Hematology Reports最新文献

{"title":"Pirtobrutinib Monotherapy for First-Line Chronic Lymphocytic Leukemia: A Non-Anchored Indirect Comparison Using Reconstructed Patient-Level Data.","authors":"Andrea Messori, Lorenzo Gasperoni, Luna Del Bono, Vera Damuzzo","doi":"10.3390/hematolrep18040058","DOIUrl":"10.3390/hematolrep18040058","url":null,"abstract":"<p><p><b>Background:</b> Pirtobrutinib has recently emerged as a promising first-line treatment option for chronic lymphocytic leukemia (CLL). Unlike currently established regimens, which are generally based on doublet combinations, pirtobrutinib can be administered as monotherapy. No head-to-head trials comparing pirtobrutinib with contemporary first-line combinations are currently available; hence, indirect comparative evidence may help define its potential role. <b>Methods:</b> A non-anchored indirect comparison based on reconstructed individual patient data (IPD) was conducted using published Kaplan-Meier curves from randomized controlled trials evaluating first-line treatments for CLL. Progression-free survival (PFS) was the endpoint of interest. Reconstructed IPD were generated using WebPlotDigitizer and the IPDfromKM algorithm. Then, Kaplan-Meier curves were plotted based on these patients, and the values of the restricted mean survival time (RMST) at 36 months were determined. Regarding PFS, pirtobrutinib monotherapy was compared indirectly with acalabrutinib plus obinutuzumab, venetoclax plus obinutuzumab, and venetoclax plus ibrutinib. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using univariate Cox models. The non-inferiority of pirtobrutinib monotherapy versus doublet regimens was assessed according to a non-inferiority margin set at HR = 1.15. Finally, the value-based prices of the new treatments were estimated based on a willingness-to-pay threshold of euro 30,000 per disease-free year gained and compared with the corresponding real prices in the Italian market. <b>Results:</b> The analysis included four randomized trials. Compared with pirtobrutinib monotherapy, HRs for PFS were 0.5544 (95%CI, 0.2696-1.1397) versus venetoclax plus obinutuzumab, 0.4583 (95%CI, 0.2066-1.0200) versus venetoclax plus ibrutinib, and 1.4453 (95%CI, 0.6684-3.1240) versus acalabrutinib plus obinutuzumab. Pirtobrutinib met the non-inferiority criterion compared with venetoclax plus obinutuzumab and venetoclax plus ibrutinib, but not with acalabrutinib plus obinutuzumab; however, these results were negatively affected by the small number of events in the pirtobrutinib arm, which generated wide CIs. In the preliminary pharmacoeconomic analysis, venetoclax plus obinutuzumab showed the most favorable profile in the comparison of value-based price vs. real price. <b>Conclusions:</b> This exploratory non-anchored analysis suggests that pirtobrutinib monotherapy may provide PFS outcomes broadly comparable to current first-line combination regimens for CLL. Given the methodological limitations inherent to indirect comparisons, prospective head-to-head studies are needed to clarify the optimal positioning of pirtobrutinib in treatment-naïve CLL.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is There Still a Role for Autologous Stem Cell Transplantation in Older Adults with AML?","authors":"Saveria Capria, Clara Minotti, Massimo Breccia, Maria Laura Bisegna, Ida Carmosino, Patrizia Chiusolo, Luca Di Marino, Giovanni Luzi, Sabrina Mariani, Giovanni Marsili, Leonardo Marabitti, Elettra Ortu La Barbera, Lorena Scollo, Maurizio Martelli, Silvia Maria Trisolini","doi":"10.3390/hematolrep18040057","DOIUrl":"10.3390/hematolrep18040057","url":null,"abstract":"<p><p><b>Introduction</b>: Autologous stem cell transplantation (ASCT) is regaining interest as a consolidation strategy for acute myeloid leukemia (AML) patients with favorable/intermediate risk and measurable residual disease (MRD) negativity. In fit older adults, its role remains debated due to concerns regarding toxicity and stem cell collection. Aim: To evaluate the long-term outcomes of ASCT in AML patients aged ≥60 years in first complete remission (CR1). <b>Methods</b>: We retrospectively analyzed 43 non-M3 AML patients (median age 64, range 60-72) who underwent ASCT in CR1 across five centers (2000-2024). Risk was stratified by ELN 2017. Primary endpoints were overall survival (OS) and disease-free survival (DFS). <b>Results</b>: The cohort included 22 favorable-risk and 21 intermediate-risk patients. Most (88%) achieved CR1 after one induction course. Median neutrophil and platelet engraftment occurred at 13 and 15 days, respectively. Grade III/IV infections were observed in 28% of patients; transplant-related mortality was low at 4%. At a median follow-up of 77 months, 5-year OS and DFS were 51% (95% CI: 37-70%) and 47% (95% CI: 34-65%), respectively. OS was significantly superior in favorable- versus intermediate-risk patients (68% vs. 35%, <i>p</i> = 0.027), with a similar trend for DFS (57% vs. 35%, <i>p</i> = 0.07). The number of consolidation cycles did not impact survival outcomes. <b>Conclusions</b>: This multicenter study confirms that ASCT is a feasible and effective consolidation strategy for selected fit AML patients aged ≥60. The low mortality and encouraging survival, particularly in favorable-risk subgroups, support ASCT as a valid alternative to prolonged chemotherapy or maintenance.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid/Lymphoid Neoplasm with FGFR1::ZMYM2 Rearrangement Presenting as T-Cell Acute Lymphoblastic Lymphoma with Concurrent Myeloproliferative Neoplasm: A Case Report.","authors":"Meha Krishnareddigari, Gopal Patel, Aqiba Bokhari, John Paul Graff, Denis M Dwyre, Arun Panigrahi","doi":"10.3390/hematolrep18040056","DOIUrl":"10.3390/hematolrep18040056","url":null,"abstract":"<p><p><b>Background:</b> Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1), also known as 8p11 myeloproliferative syndrome, are rare and aggressive hematologic malignancies arising from pluripotent stem cells. The FGFR1::ZMYM2 fusion resulting from t(8;13)(p11.2;q12) characteristically co presents as T-lymphoblastic lymphoma in lymph nodes alongside a myeloproliferative neoplasm in the bone marrow. The disease is resistant to tyrosine kinase inhibitors and conventional chemotherapy, and carries a median survival of less than 12 months without allogeneic hematopoietic stem cell transplantation (allo-HSCT). <b>Case Presentation</b>: We report a 23-year-old female who presented with progressive cervical lymphadenopathy and hyperleukocytosis (WBC 186.6 K/μL). Excisional lymph node biopsy demonstrated T-cell acute lymphoblastic lymphoma (T-ALL) with eosinophilic infiltration; immunohistochemistry confirmed lymphoblasts positive for CD1a, CD2, CD3, CD4, CD5, CD7, CD8, and TdT. Concurrent bone marrow biopsy showed a myeloproliferative neoplasm without excess blasts. Chromosomal analysis confirmed t(8;13)(p11.2;q12) with FGFR1::ZMYM2 rearrangement, and NGS identified a concurrent CSF3R variant (Q741*). She received induction chemotherapy per the PEDS AALL1231 protocol (Arm A) followed by consolidation, with a course complicated by hyperleukocytosis, venous thromboembolism, <i>E. coli</i> bacteremia, and severe mucositis requiring PICU admission. Despite initial response, the disease progressed to acute myeloid leukemia (AML) with acquisition of a PTEN variant; the patient was offered but did not complete allo-HSCT and died of refractory AML approximately 10 months after diagnosis. <b>Conclusions</b>: This case highlights the aggressive clinical course and diagnostic challenges of MLN-FGFR1, a rare stem cell-derived myeloid/lymphoid neoplasm. To our knowledge, this appears to be the first reported case documenting sequential CSF3R and PTEN variant acquisition with complete follow-up through fatal AML transformation, and the first to describe treatment with a pediatric ALL induction protocol (PEDS AALL1231) in this setting. The characteristic histomorphologic pattern of eosinophil-rich T-ALL in lymph nodes with concurrent myeloproliferative neoplasm in bone marrow should prompt immediate molecular workup. Allo-HSCT must be pursued urgently at diagnosis, as complications rapidly narrow the transplant window and the disease is uniformly fatal without it.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tympanic Membrane Involvement of Multiple Myeloma: Report of a Case.","authors":"Elisavet Manaki, Antri Polyviou, Sosana Delimpasi, Mathilde Chroni, Ioannis Vlastos","doi":"10.3390/hematolrep18040055","DOIUrl":"10.3390/hematolrep18040055","url":null,"abstract":"<p><p>Extramedullary Involvement (EMI) in Multiple Myeloma (MM) is a rare but aggressive entity that usually occurs in advanced or relapsed cases of MM. Although otologic manifestations aren't frequent, they may mimic common inflammatory or neoplastic pathologies and could be a diagnostic challenge for the clinician. Case presentation: A 65-year-old woman with a history of Relapsed Refractory Multiple Myeloma (RRMM) presented at our outpatient Otolaryngology department with a four-month history of right-sided aural fullness and a minor episode of watery otorrhea. Otoscopy revealed an abnormal tympanic membrane lesion, and audiological evaluation showed moderate conductive hearing loss. The rest of the examination was normal. A Computed Tomography (CT) scan showed a soft-tissue mass occupying the tympanic membrane with associated temporal bone erosion. The history of RRMM and otoscopic and CT findings were indicative of EMI. After multidisciplinary consultation with a hematologist and radiologist, systemic therapy for relapsed disease was initiated, with consideration of adjunctive radiotherapy. However, the clinical course of the patient deteriorated and she eventually died due to her multiple comorbidities. Conclusions: EMI of the tympanic membrane is a rare entity, among the few reported cases with otologic involvement and it remains a diagnostic \"challenge\" because it resembles many other otologic conditions. Careful analysis of imaging findings in combination with the patient's medical history is the key to accurate diagnosis. Early recognition is necessary to guide appropriate management, avoid unnecessary surgical intervention, and enable timely initiation of systemic therapy.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Teclistamab Monotherapy in Relapsed or Refractory Multiple Myeloma: A Real-World Focused Systematic Review and Meta-Analysis of Efficacy and Safety.","authors":"Jerry Qi, Daniel Park, Pranati Shah, Mojtaba Akhtari","doi":"10.3390/hematolrep18040054","DOIUrl":"10.3390/hematolrep18040054","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Teclistamab is a B-cell maturation antigen (BCMA)-directed bispecific antibody approved for relapsed or refractory multiple myeloma (RRMM). Although prior analyses have summarized teclistamab outcomes, some have included combination regimens or broader comparative studies. Given the expanding real-world experience with teclistamab, we conducted a systematic review and meta-analysis focused on teclistamab monotherapy in RRMM. <b>Methods:</b> We performed a systematic review and meta-analysis of clinical trials and retrospective real-world studies evaluating teclistamab monotherapy in RRMM. The primary endpoint was overall response rate (ORR). Secondary endpoints included complete response (CR), overall mortality rate (OMR), mortality due to multiple myeloma progression, teclistamab-attributed mortality, adverse event-related mortality, grade ≥3 cytokine release syndrome (CRS), grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS), and other grade ≥3 adverse events. Pooled proportions were estimated using random-effects models. <b>Results:</b> Twelve studies including 761 patients were analyzed, comprising two clinical trials and ten real-world retrospective cohorts. The pooled ORR was 60.9%, and the pooled CR rate was 25.2%. The pooled OMR was 26.9%, with mortality due to myeloma progression of 23.9%, adverse event-related mortality of 8.1%, and teclistamab-attributed mortality of 3.3%. Severe (grade ≥3) CRS and ICANS were uncommon, with grade ≥3 events occurring in 1.7% and 3.1%, respectively. Grade ≥3 infections occurred in 28.3%. Common grade ≥3 hematologic adverse events included lymphopenia, neutropenia, anemia, and thrombocytopenia. <b>Conclusions:</b> Teclistamab monotherapy demonstrates meaningful clinical activity and a manageable immune toxicity profile in heavily pretreated RRMM. However, severe infections and hematologic toxicities remain important clinical considerations, supporting the need for close monitoring, infection prevention, and supportive care during therapy.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminished Prognostic Value of Interim PET in Hodgkin Lymphoma Treated with Brentuximab Vedotin Plus AVD: A Retrospective Analysis.","authors":"Kareem Latif, Isaiah Courtad, Avery Stuart, Faisal Ansari, Ravand Samaeekia, Mojtaba Akhtari","doi":"10.3390/hematolrep18040053","DOIUrl":"10.3390/hematolrep18040053","url":null,"abstract":"<p><p><b>Background</b>: Interim PET after two cycles (PET2) has historically guided risk-adapted therapy in Hodgkin lymphoma (HL). Its value with frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) is uncertain, as BV + AVD improves progression-free survival and may reduce the prognostic relevance of early metabolic response. Our aim was to assess whether PET2 retains prognostic utility in HL patients treated with BV + AVD. <b>Methods</b>: We retrospectively reviewed 55 newly diagnosed classical HL patients treated with frontline BV + AVD. The primary endpoint was PET2 performance for predicting EOT PET positivity. Sensitivity, specificity, predictive values, and likelihood ratios were calculated with 95% confidence intervals. <b>Results</b>: Median age was 22 years (range 11-77), 49% were male, and 73% had stage III-IV disease. PET2 was negative in 51 patients (92.7%) and positive in 4 (7.3%). EOT PET was negative in 48 (87.3%) and positive in 7 (12.7%). Of seven EOT PET-positive patients, three were PET2-positive and four PET2-negative. Of 48 EOT PET-negative patients, 47 were PET2-negative and 1 PET2-positive. PET2 sensitivity was 42.9%, specificity 97.9%, positive predictive value 75.0%, and negative predictive value 92.2%. Positive likelihood ratio was 20.6; negative likelihood ratio was 0.58. <b>Conclusions</b>: In HL patients treated with BV + AVD, most achieve PET2 negativity, limiting interim PET discrimination. Negative PET2 adds little reassurance beyond the high baseline success rate, while positive PET2 is uncommon and identifies only a subset of eventual treatment failures. These findings question the routine use of PET2 to guide therapy in the BV + AVD era.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with Increased Healthcare Utilization Within 30 and 90 Days Post-Discharge of CAR-T Cell Therapy in Patients with R/R LBCL.","authors":"Philip Yeung, Aaron Trando, Ah-Reum Jeong, Dimitrios Tzachanis","doi":"10.3390/hematolrep18040052","DOIUrl":"10.3390/hematolrep18040052","url":null,"abstract":"<p><p><b>Background/Objectives</b>: CAR T-cell therapy is a highly efficacious therapy option for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), but its widespread use is currently limited by safety concerns and high healthcare costs. <b>Methods</b>: We evaluated 66 patients with R/R LBCL treated with tisagenlecleucel or axicabtagene ciloleucel between 2016 and 2022 at a single institution to identify factors associated with increased healthcare utilization. <b>Results</b>: The median age of our cohort was 59.5 years, with 22.7% over the age of 70. The median length of stay (LOS) during the initial hospitalization was 12 days (range, 7-62 days). Longer initial hospital LOS was linked to higher age-adjusted HCT-CI score (IRR 1.08; 95% CI, 1.01 to 1.15; <i>p</i> = 0.0203), thrombocytopenia grade 3-4 (IRR 1.32; 95% CI, 1.07 to 1.63; <i>p</i> = 0.0091), and first ICU admission (IRR 1.81; 95% CI, 1.37 to 2.38; <i>p</i> < 0.00001). Thirty- and 90-day readmission rates post-discharge after receiving CAR T-cell therapy were 21.2% and 28.8%, respectively. Multiple readmissions within 90 days after initial hospital discharge were observed in 15% of patients. Longer 30-day readmission LOS was linked to initial hospital LOS (IRR 1.23; 95% CI, 1.11 to 1.35; <i>p</i> < 0.0001) but outpatient follow-up was associated with shorter 30-day readmission LOS (IRR 0.43; 95% CI, 0.26-0.69; <i>p</i> = 0.0005). Factors associated with longer 90-day readmission LOS included a greater number of ER visits within 60 days of CAR T-cell therapy (IRR 3.10; 95% CI, 2.15-4.46), prior 30-day readmission LOS (IRR 1.35; 95% CI, 1.14-1.60), and SUVmax at Day 30 (IRR 1.06; 95% CI, 1.03-1.09) (all <i>p</i>-values < 0.0001). <b>Conclusions</b>: Our findings identify key clinical and utilization variables associated with initial and repeat hospitalizations post-CAR T-cell therapy, emphasizing the need for targeted interventions to reduce readmissions and optimize post-discharge care.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexities in the Diagnostic Evaluation and Treatment of Infant Hemophagocytic Lymphohistiocytosis.","authors":"Reeja Raj, Ramya Ramakrishnan, Carlos Vargas, Muhammad Khalid, Gopi Mohan, David McCall, Amber Gibson, Branko Cuglievan, Cesar Nunez, Brandon Brown, Monica Bray, Miriam B Garcia","doi":"10.3390/hematolrep18040051","DOIUrl":"10.3390/hematolrep18040051","url":null,"abstract":"<p><p>Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of the immune system. Case Presentation: We present the case of an eight-month-old infant with influenza A(H1N1) who presented with seizures, hepatosplenomegaly, cytopenias, and markedly elevated levels of ferritin, IL-18, and CXCL9, raising concern for HLH. Despite initiation of HLH-directed and antiviral therapy, she succumbed to cardiorespiratory failure. Genetic testing revealed heterozygous variants in <i>LYST</i> and <i>NLRC4,</i> suggesting a potential genetic predisposition. Conclusions: This case underscores the challenge of distinguishing primary from secondary HLH and highlights the importance of balancing aggressive immunosuppression with infection control. Early genetic and cytokine profiling may assist in guiding personalized treatment strategies, enabling targeted interventions that avoid excessive immunosuppressive treatment in cases of reactive hyperinflammation while facilitating timely escalation of therapy in true or refractory HLH.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surrogate Endpoints in CLL: From Promise and Pitfalls to a Context-Specific Validation Framework.","authors":"Stefano Molica","doi":"10.3390/hematolrep18040050","DOIUrl":"10.3390/hematolrep18040050","url":null,"abstract":"<p><p>Surrogate endpoints are increasingly used in chronic lymphocytic leukemia (CLL) to accelerate treatment evaluation, but their validity is context-dependent. This review examines key endpoints-progression-free survival (PFS), time to next treatment (TTNT), measurable residual disease (MRD), and quality of life (QoL)/patient-reported outcomes (PROs). PFS, while standard, is limited by competing risks and poor reflection of toxicity and patient experience. TTNT captures both efficacy and tolerability but is influenced by external factors. MRD is a strong predictor of outcomes in fixed-duration venetoclax-based regimens but less reliable in continuous therapies. QoL and PROs provide essential patient-centered insight often missed by traditional endpoints. We propose a practical framework in which endpoint selection depends on treatment type, patient characteristics, and intended use. MRD is most informative after fixed-duration therapy, TTNT in continuous treatment, and PROs in vulnerable populations. Overall, surrogate endpoints in CLL require setting-specific validation to ensure they reflect meaningful clinical benefit.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Spectrum and Differential Diagnosis of Adult Thrombotic Microangiopathies: Real-World Experience from a Tertiary Referral Center.","authors":"Nazlı Pelin Kırkayak, Gulsum Ozet, Simten Dagdas, Funda Ceran, Ihsan Ates","doi":"10.3390/hematolrep18040049","DOIUrl":"10.3390/hematolrep18040049","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Thrombotic microangiopathies are rare, life-threatening hematological disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury. This study was conducted in a setting where ADAMTS13 activity testing became available only from 2015 onward and complement-targeted therapy (eculizumab) had limited accessibility throughout most of the study period, conditions that shaped both diagnostic classification and treatment outcomes. Their clinical presentation, treatment response, and prognosis vary according to etiology, making early recognition and subtype classification clinically important. This study aimed to evaluate the etiological distribution, clinical features, treatment responses, and outcomes of adult patients with thrombotic microangiopathy at a tertiary-center real-world cohort. <b>Methods:</b> This retrospective cohort study included 47 adult patients (≥18 years) hospitalized with thrombocytopenia and microangiopathic hemolytic anemia (MAHA) in a nine-year period. Patients were classified as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or secondary TMA based on clinical and laboratory evaluation. Demographic characteristics, clinical manifestations, laboratory parameters, treatments, and outcomes were analyzed. <b>Results:</b> The mean age was 45.3 ± 15.2 years, and 72.3% of patients were female. Primary thrombotic microangiopathy accounted for 74.5% of cases, including thrombotic thrombocytopenic purpura in 53.2% and hemolytic uremic syndrome in 21.2%; secondary thrombotic microangiopathy accounted for 25.5%. Hemodialysis was required in all patients with hemolytic uremic syndrome compared with 16% of those with thrombotic thrombocytopenic purpura. The complete response rate was 74.5%, and in-hospital mortality was 25.5%. In multivariable Cox regression analysis, treatment non-response and reduced post-treatment estimated glomerular filtration rate independently predicted mortality. <b>Conclusions:</b> Adult TMAs are characterized by considerable etiological and clinical heterogeneity, which makes differential diagnosis challenging, particularly in settings where access to contemporary diagnostic tests and targeted treatments is limited. In this cohort, in the absence of ADAMTS13 testing, TTP was the most frequent subtype, while treatment non-response and renal impairment emerged as the main factors associated with mortality. These findings emphasize the need for early clinical recognition and careful subtype-based differential diagnosis, which will reduce morbidity and mortality by permitting rapid initiation of pathophysiology-based appropriate interventions, i.e., PEx, immune suppression and caplacizumab for immune TTP and anti-complement therapy for aHUS, and limiting the inappropriate use of PEx with its complications, including sepsis.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}