Leukemia & Lymphoma最新文献

Mantle cell lymphoma (MCL) is a rare, incurable B-cell non-Hodgkin lymphoma and over half of patients affected are older adults (≥65 years of age). New targeted treatments for MCL have emerged over the past two decades. Nonetheless, MCL-specific death rates for older adults remain elevated compared with younger adults, demonstrating the challenge of treating this population. The older adult population is at risk for overtreatment or undertreatment. Clinicians must be mindful of how to optimize the holistic care of older adults receiving treatment for MCL. Evaluating fitness through a geriatric assessment (GA) is an important step when choosing therapy. The treatment armamentarium includes both chemotherapy and non-chemotherapy options and toxicities must be considered in the context of the patient's GA and proactively managed. Herein, the treatment of MCL in older adults is reviewed and strategies for choosing treatment are offered to assist in treatment decision-making for this challenging population.

Allogeneic stem cell transplantation (alloSCT) represents a curative option for patients with relapsed/refractory (r/r) aggressive lymphomas. We compared outcomes of alloSCT in r/r PTCL and r/r DLBCL pts (n = 150) who underwent identical myeloablative conditioning chemotherapy, GvHD prophylaxis, and relapse management. 5-year PFS and OS were significantly superior in PTCL compared to DLBCL (56% vs. 24%; 56% vs. 28%; p ≤ 0.005). A landmark analysis (day≥ +100 post-alloSCT) markedly favored outcomes in PTCL vs. DLBCL: 5-year PFS and OS of 76% vs. 30% and 76% and 35%, respectively (p ≤ 0.003). Non-relapse mortality was comparable (35% PTCL vs. 34% DLBCL, p = 0.894), whereas post-alloSCT relapse mortality was significantly higher in DLBCL (36% vs. 10%, p = 0.0007). The occurence of limited chronic GvHD did not improve outcomes in DLBCL, whereas extensive chronic GvHD was a negative risk factor for both (HR 2.09 and 2.80, p ≤ 0.006). In conclusion, we gained evidence for strong graft-versus-lymphoma activity against PTCL but not DLBCL.

In recent times, the application of CAR-T cell treatment has significantly progressed, showing auspicious treatment outcomes in hematologic malignancies. However, along with these advances, certain limitations and challenges hurdle the widespread utilization of this technology. Recently, CAR-NK cells have gained attention in cancer treatment, as this approach has an important advantage over CART therapy (i.e. no need for HLA matching) for targeting foreign cells. This review aims to explore the benefits of CAR NK cell therapy, and generation strategies, as well as the challenges and limitations hindering the application of CAR NK cells in experimental studies and trials on hematologic malignancies.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome characterized by uncontrolled immune activation. While traditionally associated with genetic mutations affecting cytotoxic function, recent advances have highlighted the prevalence and significance of HLH in adults, particularly in hematologic malignancies. This review focuses on malignancy-associated HLH (M-HLH), a complex and challenging condition with a poor prognosis. The review explores four main subtypes of M-HLH: (1) HLH as the initial presentation of malignancy, (2) Chemotherapy Associated HLH, (3) Cytokine Release Syndrome (CRS) Associated HLH-like Syndrome, and (4) immune effector cell-associated HLH-like syndrome. Diagnosis is complicated by overlap with cancer symptoms and limitations of existing criteria. The Optimized HLH Inflammatory (OHI) index shows promise in early identification of hyperinflammation in new-onset hematologic malignancies. Treatment approaches must balance controlling hyperinflammation with addressing the underlying malignancy. Emerging therapies, including targeted agents like anakinra, ruxolitinib, and emapalumab, offer new management possibilities. This review examines the current understanding of M-HLH pathophysiology, diagnostic approaches, and treatment strategies for each subtype. It underscores the critical need for further research to unravel underlying mechanisms and establish evidence-based treatment protocols. Given the complexity of M-HLH, international collaborative efforts are essential to advance knowledge and improve patient outcomes.

Therapy adherence can significantly influence the outcome of cancer patients. The prospective, non-interventional CARO study (NCT02970747) investigated adherence, effectiveness, and safety of carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) in the German real-world setting. In total, 359 patients were included at 69 sites. Data on carfilzomib combination regimens were evaluated for three treatment cohorts: carfilzomib with lenalidomide and dexamethasone (KRd), with dexamethasone only (Kd) or with daratumumab and dexamethasone (KdD). Encouragingly, patients maintained levels of treatment adherence ≥95% to carfilzomib across cohorts. The effectiveness outcomes of CARO were in line with previous data. Median PFS (95% CI) was 17.5 months (14.5, 24.7 [KRd]), 13.4 months (7.0, 18.1 [Kd]), and 15.6 months (9.9, NA [KdD]), respectively. Median OS was 38.9 months (31.5, 53.9 [KRd]), 24.2 months (17.3, 36.8 [Kd]), and not reached (KdD). Overall, the CARO study impressively demonstrates efficacy and safety of KRd, Kd, and KdD regimen in real-world.

Access to allogeneic and autologous hematopoietic stem cell transplantation (SCT) remains inadequate despite its curative potential across hematologic malignancies. In 2015, Hartford HealthCare (HHC) and the Memorial Sloan Kettering Cancer Center (MSK) established the Shared Care Model (SCM) with a primary aim of enhancing SCT access for HHC patients. The SCM comprises several components: an SCT-dedicated nurse-navigator, a health-information exchange for record sharing, telemedicine, and ongoing training of HHC clinicians in transplant patient selection and management. We evaluated the SCM's impact on SCT access across 126 patients with acute leukemia, myelodysplastic syndrome, and multiple myeloma from 2016-2020. The SCM facilitated 34 referrals. Socio-economic status of HHC referrals by Area Deprivation Index was significantly inferior (38 vs. 14, p < 0.001) when compared to 3,108 non-SCM referrals to MSK during the same period. Allogeneic recipients spent 68-247 days away from home, and autologous recipients 15-48, both requiring few subsequent visits to MSK.

Advances in treating classic Hodgkin lymphoma (cHL) have improved cure rates, with overall survival exceeding 80%, resulting in a growing population of survivors at risk of long-term complications, particularly cardiac and pulmonary toxicity. Bleomycin, a key component of combination chemotherapy, is associated with bleomycin-induced pulmonary toxicity (BPT). Using label-free quantification nano liquid chromatography-tandem mass spectrometry, protein expression in diagnostic lymphoma samples from patients with and without BPT was compared. Results showed differential protein expression and disrupted cellular pathways, suggesting biological differences in BPT risk. Immunohistochemical analysis revealed higher expression of JAK3, BID, and MMP9, and lower expression of CD20, TPD52, and PIK3R4 in patients with BPT. High BID and low CD20 expression were associated with inferior overall survival, while high BID and low JAK3 and CD20 expression were linked to poorer progression-free survival. These findings highlight altered protein profiles in pretreatment cHL biopsies associated with BPT development.

We retrospectively investigated the impact of CTLA-4 polymorphism on outcomes for adult patients who received single-unit cord blood transplantation (CBT) at our institution. CTLA-4 genotyping was performed using real-time polymerase chain reaction with the TaqMan^® SNP genotyping assay for rs231775. This study included 143 recipient-donor pairs. The multivariate analysis showed that recipient rs231775 AA was associated with worse overall survival (OS) (hazard ratio [HR], 2.92; p = 0.008) and a higher relapse rate (HR, 4.79; p = 0.002), but donor rs231775 was not. The rs231775 polymorphism in recipients and donors did not affect non-relapse mortality, hematopoietic recovery, or acute and chronic graft-versus-host disease. The beneficial effects of rs231775 GG+GA recipients on OS and relapse were notable in subgroups of patients with high-risk disease status and those with myeloid diseases. The polymorphism of CTLA-4 rs231775in recipients might be associated with the clinical outcomes of single-unit CBT.