Leukemia & Lymphoma最新文献

Most patients with large B-cell lymphoma (LBCL) are cured with frontline chemoimmunotherapy; however, 30-40% experience relapsed or refractory (R/R) disease. Historically, salvage chemotherapy followed by autologous stem cell transplantation (ASCT) represented the standard second-line treatment. Several studies have demonstrated that patients with primary refractory or early-relapsed LBCL derive limited benefit from ASCT. With the advent of chimeric antigen receptor (CAR) T-cell therapy, the prognosis of R/R LBCL has changed substantially. The TRANSFORM and ZUMA-7 trials, which showed superior efficacy and manageable toxicity, led to the approval of lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) as second-line options. Importantly, these trials required participants to be medically fit for ASCT. This review focuses on therapeutic options for transplant-ineligible patients with R/R LBCL. The phase II PILOT study demonstrated that liso-cel is effective in medically unfit individuals, supporting the definition of a distinct category of ASCT-ineligible patients. Additional active options include antibody-drug conjugates, bispecific antibodies in combination with chemotherapy, and other novel immunotherapies, which have shown promising response rates in this difficult-to-treat population.

Myelodysplastic neoplasms (MDS) are heterogeneous clonal disorders with increased risk of transformation to acute myeloid leukemia. The HMGA2 gene, a chromatin-binding regulator suppressed by the let-7 miRNA family, has been implicated in malignant transformation and fibrosis. In this study, HMGA2 was investigated in patients with MDS, while four members of the let-7 family (let-7a, let-7b, let-7c, let-7d) were specifically assessed in those with bone marrow fibrosis. HMGA2 showed no association with established prognostic scores or survival, while in MDS with bone marrow fibrosis, distinct let-7 patterns emerged: let-7a associated with cytopenias and reduced platelet counts, let-7c with blast percentage and ineffective hematopoiesis, while let-7d displayed a potentially protective profile with higher platelet count and fewer cytopenias. A novel positive correlation between HMGA2 and let-7d was also identified. These findings suggest that let-7 miRNAs may serve as prognostic biomarkers and therapeutic targets in fibrotic MDS, whereas HMGA2 appears less predictive.

Lymphoid cancers of different types and subtypes are known to cluster in families. We hypothesize that there are shared susceptibility factors in families with these heterogenous lymphoid malignancies. Exome sequencing was performed on 100 individuals from 43 lymphoid cancer pedigrees. Variants from 37 families were ranked using the Weights-based vAriant Ranking in Pedigrees (WARP) pipeline. Six affected unrelated probands were used for interpretation only. We detected recurrent variants in the germline lymphoid cancer gene FAM160A1 in 4 (9%) of the 43 families, and variants in other genes involved in lymphoid cancers: NPAT, BCL9, HCLS1 and ID3. Variants in genes including BCL9, LEF1, TLE3, and KLHL12 involved in the WNT/β-catenin pathway were identified, representing a novel observation. Some variants appeared to segregate with specific types of lymphoid cancers; others were shared across different subtypes. Identifying factors predisposing to different types of lymphoid cancers will help understand the etiology of these neoplasms.

Use of dietary and herbal supplements (DHS) is common among patients with chronic lymphocytic leukemia (CLL), but data in the era of targeted therapies are limited. We conducted a national prospective survey of Hebrew-speaking adults with CLL in Israel (2025), assessing DHS prevalence, patterns of use, sources of recommendation, reporting to hematologists, and patient expectations. Multivariate logistic regression identified factors associated with DHS use. Among 267 respondents, 49% reported current or past DHS use. Use was independently associated with female gender and residence in Central Israel. Most DHS were used for general or 'immune' strengthening, with high perceived effectiveness. Hematologists were the main advisors for 42% of DHS use, and 65% of patients disclosed DHS use to their physician. DHS use is common among patients with CLL and involves relatively high patient-hematologist communication, underscoring the need for evidence-based integrative counseling.

In a Norwegian national cross-sectional survey, we assessed the burden of selected late effects (LEs) by a 95-item questionnaire in tumor-free Hodgkin lymphoma survivors (HLSs) diagnosed at age ≥60 years. Responses were compared to age- and sex-matched controls. A total of 290 older HLSs diagnosed 2000-2021 received the questionnaire, 193 (67%) were included. Median age at survey was 76 years (range 63-92) and median time since diagnosis 7 years (2-23). Compared to controls, HLSs reported significantly higher rates of heart failure (10% vs. 6%), atrial fibrillation (19% vs. 14%), memory problems (48% vs. 37%), other cognitive difficulties (34% vs. 17%) and chronic fatigue (29% vs. 13%). HLSs scored lower on physical and mental health-related quality of life (HRQoL) and more often reported needing help with basic (P-ADL) and instrumental activities of daily living (I-ADL). However, differences were small, only for fatigue and dependence in I-ADL did the difference reach moderate statistical effect size.

t(14;19)(q32;q13) is found in a fraction of chronic lymphocytic leukemia (CLL) patients and creates the IGH::BCL3 fusion gene, but this translocation has been observed in B-cell lymphomas other than CLL (non-CLL BLs). Ultra-high molecular weight DNA from liquid nitrogen-frozen leukemia cells of one CLL patient and OCT compound-embedded cryopreserved biopsies from two non-CLL BL patients, all of whom carried cytogenetic t(14;19), were subjected to optical genome mapping. In the CLL patient, t(14;19) resulted in fusion between IGHA1 and BCL3, whereas in the non-CLL BL patients, breakpoints on 19q13.32 involved NECTIN2 and BCAM as the IGH partners, both of which were located telomeric to BCL3. On der(19)t(14;19), chromosome 19 sequences centromeric to the breakpoints were fused to the germline IGHVs, or IGHV-D-J rearrangement sequences followed by the 5' Eµ enhancer and IGHM/IGHD constant genes. In the non-CLL BL patients, BCL3 was retained on der(19)t(14;19) and potentially affected by the translocated IGH.