Hematology/ Oncology and Stem Cell Therapy最新文献

Background and objectives: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukemia (CN-AML) renders it an ongoing therapeutic challenge. The European LeukemiaNet (ELN) 2017 guidelines attempted to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains unclear due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological and molecular features as well as treatment outcomes and, consequently, to investigate the local applicability of a triple-mutation testing approach for risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin 1 (NPM1), fms-related receptor tyrosine kinase 3 internal tandem duplication (FLT3-ITD), and CCAAT enhancer-binding protein alpha (CEBPA) mutation status.

Materials and methods: A review of cytogenetic results for adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via a review of clinical and laboratory data and additional molecular testing on stored DNA samples to allow for mutation-based risk stratification and outcome analysis.

Results: In total, 218 patients with AML were identified, of which 33% were cytogenetically normal. NPM1, FLT3-ITD, and CEBPA mutations were found in 39%, 34%, and 9% of CN-AML cases, respectively. Retrospective risk stratification according to mutations in these three genes accurately identified both patients at a high risk of induction-resistant disease and those who required an allogeneic stem cell transplant in their first complete remission.

Conclusion: Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to those of European cohorts. Limited mutation analysis in the form of triple-mutation testing proved to be an economical and therapeutically informative prognostication approach for CN-AML in a resource-limited setting.

Tenosynovial giant cell tumor (TGCT) is a rare inflammatory disorder affecting the joint synovium, bursae, and tendon sheaths that causes non-specific and often insidious joint discomfort. The application of systemic chemotherapy has been limited due to poor and unsustained disease responses. Surgery with or without adjuvant radiation is the primary treatment modality for TGCT. With its locally destructive nature and increased recurrence, multiple surgical interventions become necessary throughout the course of the disease, leading to disfigurement, decreased quality of life, and increased mortality. However, owing to recent evidence demonstrating the overexpression of colony-stimulating factor 1 (CSF-1) in TGCT, selective tyrosine kinase inhibitors targeting CSF-1 receptors are being developed. Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

Carfilzomib is an irreversible proteasome inhibitor currently approved for the treatment of relapsed multiple myeloma. It has been implicated as a cause of thrombotic microangiopathy (TMA) in several case reports. The incidence, risk factors, and treatment of carfilzomib-related TMA remain unclear. Here we describe the clinical presentation and outcome of a 58-year-old man with biopsy-proven TMA that occurred following treatment with carfilzomib-based therapy. We also reviewed the published literature with regard to the incidence, risk factors, treatment options, and outcome of carfilzomib-related TMA.

Background: Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with a vendor-mediated supply chain capable of delivering high-acuity care in the comfort of the patients' own homes. In our program, we used the existing ACH platform to deliver post-HCT care for recipients of auto-HCT.

Patients and methods: Four patients (female = 2, 50%) with MM, with a median age of 60 (range, 40-74) years, were admitted to the inpatient Blood and Marrow Transplant (BMT) unit. The conditioning regimen consisted of melphalan 200 mg/m², administered on day -2. All patients received stem cell infusion (day 0) in the inpatient setting, with a median dose of 3.64 (range, 2.92-8.22) × 10⁶/kg CD34 cells.

Results: Patients were discharged to their homes after completing the infusion on day 0 or day +1 at the latest. Post-infusion care was provided by the ACH team in coordination with the BMT team. The median time intervals to absolute neutrophil count and platelet engraftment were 12 (range, 11-13) and 11 (range, 9-16) days, respectively. All patients were successfully discharged from the ACH program at a median of day +14 (range, day +14 to day +15).

Conclusions: Our results highlight the feasibility of delivering post-HCT care for auto-HCT recipients in the home setting and confirm the generalizability of this approach.

The availability of novel targeted agents has revolutionized the management of chronic lymphocytic leukemia (CLL). Both B-cell lymphoma 2 (BCL2) and Bruton tyrosine kinase (BTK) inhibitors are highly effective agents for CLL treatment. Several clinical trials have demonstrated the efficacy and safety of these agents in the management of newly diagnosed and relapsed/refractory CLL. This has led to two broad approaches in the frontline management of CLL, namely venetoclax-based time-limited therapy versus BTK inhibitor-based continuous therapy. In this review, we discussed why we consider venetoclax-based therapy as a suitable frontline option for patients with CLL.

Background and objectives: Almost 25% of patients with lymphoma may have relapse or develop refractory disease, and a majority of such patients undergo salvage chemotherapy and autologous stem cell transplantation (ASCT). Data on venous thromboembolism (VTE) in this setting are scarce. This study aimed to investigate the prevalence and factors that may increase the risk of VTE in such patients.

Patients and methods: Adult patients who were diagnosed with lymphoma and received salvage chemotherapy and ASCT were included in the study, and the subgroup with radiologically confirmed VTE were identified. Correlations between different clinical and laboratory variables and VTE were evaluated.

Results: A total of 216 patients (median age, 31 [range, 19-60] years) were enrolled in the study. Most patients (n = 140, 64.8%) had Hodgkin's lymphoma, while 54 (25.0%) had diffuse large B-cell lymphoma. A total of 36 (16.7%) patients had VTE, mostly as upper extremity deep vein thrombosis (n = 28, 77.8%); 18 (50%) of the cases were related to central venous catheter insertion. Thrombosis rates were higher among patients with high lactate dehydrogenase (LDH) level (29.2% vs. 5.9%, p < 0.001), those with mediastinal involvement (25.9% vs. 11.5%, p = 0.025). and those with longer hospital stay (22.3% vs.9.5%, p = 0.036). In the multivariate analysis, high LDH level (odds ratio (OR), 6.53; p < 0.001), mediastinal involvement (OR, 2.70; p = 0.005) and hospital stay ≥24 days (OR, 2.71; p = 0.007) were all associated with significantly higher VTE rates.

Conclusion: Patients with relapsed lymphoma undergoing salvage chemotherapy and ASCT are at higher risk for VTE, especially in those with high LDH level, mediastinal involvement, and prolonged hospital stay. If no contraindications exist, thromboprophylaxis might be considered in these settings.

BTK (Bruton's tyrosine kinase) inhibitors are highly effective front-line therapy for CLL (chronic lymphocytic leukemia) due to high response rates and prolonged progression-free survival, even in patients with high-risk disease features. They are also generally well tolerated, with the newer BTK inhibitors demonstrating better tolerability than ibrutinib while maintaining efficacy. Adverse effects such as bleeding or infections are usually manageable with supportive care or dose adjustments. Orally administered BTK inhibitors do not require intensive or inpatient monitoring and improve quality-of-life outcomes. Moreover, the established activity of venetoclax in the setting of BTK inhibitor failure is also reassuring as a salvage option. Nevertheless, the advantage of venetoclax as a time-limited treatment option is substantial, despite its inferior progression-free survival, since these patients can get another challenge with a reasonable chance of success. BTK inhibitors after venetoclax may be effective, but long-term data is limited. Given these reasons, BTK inhibitors remain the preferred treatment option as initial therapy for patients with CLL, especially those with del17p or TP53 mutations.

Background and objectives: Three different scores were addressed as predictors of outcomes in autologous stem cell transplant (Auto SCT): one was calculated by pretransplant characteristics (European Society for Blood and Marrow Transplantation [EBMT] risk score), and two were calculated at the onset of febrile neutropenia (Multinational Association for Supportive Care in Cancer [MASCC] and Quick Sequential Organ Failure Assessment [qSOFA]). We considered bloodstream infection (BSI), carbapenem prescription, admission to the intensive care unit (ICU), and mortality as outcomes.

Patients: A total of 309 patients with a median age of 54 years were enrolled.

Results: Patients with EBMT score ≥4 (EBMT 4+) had higher ICU rates (14% vs. 4%; p < 0.01) and more carbapenem prescriptions (61% vs. 38%; p < 0.001) than those with EBMT score <4. MASCC <21 points (MASCC HR) was associated with carbapenem prescription (59% vs. 44%; p = 0.013), ICU (19% vs. 3%; p < 0.01), and death (4% vs. 0; p = 0.014). Patients with at least two points by qSOFA (qSOFA 2+) had more frequent BSI (55% vs. 22%; p = 0.03), ICU admissions (73% vs. 7; p < 0.01), and death (18% vs. 0.7, p = 0.02). EBMT 4+ and MASCC HR achieved the best sensitivities for ICU. For death, the best sensitivity was obtained with MASCC.

Conclusion: In conclusion, risk scores for Auto SCT showed an association with outcomes and had different performances when combined or used alone. Therefore, risk scores for Auto SCT are useful in supportive care and clinical surveillance in stem cell transplant recipients.

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study, clinical outcomes and health resource utilization (HRU) were compared in 32 patients with VOD who had a PD (PD+) post-HCT versus 27 patients who did not (PD-). Nine patients also had a CT (7 PD+ and 2 PD-). PD + patients were more likely than PD-patients to have received myeloablative conditioning (100% vs. 85.2%; p = 0.04) and have severe or very severe VOD (100% vs. 56% p < 0.01). Mechanical obstruction (38%) and hypotension (38%) were common complications, and 13% developed peritonitis. While the frequencies of cardiac dysfunction and acute kidney injury were comparable between both groups, respiratory support and its median duration were higher in PD + patients. The hospital and intensive care unit length of stay, albumin use, and the duration of defibrotide and albumin therapy was significantly longer in PD + patients. At a median follow-up of 1.04 years (range:0.03-14.6), the 2-year overall survival was similar in both groups (53.8% vs. 51.5%; p = 0.73). Although PD use was similar between 1995 and 2007 vs. 2008-2021; (47% vs. 58%; p = 0.65), day+100 mortality was improved in recent years (53.3% vs. 17.8%; p = 0.01), coinciding with the use of defibrotide (0% vs. 84%; p < 0.01). PD in pediatric patients with VOD post-HCT, although associated with increased HRU, was safe when clinically indicated and did not adversely impact clinical outcomes.