORT and those treated with perioperative 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) showed numerically longer PFS and OS than their counterparts. CONCLUSION: Our study supports the effectiveness of perioperative chemotherapy in localized gastric cancer, aligning with international data. However, it does not confirm FLOT's superiority over FOLFOX or the benefit of adjuvant HIPEC/IORT in these patients.
Epidemiology and Outcomes of Hospitalized Patients with Hematological Malignancy and Acute Respiratory Failure.
Ponnapalli A, Sharma A, Fatima M … +2 more , Arora AK, Soubani AO
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41788040 · Publisher ↗
INTRODUCTION: Patients with hematologic malignancies are at increased risk for acute respiratory failure (ARF), which is a leading cause of intensive care units admission and mortality in this population. This study aime...
INTRODUCTION: Patients with hematologic malignancies are at increased risk for acute respiratory failure (ARF), which is a leading cause of intensive care units admission and mortality in this population. This study aimed to characterize the epidemiology, clinical outcomes, and healthcare utilization associated with ARF in hospitalized patients with hematologic malignancies, using a nationally representative dataset. METHODS: We conducted a retrospective cohort study using the 2016-2019 National Inpatient Sample. Adult hospitalizations with hematologic malignancies were identified using International Classification of Disease, Tenth Revision, Clinical Modification codes and stratified by presence of ARF and by use of invasive mechanical ventilation (IMV). RESULTS: Among 2,427,924 hospitalizations for hematologic malignancies, 304,515 (12.5%) had ARF. Compared to non-ARF admissions, admissions with ARF were older, with a mean age of 70.1 versus 65.9 years, had more comorbidities, with 61.1% having a Charlson comorbidity index greater than 3 compared to 40.9%, and experienced higher rates of sepsis (71.6% vs. 38.3%) and acute kidney injury (AKI) (43.5% vs. 20.1%). In-hospital mortality among admissions with ARF was 22.7% compared to 2.2% in those without ARF. These admissions also had longer hospital stays (10.95 days vs. 6.58 days) and incurred higher hospital costs ($37,645 vs. $19,505). Among admissions with ARF, 84,260 (27.7%) required IMV. This subgroup had the highest mortality at 49.7%, a mean length of stay of 16.3 days, and incurred the highest hospital costs at $69,923. IMV use was also associated with higher complication rates, including sepsis (80.4%) and AKI (62.4%). Increased age, AKI, and neutropenia were independent predictors of in-hospital mortality among admission with hematological malignancies who required invasive mechanical ventilation. CONCLUSION: ARF affects more than one in 10 hospitalized patients with hematologic malignancies. Although improved compared to historical data, it remains linked to increased mortality and healthcare utilization, particularly among those requiring IMV. These findings highlight the need for early risk stratification and targeted interventions to improve outcomes in this high-risk population.
Patients with Fanconi Anemia Have an Increased Incidence of Diabetes Mellitus After Allogeneic Stem Cell Transplantation.
Ayas M, Siddiqui K, Al-Jefri A … +6 more , Ghemlas I, Al-Saedi H, Al-Enazi A, Khan S, Al-Seraihi A, Al-Ahmari A
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41630169 · Publisher ↗
Abstract loading — click title to view on PubMed.
Epidemiology and Outcomes of Hepatic Veno-Occlusive Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Descriptive Analysis of the U.S. National Inpatient Sample.
Sharma A, Surapaneni S, Sharma A … +2 more , Maheshwari R, Soubani AO
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41630155 · Publisher ↗
INTRODUCTION: Hepatic veno-occlusive disease (HVOD), or sinusoidal obstruction syndrome (SOS), is a potentially liefe-threatening complication following allogeneic stem cell transplantation (allo-SCT). Historically, HVOD...
INTRODUCTION: Hepatic veno-occlusive disease (HVOD), or sinusoidal obstruction syndrome (SOS), is a potentially liefe-threatening complication following allogeneic stem cell transplantation (allo-SCT). Historically, HVOD has affected up to 60% of allo-SCT recipients, with reported mortality rates exceeding 75% in severe cases. The approval of defibrotide in 2016 represented a major therapeutic milestone, significantly improving outcomes in high-risk patients. Despite this advancement, large-scale data on HVOD epidemiology & outcomes in allo-SCT recipients remain limited. This study aims to address these gaps & offer updated insights into its clinical impact. METHODS: We utilized National Inpatient Sample (2016-2020) to examine factors associated with HVOD in allo-SCT recipients. Admissions for allo-SCT & HVOD were identified using International Classification of Diseases, Tenth Revision. Baseline characteristics, including patient demographics, hospital characteristics, comorbidities, complications & outcomes were compared between allo-SCT admissions with & without HVOD. Categorical variables were analyzed by χ ² test (%), & continuous variables by adjusted Wald's test (mean±SD). RESULTS: During the study period, 200 allo-SCT admissions with HVOD were identified. HVOD admissions were younger (45.05 vs. 52.42 years; P =0.0045) & were more likely to be female (43.72% vs. 25%; P =0.0191). They had higher rates of acute graft-versus-host disease (GVHD) (17.5% vs. 6.47%; P =0.0043), acute respiratory failure (32.5% vs. 8.37%; P< 0.001), & acute kidney injury (50% vs. 20.66%; P< 0.001). Hepatic complications, including portal hypertension (7.5% vs. 0.52%; P< 0.001), hepatic encephalopathy (12.5% vs. 0.28%; P <0.001), cirrhosis (7.5% vs. 0.07%; P< 0.001), ascites (37.5% vs. 1.97%; P< 0.001) & spontaneous bacterial peritonitis (2.5% vs. 0.06%; P< 0.001) were also more common in this cohort. HVOD was associated with worse outcomes, including longer hospital stays (45.5 vs. 29.51 days; P <0.001) & over 6 times higher in-hospital mortality (30% vs. 4.72%; P <0.001). HVOD also imposed a greater economic burden, with more than double mean total hospitalization charges ($1,321,650 vs. $541,391.1; P <0.001) & nearly triple hospitalization costs ($358,463.2 vs. $141,464.1; P <0.001). CONCLUSION: This study describes HVOD-specific characteristics in allo-SCT admissions. Patients with HVOD were younger, had higher comorbidity burden, & showed increased rates of acute GVHD, multiorgan dysfunction, & hepatic complications. They also faced high in-hospital mortality, longer hospital stays, & greater healthcare costs.
Antibody-Drug Conjugates (ADCs) for Breast Cancer Therapeutic Landscape: Concept and Mechanisms of Action.
Paz-Manrique R, Pinto JA, Gomez Moreno HL
Hematol Oncol Stem Cell Ther · 2025 Oct-Dec 01 · PMID 41630133 · Publisher ↗
The concept of a "magic bullet" in oncology-first envisioned by Paul Ehrlich-has evolved into one of the most dynamic areas in precision cancer therapeutics: antibody-drug conjugates (ADCs). These biopharmaceuticals comb...
The concept of a "magic bullet" in oncology-first envisioned by Paul Ehrlich-has evolved into one of the most dynamic areas in precision cancer therapeutics: antibody-drug conjugates (ADCs). These biopharmaceuticals combine the selectivity of monoclonal antibodies with the potency of cytotoxic agents through specialized linkers, achieving targeted delivery of chemotherapeutic compounds to malignant cells while minimizing systemic toxicity. This narrative review explores the molecular foundations, pharmacologic mechanisms, and clinical evolution of ADCs, emphasizing their transformative impact on breast cancer management. ADCs are structured around three essential components: an antibody that binds a tumor-specific antigen, a linker that ensures controlled payload release, and a cytotoxic drug that induces apoptosis once internalized. The interaction of the ADC-antigen complex leads to endocytosis, lysosomal degradation, and payload liberation. Depending on the properties of the linker and the permeability of the cytotoxic payload, the cytotoxic effect can extend to neighboring cells-a phenomenon termed the bystander effect. Advances in linker chemistry, such as the use of acid-labile, enzyme-labile, or disulfide-cleavable bonds, together with the humanization of antibody backbones, have significantly improved pharmacokinetics, stability, and safety. The evolution of ADC generations illustrates progressive refinements in bioengineering and therapeutic efficacy. First-generation ADCs, such as Gemtuzumab ozogamicin, demonstrated the proof of concept but suffered from high immunogenicity, poor selectivity, and heterogeneous drug-antibody ratios. Second-generation ADCs introduced stable linkers and humanized antibodies, exemplified by Ado-trastuzumab emtansine (T-DM1), which targets the HER2 receptor in breast cancer. Clinical trials such as EMILIA and HER2CLIMB-02 confirmed improved survival outcomes and reduced toxicity compared with conventional chemotherapy. Third-generation ADCs, including Trastuzumab deruxtecan and Sacituzumab govitecan, incorporate site-specific conjugation, higher drug-to-antibody ratios, and potent payloads capable of inducing bystander killing even in tumors with low antigen expression. Landmark studies such as DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, ASCENT, and TROPiCS-02 have positioned these agents as pivotal therapies across HER2-positive, HER2-low, and triple-negative breast cancer subtypes. Despite these advances, resistance mechanisms remain a significant challenge. These include antigen downregulation, overexpression of efflux pumps, impaired intracellular trafficking, and reduced payload activation. Nevertheless, the modular architecture of ADCs allows iterative optimization of their antibody, linker, and payload components to overcome these barriers. Future developments are exploring bispecific ADCs that target multiple antigens, radiolabeled or immune-activating conjugates, and masked ADCs engineered for selective activation within tumor microenvironments, all of which aim to further refine selectivity, potency, and therapeutic benefit. In conclusion, ADCs exemplify the convergence of molecular biology, immunology, and medicinal chemistry in the pursuit of precision oncology. Their progressive evolution from concept to clinic not only validates Ehrlich's century-old vision but also heralds a new therapeutic era in which cancer treatment achieves unprecedented specificity, efficacy, and improvement in patient outcomes.
Myeloablative and Reduced Intensity Allogeneic Transplant in Patients with Myeloproliferative Neoplasms.
Trunk AD, Chen Y, Gerds AT … +9 more , Jain A, Mukherjee S, Balderman S, Carraway H, Hamilton BK, Sobecks R, Kalaycio M, Sauter C, Brunstein C
Hematol Oncol Stem Cell Ther · 2025 Sep · PMID 40937524 · Publisher ↗
BACKGROUND: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potentially curative treatment for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). Older age, comorbidities, and often advanced d...
BACKGROUND: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potentially curative treatment for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). Older age, comorbidities, and often advanced disease make patient selection and optimal transplant timing challenging. This study sought to understand allo-HCT outcomes for these myeloproliferative neoplasms in a contemporary era, including molecular data, to define a uniform transplant approach. METHODS: Retrospective analysis was performed on patients with MF or CMML who received allo-HCT at the Cleveland Clinic between January 1, 2010 and April 1, 2023. All donor types and graft sources were included. MF and CMML outcomes were analyzed separately. RESULTS: Fifty-nine MF and 33 CMML patients were included. JAK2 V617F was detected in 57.6% of MF patients; only 34 (57.6%) had next-generation sequencing (NGS) performed. Most MF transplants were reduced intensity (RIC; 69.5%) and peripheral blood stem cell (PBSC; 91%). At median follow-up of 41 months, 28/59 (47.5%) MF patients were alive. MF patients who were JAK2+ with additional cytogenetic changes or concurrent mutations had better overall survival. In CMML, 69.7% had myeloid NGS, with ASXL1 identified in 51.9% of cases. Most transplants were RIC (66.7%) and PBSC (72.7%). At median follow-up of 46.8 mos, 13/33 (39.4%) patients were alive. Relapse accounted for 9/20 CMML deaths; 8 of these received RIC. Mutational signature did not significantly impact survival, though the presence of any cytogenetic aberrancy was associated with worse OS (12 mos, 95% CI, 7.13-NA vs. 24.2 mos, 9.6-NA; P = 0.19). CONCLUSION: For MF and CMML, older patients (≥65) and RIC transplants trended toward worse survival. Strategies to reduce relapse and optimize patient selection utilizing molecular and cytogenetic data should be considered.
Patterns of Graft-Versus-Host Disease (GvHD) Prevention Practices in the Eastern Mediterranean (EM) Region: A Worldwide Network for Blood & Marrow Transplantation (WBMT) Global Study.
Muhsen IN, Niederwieser D, Garderet L … +40 more , Penack O, Greinix HT, El Fakih R, Abdeljelil NB, Abosoudah I, Alamoudi S, Albeihany A, Al Daama SA, Alshahrani MH, Alshemmari S, Al-Khabori M, Almasari A, Al Rawas A, Askar M, El-Cheikh J, Bekadja MA, Benakli M, Borhany M, El Kababri M, Halahleh K, Hamidieh AA, Hammad M, Ibrahim A, Kanfar S, Khalaf MH, Marei M, Mir MA, Monagel D, Quessar A, Rihani R, Shabbir-Moosajee M, Shaheen M, Sultan AM, Vaezi M, Rondelli D, Koh MBC, Peric Z, Atsuta Y, Chaudhri N, Aljurf M
Hematol Oncol Stem Cell Ther · 2025 Sep · PMID 40937504 · Publisher ↗
BACKGROUND: Preventing graft vs. host disease (GvHD) after allogeneic hematopoietic stem cell transplant (allo-HSCT) is essential to improving the outcomes and quality of life of allo-HSCT recipients. Little is known abo...
BACKGROUND: Preventing graft vs. host disease (GvHD) after allogeneic hematopoietic stem cell transplant (allo-HSCT) is essential to improving the outcomes and quality of life of allo-HSCT recipients. Little is known about the trends and patterns of global GvHD prevention practices. Thus, the Worldwide Network for Blood & Marrow Transplantation global GvHD project aims to understand and describe the patterns of GvHD prevention and management worldwide. This article discusses GvHD prevention practices in the East Mediterranean (EM) region. MATERIALS AND METHODS: A questionnaire was distributed electronically to the EM region transplant centers and filled out by program directors or designees. Responses were received between December 2022 and June 2023. The questionnaire had 33 items, with 7 sections focusing on the different commonly used agents in GvHD practices (including calcineurin inhibitors, in vivo T-cell depletion, and methotrexate [MTX]). RESULTS: Thirty responses from 26 institutions were received from 11 countries in the EM region. All programs perform matched-related donor (MRD) transplants, 29 perform haploidentical transplants, and 19 perform matched unrelated donor (MUD) transplants. Cyclosporine (CsA) with MTX was the preferred regimen in both myeloablative (79%) and reduced intensity conditioning (50%). CsA was more widely used compared to tacrolimus (Tac) (93% vs. 57%). The duration of calcineurin inhibitor use before initiating taper in recipients with malignant and non-malignant disorders was similar between CsA and Tac. All programs reported routine monitoring of calcineurin inhibitor levels. Twenty-nine programs reported using MTX, administering it over 3-4 days post-HSCT. The use of different in vivo T-cell depletion therapies was commonly reported, particularly anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). ATG use was reported by 77% and 79% of programs for MRD and MUD HCT, respectively. Additionally, most programs (97%) reported using PTCy mainly for haploidentical transplants. Among centers using PTCy, most programs reported using a dose of 50 mg/kg, and the most common schedule was Days +3 and +4. However, 12 programs reported using lower doses of 25-40 mg/kg or spaced-out schedules (Days +3 and +5). CONCLUSION: This study describes the different practices of GvHD prophylaxis in the EM region. Our results show that allo-HSCT centers in the EM regions utilize most standard-of-care agents, and most practices are in alignment with evidence-based guidelines.
Allogeneic hematopoietic cell transplantation as the standard of care for blastic plasmacytoid dendritic cell neoplasm in first complete remission.
Kharfan-Dabaja MA
Hematol Oncol Stem Cell Ther · 2025 Sep · PMID 40937492 · Publisher ↗
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic disorder derived from precursors of plasmacytoid dendritic cells, with a generally aggressive clinical course. Tagraxofusp, a first-in-class CD12...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic disorder derived from precursors of plasmacytoid dendritic cells, with a generally aggressive clinical course. Tagraxofusp, a first-in-class CD123-directed antibody conjugate comprising human interleukin-3 and truncated diphtheria toxin, represents a welcome addition to the treatment armamentarium for BPDCN. Allogeneic hematopoietic cell transplantation (allo-HCT) is a treatment modality with curative potential in patients with BPDCN, based on data derived from registry studies, as well as multicenter and single-center retrospective studies. Several studies and a systematic review/meta-analysis have shown superior survival when patients undergo allo-HCT in first complete remission (CR1). In younger or fit patients, a myeloablative conditioning (MAC) allo-HCT regimen is the preferred approach whenever an allograft is indicated. Incorporating total body irradiation within the MAC regimen has been shown to improve progression-free survival, disease-free survival, and overall survival. However, MAC regimens have limited applicability in older, frail, or less fit patients, for whom reduced-intensity conditioning is the most appropriate approach. Several questions remain unanswered-namely, the potential benefit of post-transplant consolidation or maintenance strategies to mitigate the risk of relapse or progression, and the role of next-generation sequencing as a prognostic tool and for better defining depth of remission and measurable residual disease, among others. We believe that further improvement in the prognosis of BPDCN will require large collaborative efforts, considering the rarity of this disease.
Impact of TMPRSS6 gene polymorphism on iron overload among children with sickle cell disease.
El-Bostany EA, Elghoroury EA, Thabet EH … +8 more , Abdelhamid N, Hamed HM, Salama N, Rashad AA, Abd El Aziz SH, Kamel S, Awadallah E, Salama II
Hematol Oncol Stem Cell Ther · 2025 Sep · PMID 40936486 · Publisher ↗
OBJECTIVE/BACKGROUND: Iron overload is a significant problem in transfusion-dependent children with sickle cell disease (SCD). The molecular mechanisms underlying the progression to iron overload in SCD are poorly unders...
OBJECTIVE/BACKGROUND: Iron overload is a significant problem in transfusion-dependent children with sickle cell disease (SCD). The molecular mechanisms underlying the progression to iron overload in SCD are poorly understood. Our aim is to investigate how TMPRSS6 single nucleotide polymorphisms (SNPs) affect iron status in children with SCD. METHODS: A case-control study was conducted for 61 SCD children, aged 6-18 years, and a control group of 42 age-sex matched healthy children. Real time polymerase chain reaction (PCR) was performed to determine the SNPs of rs11704654 C/T, rs4820268 A/G and rs855791 A/G of TMPRSS6 gene and iron overload parameters were measured. RESULTS: There was a significant protective association between SCD and the rs11704654 polymorphism (OR [95% CI)] = 0.36(0.15-0.86), P < 0.05. In contrast, a significant association between rs4820268, rs855791 polymorphisms and SCD risk was found, using the dominant genetic model (P < 0.05). The hepcidin gene expression and hepcidin/iron ratio were significantly higher in rs4820268 AG genotype compared to the minor homozygote GG genotype. Meanwhile, there was no significant difference between rs11704654, rs855791 genotypes and iron status parameters. CONCLUSION: TMPRSS6 gene polymorphism influences susceptibility to SCD and contributes to the regulation of iron status. The rs4820268 AG genotype provides protection against iron overload. Modulation of iron status by TMPRSS6 SNPs represents a promising target for future therapy.
Epidemiology and outcomes of hospitalized patients with lung cancer and acute respiratory failure: National inpatient database analysis.
Tripcovici M, Sharma A, Clopton BJ … +2 more , Kurtz D, Soubani AO
Hematol Oncol Stem Cell Ther · 2025 Sep · PMID 40936468 · Publisher ↗
BACKGROUND: Acute respiratory failure (ARF) is common in lung cancer patients and could be related to tumor progression, effects of treatment, or comorbid illnesses. Data on the short-term outcomes of these patients, esp...
BACKGROUND: Acute respiratory failure (ARF) is common in lung cancer patients and could be related to tumor progression, effects of treatment, or comorbid illnesses. Data on the short-term outcomes of these patients, especially those requiring invasive mechanical ventilation (IMV), remain scarce. METHODS: The National Inpatient Sample database (2016-2019) was used to identify lung cancer admissions using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. ARF and IMV subgroups within lung cancer hospitalizations were identified using ICD-10-CM codes. Baseline variables were analyzed using χ2 test for categorical data and adjusted Wald tests for continuous data. Results were reported as percentages and mean ± standard deviation. RESULTS: We identified 581,805 (24.7%) admissions for lung cancer with ARF during the study period. All-cause inpatient mortality was six times higher in lung cancer admissions with ARF compared to the non-ARF cohort (18.50% vs. 3.19%; P < 0.001). Similarly, lung cancer admissions with ARF that required IMV had significantly higher mortality compared to the cohort that did not require IMV (44.86% vs. 12.59%; P < 0.001). Lung cancer admissions with ARF requiring IMV had longer stay in the hospital (11.19 vs. 6.69 days; P < 0.001). The total hospitalization cost was more than two times higher for lung cancer admissions with ARF requiring IMV ($40,024.2 vs. $16,260.5; P < 0.001). CONCLUSIONS: In this largest study to date, we provide insight into the incidence and outcomes of lung cancer admissions with ARF. Lung cancer admissions with ARF, especially those requiring IMV, were associated with worse outcomes, longer hospital stays, and significantly higher healthcare costs. Compared to historical data, the outcomes in this large database have improved.
Cytomegalovirus infection in pediatric haploidentical stem cell transplantation.
AlSweed A, Aljumaah S, AlSaedi H … +3 more , Alruwaisan H, Alhuthil R, Al-Hajjar S
Hematol Oncol Stem Cell Ther · 2025 Apr-Jun 01 · PMID 40718982 · Publisher ↗
BACKGROUND: Human cytomegalovirus (CMV) is a major source of morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT). CMV replication is mainly controlled by T-cell-mediated immunity. Despite...
BACKGROUND: Human cytomegalovirus (CMV) is a major source of morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT). CMV replication is mainly controlled by T-cell-mediated immunity. Despite treatment, CMV reactivation continues to have a significant adverse impact on post-transplant outcomes. In this study, we examine the clinical aspects and risk factors for CMV reactivation and disease, and the effect of therapeutic interventions in pediatric patients who underwent HSCT. METHODS: This retrospective, single-center study included pediatric patients who underwent haploidentical HSCT at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, from 2013 to 2018. RESULTS: A total of 94 HSCT recipients were included: 46 (48.94%) females and 48 (51.06%) males, with a median age of 5 years [interquartile range (IQR): 1.2-8.7]. As for donors, 57 (60.64%) were males and 37 (39.36%) were females, with a median age of 30.7 years (IQR: 23.0-35.3). CMV reactivation occurred in 52 (55.32%) of the HSCT patients. The overall mortality rate was 12.77% (12/94), and of those, 83.33% (10/12) were CMV positive. However, no patient developed CMV pneumonitis, gastritis, or colitis, and CMV was not identified as the direct cause of death. Regarding CMV risk factors, higher recipient age and the presence of acute graft-versus-host disease were significantly associated with CMV reactivation (P < 0.05). CONCLUSION: Preventing CMV infection significantly impacts the post-transplant course, especially in the setting of mismatched donors. This study showed that preventing CMV by preemptive therapy revealed an undetectable rate of 78.85%. Current polymerase chain reaction (PCR)-directed surveillance and prophylaxis have lowered the incidence of CMV disease and persistent DNAemia.
Relevant biomarkers in acute graft-versus-host disease secondary to transplantation of hematopoietic stem cells.
Manosalva JP, Quimbaya P, Bustos RH … +3 more , Perdomo-Arciniegas AM, Bonilla X, Oliveros H
Hematol Oncol Stem Cell Ther · 2025 Apr-Jun 01 · PMID 40718981 · Publisher ↗
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Specific biomolecules identified in samples from patients with aGVHD have been correlated with the...
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Specific biomolecules identified in samples from patients with aGVHD have been correlated with the diagnosis, prognosis, prediction, and treatment response of aGVHD. In this review, we summarize the most promising biomarkers with clinical relevance for aGVHD. Articles were identified through a literature search in PubMed, EMBASE, and Cochrane databases up to November 1, 2022. All identified papers were manually reviewed. We included studies written in English or other languages that investigated biomarkers in GVHD. A total of 3733 studies were identified, of which 32 met the inclusion criteria and were included in this scoping review. Twenty-one different biomarkers were reviewed, including 11 plasma biomarkers and 9 organ-specific biomarkers. Nearly all biomarkers had distinct roles in aGVHD pathophysiology, while some were combined into biomarker panels along with clinical responses. The study of biomarkers in aGVHD has significantly expanded in recent years, encompassing various aspects of the disease. Currently, biomarker panels have shown the most promising results in terms of sensitivity and specificity for diagnosis and prognosis. Biomarkers hold great potential as tools for the reproducible prediction of aGVHD onset, severity, and treatment outcomes, although they remain unproven in routine clinical practice.
A Critical Review of CAR-T Therapies for Glioblastoma: What's Wrong with the Current Attempts?
Belokon SV, Kukarskaya VA, Klabukov ID … +5 more , Shestakova VA, Ivanov SA, Shegay PV, Kaprin AD, Baranovskii DS
Hematol Oncol Stem Cell Ther · 2025 Apr-Jun 01 · PMID 40539476 · Publisher ↗
Today, CAR-T therapy has been widely acknowledged as a "gold standard" treatment for certain hematologic diseases. There is a relatively small but enhancing body of clinical trials studying the effectiveness of CAR-T in...
Today, CAR-T therapy has been widely acknowledged as a "gold standard" treatment for certain hematologic diseases. There is a relatively small but enhancing body of clinical trials studying the effectiveness of CAR-T in treating glioblastoma, known as the most common and aggressive brain tumor in adults. Despite the promising findings, currently available data is still erratic. We aimed to overview the recent clinical attempts to apply CAR-T therapy as the treatment strategy for glioblastoma and highlight non-obvious problems occurring: flaws in the study design with suspicious inclusion criteria, absence of narrow nosologic focus, poor validation or even nonvalid imaging technologies and inconveniencing efficacy evaluation. We also discussed further upcoming advanced approaches for CAR-T cell manufacturing. We are convinced that our review could help to define the right place for CAR-T therapy in glioblastoma treatment strategy and would pave the way for future successful clinical trials.
Acute and chronic graft-versus-host disease treatment and management in the Eastern Mediterranean region: A Worldwide Network for Blood and Marrow Transplantation survey.
Muhsen IN, Niederwieser D, Garderet L … +40 more , Penack O, Greinix HT, El Fakih R, Abdeljelil NB, Abosoudah I, Alamoudi S, Albeihany A, Al Daama SA, Alshahrani MH, Alshemmari S, Al-Khabori M, Almasari A, Al Rawas A, Askar M, Bazarbachi A, Bekadja MA, Benakli M, Borhany M, Kababri ME, Halahleh K, Hamidieh AA, Hammad M, Ibrahim A, Kanfar S, Khalaf MH, Marei M, Mir MA, Monagel D, Quessar A, Rihani R, Shabbir-Moosajee M, Shaheen M, Sultan AM, Vaezi M, Rondelli D, Koh MBC, Peric Z, Atsuta Y, Chaudhri N, Aljurf M
Hematol Oncol Stem Cell Ther · 2025 Apr-Jun 01 · PMID 40539439 · Publisher ↗
BACKGROUND: The treatment of acute and chronic graft-versus-host disease (GvHD) remains a challenge, particularly in cases of steroid-refractory GvHD. The management of GvHD varies between institutions, and little is kno...
BACKGROUND: The treatment of acute and chronic graft-versus-host disease (GvHD) remains a challenge, particularly in cases of steroid-refractory GvHD. The management of GvHD varies between institutions, and little is known regarding the practices in different regions of the world. Thus, the Worldwide Network for Blood and Marrow Transplantation has developed a questionnaire to understand the current practices of GvHD management in the Eastern Mediterranean (EM) region. METHODOLOGY: The questionnaire had 46 items and was distributed electronically to transplant centers in the EM region. Responses were received between December 2022 and June 2023. The questionnaire addressed the management of acute and chronic GvHD for both newly diagnosed and refractory cases. RESULTS: The questionnaire was completed by 30 programs across 26 institutions located in 11 countries. For patients with newly diagnosed acute GvHD, most programs reported the use of systemic steroids for initial treatment, with doses selected based on the severity of the presentation: the equivalent of 1 mg/kg/day of prednisone for grade IIa and 2 mg/kg/day for grade IIb. In addition to steroids, most programs continued immunosuppressive therapy or reintroduced it if GvHD developed after its cessation. For patients who were refractory to steroids, ruxolitinib was the most frequently selected second-line treatment, chosen by 80% of the programs, followed by calcineurin inhibitors (47%), high-dose steroids (>2 mg/kg, 43%), mycophenolate mofetil (MMF, 40%), and extracorporeal photopheresis (ECP, 40%). On the other hand, for patients with newly diagnosed chronic GvHD, systemic steroids are used for the initial management of mild chronic GvHD not accessible by topical treatment and moderate to severe disease, with the most commonly used initial dose being the equivalent of 0.5 to 1 and >1 mg/kg/day of prednisone, respectively. More than two-thirds of the programs use another agent in addition to steroids in patients who develop moderate/severe chronic GvHD while off immunosuppressive therapy. For patients with steroid-refractory chronic GvHD, most programs selected multiple options in the second-line setting, with the most frequently selected options being ruxolitinib (77%), calcineurin inhibitors (68%), MMF (53%), imatinib (53%), ECP (50%), rituximab (47%), and ibrutinib (40%). CONCLUSION: Our results demonstrated that GvHD management practices in the EM region generally align with current guidelines. However, the results highlight that access to clinical trials and multidisciplinary support teams remains limited.
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