Leukemia & Lymphoma最新文献

Over the past two decades, new agents for multiple myeloma (MM) have significantly improved patient outcomes, particularly for those with standard-risk disease, who now have a median overall survival of over a decade. However, this benefit is less pronounced in high-risk and ultra-high-risk MM, where median survival ranges from 3 to 5 years. The definition of HRMM continues to evolve and is driven by the genomic features, disease burden, and medical comorbidities. Various risk stratification tools are available to gauge the risk status of the disease. Recently, a slew of single-arm phase 2 trials for high-risk MM have been reported with a general theme of intensification of various phases of treatment. Additionally, minimal residual disease testing in treatment escalation/de-escalation is being actively investigated. This review summarizes the existing evidence for risk-adapted treatment in patients with MM.

Despite increasing utilization of CAR T-cell therapy, data are lacking regarding long term follow up and risk of infectious complications after the early period following CAR T-cell infusion. In this study, we sought to compare epidemiology and risk factors for early (≤ 3 months) and late (3 months to 1 year) infections. Data were retrospectively collected at six time points: pre-CAR T, day of infusion, and at 3, 6, 9, and 12 months post CAR-T infusion for all consecutive adult patients treated at our institution. In this cohort, the cumulative incidence of any infection was 73.2% in the first year. Bridging therapy, CRS, neurotoxicity and steroid use were identified as contributing risk factors for early bacterial infections. After 3 months, community acquired respiratory infections were common. We characterize bacterial, viral and fungal pathogens based on time elapsed after CAR T-cell infusion.

The diagnosis of myeloid neoplasms with plasmacytoid dendritic cell (pDC) differentiation can be challenging due to immunophenotypic overlap requiring detailed characterization by flow cytometry and immunohistochemistry. We describe two patients with a history of myeloproliferative neoplasm (MPN) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) who presented years later with leukocytosis, lymphadenopathy, splenomegaly, and cachexia, with rapid clinical deterioration and death. Lymph node biopsy specimens revealed involvement by myeloid sarcoma with prominent pDC differentiation. Furthermore, concomitant bone marrow aspiration and biopsy showed involvement by the underlying myeloid neoplasm but no parallel expansion of pDC, as seen in the lymph node specimens, suggesting that pDC differentiation is fostered in the lymph node microenvironment. These two cases could represent the "myeloid sarcoma" counterpart of the recently described acute myeloid leukemia with pDC differentiation (pDC-AML). Although patients with pDC-AML have an inferior outcome when treated with conventional therapies, the recognition of a pDC component in these neoplasms potentially expands the therapeutic options.

Chimeric antigen receptor (CAR) T-cell therapy has changed treatment landscape of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and more older patients have been treated with curative intent for R/R disease, including patients previously deemed unfit for autologous stem-cell transplant with a broader application of CAR T-cell therapy. Due to the unique CAR T-cell-related toxicity and special attention needed in treating older patients, optimal patient selection and management of CAR T-cell therapy in older patients are becoming more critical. More data are emerging in the field; multiple approaches, such as geriatric and frailty assessment and multi-disciplinary work with geriatrics, are being studied for CAR T-cell therapy application. Studies support the safe use of CAR T-cell therapy in older patients, however, application of geriatric assessment tools and maximizing multi-disciplinary approach to tailor supportive care are critical to reduce morbidity and improve outcomes in older patients.

In this multicenter phase Ib trial, we investigated the combination of CPX-351 and gemtuzumab ozogamicin (GO) in relapsed/refractory acute myeloid leukemia (AML). Cohort A received CPX-351 plus a single dose of GO, while cohort B received two doses of GO. Thirteen participants received investigational treatment. Dose-limiting toxicities (DLTs) occurred in one participant in each cohort, with manageable adverse events. No cases of hepatic sinusoidal obstructive syndrome occurred. Out of 12 evaluable participants, four achieved complete remission (CR), three of whom were negative for measurable residual disease. The median time to recovery of hematopoiesis for responders was 37 days. CPX-351 with GO was feasible with acceptable toxicity and marrow recovery kinetics. Further evaluation in a larger patient cohort is necessary to assess the efficacy of this regimen in relapsed/refractory AML.

Dual productive B-cell receptor (BCR) rearrangements have been repeatedly reported for chronic lymphocytic leukemia (CLL), but the standard population-based PCR analyses cannot distinguish whether these are bi-clonal CLL, or a monoclonal CLL with bi-allelic productive rearrangements. We investigated CLL cells by combined single-cell RNA and BCR sequencing. We identified two CLL clones using different immunoglobulin (Ig) heavy-chain V region genes (IGHV) genes and distinct Ig λ light chains. One clone is classified as Ig unmutated the other as mutated. The two CLL clones have distinct transcriptomes: Numerous genes were differentially expressed, with genes typical for unmutated or mutated CLL showing the expected representation in the two clones. Using PCR, cloning and Sanger sequencing of the IGHV rearrangements we detected both CLL clones over a period of three years without clinical progression of the CLL and thus giving insights into the disease biology of multi-clonal CLL.