Hematological Oncology最新文献

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18^th edition of the workshop and includes reference to some data presented or published after the workshop, including the 26^th John Goldman CML conference.

Disease burden is a critical determinant of outcomes in CAR-T therapy for B-cell lymphomas, and one of the most widely used techniques for its assessment is Total Metabolic Tumor Volume (TMTV) measured via [¹⁸F]FDG PET/CT. Biological parameters may further refine the risk profile. We analyzed baseline [¹⁸F]FDG PET/CT scans from 40 patients treated with CAR-T, using an AI-based automated segmentation algorithm to determine TMTV. Our analysis identified that a baseline TMTV greater than 48.4 cm³ and elevated LDH independently predicted progression-free survival (PFS) after CAR-T therapy (HR 4.28, p = 0.007, and HR 8.20, p < 0.001, respectively). We then proposed a 0-to-2 risk score, assigning one point each for elevated TMTV and elevated LDH. All patients with a score of two experienced a PFS of less than 90 days following CAR-T infusion. Among the remaining patients, those with 0 points versus 1 point demonstrated a 3-month PFS of 100% versus 85%, a 6-month PFS of 92% versus 53%, and a 12-month PFS of 83% versus 53%, respectively. Importantly, patients with high baseline TMTV who achieved a TMTV reduction to less than 1.99 cm³ by day 30 had a PFS of 66%, significantly better compared to those who did not achieve this reduction. AI-guided TMTV assessment, combined with LDH levels, provides a rapid and sensitive method for risk stratification at the bedside, which could help optimize patient management prior to CAR-T therapy.

Anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma (ALCL) typically affects young individuals and, despite high responsiveness to cytotoxic drugs, relapses occur in over 50% of patients. Crizotinib has improved outcomes, but its management in patients desiring parenthood remains an issue. This study presents the first description of four successful pregnancies during crizotinib treatment for ALK+ALCL: a female patient achieving two pregnancies through assisted reproductive technologies (ART), temporarily discontinuing crizotinib and maintaining a complete remission (CR), and a male patient conceiving naturally while on continuous therapy. These cases demonstrate crizotinib potential to support conception without compromising disease control, even in the absence of specific guidelines on treatment discontinuation.

Newly diagnosed follicular lymphoma (FL) patients usually received first-line rituximab-based immunochemotherapy (R-chemo). Recently, rituximab plus lenalidomide (R2) emerged as an alternative chemo-free immunotherapy. We performed a comparative analysis of positron emission tomography/computed tomography (PET/CT) in FL undergoing R-chemo or R2. With data of sequential PET/CT at the baseline, interim, and end-of-induction, treatment responses and survival outcomes were analyzed using Deauville scores at the interim and end-of-induction. Additionally, correlations between interim Deauville scores and baseline PET/CT parameters were explored. Conclusively, we revealed that Deauville 1-3 at the interim and end-of-induction showed lower disease progression within 24 months (POD24) and superior progression-free survival (PFS) in R-chemo and R2 cohorts. Also, patients with interim Deauville 1-3 exhibited reduced POD24 and favorable PFS as compared to those with interim Deauville 4-5/end-of-induction Deauville 1-3. Furthermore, total lesion glycolysis of baseline PET-CT surpassed standardized uptake value and total metabolic tumor volume in predicting interim Deauville 1-3, with different optimal cutoffs of 2600 and 600 mL in the R-chemo and R2 cohort. These findings underscored the potential of PET-CT-adapted strategies to achieve durable remission in FL undergoing rituximab-based immunochemotherapy or immunotherapy.

Various prognostic scoring systems in myelofibrosis (MF) have been developed to guide clinical decision-making in MF. However, discrepancies between different scoring systems for individual patients remain poorly understood, which can result in conflicting treatment recommendations. Moreover, data regarding there applicability in Asian populations remain scarce. We conducted a retrospective analysis of patients with overt MF at National Taiwan University Hospital from November 1, 2006, to November 30, 2023. This study evaluates the distribution, concordance, and prognostic value of various scoring systems (IPSS, DIPSS, DIPSS+, MYSEC-PM, MIPSS70, MIPSS70+v2, GIPSS), focusing on the mutational landscape, particularly TP53 mutations, and cytopenic phenotypes in an Asian MF cohort. All prognostic systems effectively stratified patients by risk (p < 0.005); however, concordance between systems was low (Cohen's κ < 0.4, except for IPSS vs. DIPSS+). GIPSS demonstrated superior performance with a comparable C-index but lower Akaike and Bayesian information criterion values. Besides high-molecular risk mutations, TP53 mutations (5.2%) were associated with worse overall survival (OS) (5-year: 30% vs. 68%, p < 0.001) and a trend toward higher leukemic transformation (5-year: 22% vs. 10%, p = 0.055). Cytopenic phenotype (59%) was associated with a higher incidence of ASXL1 mutations (44% vs. 28%, p = 0.04). In multivariable analysis, elderly patients, higher-risk GIPSS, TP53 mutation and cytopenic phenotype were associated with a poorer OS. This study validated multiple prognostic scoring systems in an Asian MF cohort, with GIPSS showing superior risk stratification. Further, cytopenic phenotype and TP53 mutations were identified as independent factors linked to poorer survival.

POEMS syndrome is a multisystemic disease associated with monoclonal plasma cell disorders. Although the presence of bone lesions is included in the diagnostic criteria, their precise manifestations remain unknown. Here, we retrospectively analyzed the bone lesions in patients with POEMS syndrome and evaluated their clinical features. Clinical data and bone lesion information by computed tomography (CT) imaging were obtained from the 114 patients with POEMS syndrome. Regardless of the presence of sclerotic bone lesions, patients were divided into two groups according to the presence (lytic group: n = 17, 14.9%) or absence (non-lytic group: n = 97, 85.1%) of osteolytic lesions. In the lytic group, several patients were histologically diagnosed with plasmacytoma. In the evaluation by CT imaging, osteolytic lesions had a higher response rate than sclerotic lesions (75.0% vs. 42.2%, p = 0.079). Nevertheless, patients in lytic group showed earlier clinical progression than patients in non-lytic group (2-year progression-free survival, 66.7% vs. 90.2%, p = 0.069). The presence of innumerable bone lesions was an independent poor prognostic factor in multivariate analysis, regardless of the presence of osteolytic lesions (hazard ratio, 3.4; 95% confidence interval 1.1-10.9; p = 0.040). Osteolytic and innumerable bone lesions are potential prognostic factors. Further studies involving histopathological evaluations of bone lesions are warranted.