Expert Review of Hematology最新文献

Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative disorder, usually diagnosed in its chronic phase (CP), often requiring life-long therapy. Despite the effectiveness of targeted therapy with tyrosine kinase inhibitors (TKIs), resistance or intolerance may occur, requiring a switch. The probability of achieving guideline-recommended cytogenetic and molecular responses declines from first (1 L) to second (2 L) and subsequent lines. About half of the patients receiving third line TKI treatment exhibit resistance or intolerance to prior TKIs. Post-2 L, patients experience non-durable responses, persistent adverse events, and a decreased quality of life.

Areas covered: This narrative review is based on targeted literature search in Medline via PubMed and expert clinical input from Indian hematologists to cover unmet needs of patients with CP-CML post-2 L of TKI therapy. We present an overview of the available clinical data, outline the challenges associated with treatment resistance and intolerance, identify gaps in patient management, and discuss personalized treatment approaches that could bridge these gaps and improve patient outcomes post-2 L.

Expert opinion: Management of CP-CML beyond 2 L remains a significant clinical challenge due to resistance, intolerance, and suboptimal long-term responses with currently available TKIs. Integrating newer agents like asciminib or ponatinib, can help overcome resistance and improve patient outcomes.

Background: Inherited bone marrow failure syndromes (IBMFS) often present with overlapping features and may be misdiagnosed as idiopathic aplastic anemia (iAA). Genetic testing is critical for accurate diagnosis, especially in consanguineous populations.

Research design and methods: We retrospectively analyzed 41 pediatric patients who underwent genetic evaluation for suspected bone marrow failure. Clinical features, diagnostic classifications, and genetic findings were reviewed to assess diagnostic yield and impact.

Results: The cohort included 21 males and 20 females (median age: 8 years). Pancytopenia was the most common presentation (27/41; 65%), half (20/41; 49%) were products of consanguineous marriage. iAA was the initial diagnosis in 56% (23/41). Genetic testing identified pathogenic/likely pathogenic (P/LP) variants in 14 patients (34%), enabling a molecular diagnosis. An additional 13 patients (32%) had variants of uncertain significance, one of which was later reclassified as LP, confirming Noonan syndrome. Genetic findings prompted diagnostic revisions, including Fanconi anemia, Congenital Amegakaryocytic Thrombocytopenia, Shwachman-Diamond syndrome, and Diamond-Blackfan anemia. Commonly affected genes included MPL, FANCA, followed by DANJC21.

Conclusions: In this Pakistani cohort, genetic testing clarified IBMFS diagnoses in 34% of cases, matching global yields. It enhanced diagnostic precision, informed management, and supported family counseling, though high VUS rates underscore the need for ongoing reclassification and multidisciplinary care.

Background: The diagnostic and prognostic value of the systemic immune inflammation (SII) index for immune thrombocytopenia (ITP) remains to be determined.

Research design and methods: A retrospective analysis was conducted on 120 ITP children admitted to The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital) between January 2017 and June 2022. A control group comprised 79 healthy children undergoing outpatient physical examinations during the same period. Based on recurrence within 2 years post-treatment, ITP children were categorized into recurrence and non-recurrence groups. Multivariate Cox regression analysis was conducted, and receiver operating characteristic curves and Kaplan-Meier curves were plotted.

Results: ITP children exhibited significantly reduced SII. The SII index assisted in predicting ITP occurrence and recurrence within 2 years post-treatment. PLT count and SII were independent protective factors against disease recurrence within 2 years post-treatment in ITP patients. A decrease in SII increased the risk of disease recurrence within 2 years.

Conclusions: ITP children exhibit reduced SII index. The SII index can assist in the diagnosis of ITP and demonstrates strong predictive value for disease recurrence risk within 2 years post-treatment in ITP children.

Introduction: Waldenström's Macroglobulinemia is a rare chronic, incurable low-grade lymphoma with an increasing number of targeted agents available. Selecting efficacious treatment may reduce adverse events related to inadequate responses.

Areas covered: This review focusses on therapies in WM and management of adverse events. The role of genetic alterations (MYD88, CXCR4, TP53) and prognostic scores are discussed. Data pertaining to efficacy and adverse events are described alongside investigation for IgM-associated disorders.

Expert opinion: Apparent treatment-emergent adverse events require particular attention, as these may be a manifestation of an IgM-associated disorder particularly systemic AL amyloidosis, IgM associated neuropathy or disease progression. Treatment 'failure' may be through resistance or dose-limiting toxicities. Post Bruton's tyrosine kinase inhibitors, novel therapies and combinations are being investigated. Ongoing work on issues of quality of life and patient reported outcomes will better inform our understanding of patient experience and should be reported in clinical trials.

Introduction: Myelofibrosis is a clonal myeloproliferative neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, progressive cytopenias, and systemic symptoms, with risk of leukemic transformation. Advances in understanding its molecular pathogenesis, particularly JAK-STAT signaling, have reshaped treatment approaches, though allogeneic transplantation remains the only potential cure.

Areas covered: We review current diagnostic frameworks, prognostic models, and treatment strategies, including approved JAK inhibitors and emerging investigational therapies. Literature was identified through PubMed searches and relevant conference proceedings, with emphasis on pivotal clinical trials, novel targeted agents, and evolving management of cytopenias and advanced disease.

Expert opinion: It is an exciting time in myelofibrosis research. Investigation into the molecular underpinnings of the disease and elucidation of many key pathways beyond JAK-STAT signaling have led to a profusion of new drug classes entering the clinic. The results of several, potentially paradigm-shifting key phase 3 trials are eagerly awaited. While JAK inhibitors remain the only approved agents, this could soon change. Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.

Introduction: Renal impairment (RI), defined as a creatinine clearance of < 40 mL/min, affects up to half of patients with multiple myeloma (MM). Patients with MM and RI historically had poorer outcomes, likely due to the limited access to novel treatments available through clinical trials. Strict eligibility criteria for MM clinical trials often exclude patients with RI, necessitating reliance on patient data acquired from real-world (RW) clinical practice to guide therapeutic decisions. Therefore, there is a need for RW data and expert recommendations to guide treatment strategies for patients with MM and RI.

Areas covered: Teclistamab treatment and pharmacokinetics in patients with mild-to-moderate RI, including the first report of a RI patient subgroup from the MajesTEC-1 study, as well as published RW experiences of teclistamab, primarily in patients with moderate-to-severe RI.

Expert opinion: Current guidelines, available data, and our clinical experience broadly support the feasibility and potential benefit of teclistamab for patients with MM and RI, including those on dialysis, providing appropriate precautions are taken. This expert opinion offers recommendations for optimizing the management of patients with MM and RI treated with teclistamab. Additional RW data will further inform the safety and efficacy profile of teclistamab in this patient population.

Background: Sickle cell disease (SCD) is a common inherited blood disorder causing high maternal and fetal morbidity during pregnancy. Hydroxyurea (HU) is a standard SCD therapy, but its safety in pregnancy remains uncertain due to concerns about congenital anomalies. This study evaluates maternal-fetal outcomes in pregnant women with SCD who received HU versus those who did not.

Research design and methods: A retrospective review was conducted at Kasturba Hospital, Gujarat, India. Pregnant women with SCD who received HU were compared with a historic control group. Maternal morbidities, fetal outcomes, and congenital anomalies were assessed. Poisson regression was done.

Results: Among a total of 235 pregnant women with SCD, 154 received HU (440.5 person-months), while 81 did not (269.6 person-months). The HU group had a lower adverse maternal event score (91.2 vs. 109.8 per 100 person-months, adjusted IRR 0.82, 95% CI 0.71-0.96, p = 0.01) and reduced maternal morbidity, blood transfusion needs, complications, and deaths. No significant increase in congenital anomalies was observed. Fetal-outcomes, including live-birth, stillbirth, low birth weight, and prematurity, were comparable between groups, with no statistically significant differences.

Conclusions: HU use in pregnancy lowered maternal morbidity without increasing congenital anomalies. Further prospective studies are needed in resource-limited settings.

Introduction: Acute myeloid leukemia (AML) is a malignant clonal hematopoietic cell disorder, characterized by impaired hematopoiesis and bone marrow failure. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an established therapy with curative potential. Post-transplant relapse does occur and has dismal prognosis, which is the main cause of death after allo-HCT. Relapses after allo-HCT in AML do cause standard treatment approaches challenging, which often necessitate individualized treatment modalities and large prospective clinical trials are needed to delineate standardized therapies. The management of AML relapse after allo-HCT remains a clinical challenge, and no standardized treatment approach currently exists.

Areas covered: This review provides an overview of the available therapeutic options for patients with relapsed AML after allo-HCT. It provides a beneficial framework on the optimal treatment approach, including factors that influence drug preferences. A search of papers published up to March 2025 was conducted on PubMed using the keywords.

Expert opinion: Combining chemotherapy, targeted agents, and immunotherapy can increase the rate of response and survival for relapsed AML after allo-HCT. Future research is needed to develop strategies that can reduce the risk of relapse after allo-HCT. Individualization of treatments and exploration of combination therapies are potential approaches for improving efficacy.