Hematology/ Oncology and Stem Cell Therapy最新文献

Sickle Cell Disease (SCD) is a hereditary blood disorder affecting beta hemoglobin. This disorder causes sickle-shaped red blood cells with decreased oxygen-carrying capacity resulting in vaso-occlusive crises. These crises are often treated with analgesics, antibiotics, IV fluids, supplementary oxygen, and allogeneic blood transfusion. This treatment regimen becomes complicated when caring for SCD patients for whom blood transfusion is not an option. Blood transfusion may not be an option due to the patient's religious, personal, or medical concerns and in scenarios where blood is not available for transfusion. Some examples include the patient being a Jehovah's Witness, blood-borne pathogens concerns, or prior history of multiple alloantibodies and severe transfusion reactions. The number of patients in these categories is growing. The patients and their autonomy should be respected during treatment. This review focuses on the currently available modalities to best manage this subgroup of SCD patients without blood transfusion, including new professional guidelines and new therapies to reduce the severity of SCD as approved by the Food and Drug Administration since 2017.

Background and objectives: Area of residence may adversely affect survival and outcomes in many cancers. The objective of this study was to evaluate the impact of geographical and demographic disparities on survival of patients with colorectal cancer.

Materials and methods: Data were obtained from the National Cancer Database (NCDB) colon, rectosigmoid, and rectal datasets. Patients were categorized by area of residence, namely, metropolitan (MA), urban (UA), or rural (RA). Sociodemographic and tumor-related data were collected and analyzed to evaluate variables affecting overall survival (OS).

Results: In total, 973,139 patients between 2004 and 2013 were included in the study, of which 83%, 15%, and 2% were MA, UA, and RA residents, respectively. RA and UA patients were mostly white male with low income and no comorbidities. In univariate analysis, OS was worse for RA (hazard ratio [HR] 1.10) and UA (HR 1.06) colorectal cancer patients than that for MA colorectal cancer patients. In multivariate analysis revealed significant association between OS and geographic residence, with worse OS for RA (HR 1.02, p = 0.04) and UA (HR 1.01, p = 0.003) patients. Black (HR 1.14) and Native American (HR 1.17) patients had worse outcomes, while Asians (HR 0.8), women (HR 0.88), and patients with higher income had improved OS (HR 0.88).

Conclusion: The differences in the OS for RA and UA patients with colorectal cancer were significantly driven by economic disparity. Area of residence represents an important factor independently limiting access to care, particularly in geographically isolated individuals.

Background: Mutations in JAK2/STAT5 proliferation pathway genes are key in the diagnosis of myeloproliferative neoplasms (MPN^BCR/ABLneg), with JAK2V617F being found in 50-97% of MPN^BCR/ABLneg subtypes. Low JAK2V617F positivity at our facility suggested that our South African MPN^BCR/ABLneg population may have a different mutational landscape.

Objectives: We aimed to determine the JAK2/STAT5 mutation frequencies associated with our local MPN^BCR/ABLneg population, thus determining the relevance of these molecular tests in this group. We also investigated the haematopathological relevance of each test request, to assess testing practises.

Method: This study involved the retrospective audit of 886 patients for whom JAK2V617F mutation testing had been requested for a suspected MPN diagnosis. FBC indices, erythropoietin levels and bone marrow biopsy results were used to classify the patients. JAK2V617F ^negative patient DNA was tested for calreticulin (CALR) exon9, myeloproliferative leukaemia protein (MPL) codon515 and JAK2 exon12 mutations.

Results: Only 23% of the patients demonstrated JAK2V617F positivity, with an additional 29 cases of CALR/MPL mutations being detected. Mutations were only detected in patients with abnormal FBC indices, as expected, yet 37% of the test requests were not associated with abnormal parameters at the time of testing. Mutation frequencies were as follows: Polycythaemia Vera: 97% JAK2V617F/3% (JAK2, CALR, MPL) triple negative; Essential thrombocythemia: 72% JAK2V617F/23%CALR/5%triple negative; Primary Myelofibrosis: 78%JAK2V617F/16%CALR/6%triple negative.

Conclusion: Our study demonstrated that our MPN^BCR/ABLneg patients have a similar genetic landscape to other MPN populations, with >93% being able to be diagnosed by testing for the JAK2V617F and CALR exon9 mutations alone. Adoption of the WHO 2016 guidelines is recommended to guide testing practices.

Objective/background: Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal.

Methods: We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy.

Results: Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALC_Leuk) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6-14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3-5.1).

Conclusion: The grade of CRS and ALC_Leuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.

Background: Hepatic veno-occlusive disease (VOD), also termed as sinusoidal obstruction syndrome (SOS), is a lethal complication after hematopoietic stem cell transplantation (HSCT). Various factors put patients undergoing allogeneic HSCT at an increased risk for VOD. Thrombomodulin (TM) is an important factor which has a wide range of effects, including anticoagulant, anti-inflammatory, angiogenic, and protective effect, on endothelial cells. It plays a role in preventing excessive coagulation and thrombosis by binding with thrombin and inhibiting the coagulation cascade. There are a limited number of options for the prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, as prophylactic therapy might be able to prevent veno-occlusive complications after stem cell transplantation.

Methods: A literature search was performed on PubMed, Embase, and Web of Science. We used the following Mesh terms and Emtree terms, "Hepatic Veno-Occlusive Diseases" OR "Sinusoidal Obstruction" OR "Stem Cell Transplantations " AND "Thrombomodulin" from the inception of data up to April 1, 2021. The PICO (Patient/Population, Intervention, Comparison and Outcomes) framework was used for the literature search.

Results: For the VOD incidence after HSCTstem cell transplantation, the result was in favor of rTM with a risk ratio (RR) of 0.53 (I² = 0%, 95% confidence interval [CI] = 0.32-0.89). The incidence of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT was reduced in rTM group. The RR for incidence of TA-TMA was 0.48 (I² = 62%, 95% CI = 0.20-1.17) favoring rTM. The RR for incidence of graft-versus-host disease (GvHD) was also lower in rTM group, 0.48 (I² = 64%, 95% CI = 0.32-0.72).

Conclusion: In our meta-analysis, we evaluate the efficacy and safety of rTM in the prevention of SOS after HSCT. According to our results, rTM use led to a significant reduction in SOS episodes, TA-TMA, and GvHD after HSCT.

Mantle cell lymphoma is a rare subtype of non-Hodgkin's lymphoma with poor prognosis and continue to be challenging to treat. The choice of first line induction regimen remains a topic of debate due paucity of clinical trials. We retrospectively evaluated 66 patients diagnosed with mantle cell lymphoma who achieved first complete response after induction chemotherapy followed by autologous stem cell transplant. Treatment groups were divided into low-intensity versus high-intensity regimens. Our data showed the intensity of induction regimen does not impact posttransplant outcomes of mantle cell lymphoma who underwent autologous stem cell transplant in first complete response.

The Internet of Things (IoT) has penetrated many aspects of everyday human life. The use of IoT in healthcare has been expanding over the past few years. In this review, we highlighted the current applications of IoT in the medical literature, along with the challenges and opportunities. IoT use mainly involves sensors and wearables, with potential applications in improving the quality of life, personal health monitoring, and diagnosis of diseases. Our literature review highlights that the current main application studied in the literature is physical activity tracking. In addition, we discuss the current technologies that would help IoT-enabled devices achieve safe, quick, and meaningful data transfer. These technologies include machine learning/artificial intelligence, 5G, and blockchain. Data on current IoT-enabled devices are still limited, and future research should address these devices' effect on patients' outcomes and the methods by which their integration in healthcare will avoid increasing costs.

Background: Immune checkpoint inhibitors (ICIs) are the newest class of anticancer drugs. Pneumonitis is increasingly being recognized as a potential complication of these agents.

Methods: We conducted a retrospective study of patients who received ICIs at a comprehensive cancer center. We collected data on demographics, type of malignancy, type of ICI agent, incidence of pneumonitis up to 6 weeks after receiving ICI agent, clinical characteristics, and risk factors for overall survival in patients who develop pneumonitis.

Results: A total of 654 patients received ICIs during the study period. The most common type of cancer for which ICI was given was adenocarcinoma of the lung (29%), followed by renal cell cancer (12%) and squamous cell lung cancer (12%). Among the study patients, 41% received nivolumab and 32% received pembrolizumab. Other patients in the study received combination of ICIs or ICI plus chemotherapeutic agent, or were part of clinical trial involving ICI. Overall 42 (6.4%) patients developed pneumonitis within 6 weeks after the last dose of treatment of any ICI agent. Of these, 81% of patients had Grade ≥ 2 pneumonitis and 45% of these required hospital admission for pneumonitis, with 10% of them requiring admission to intensive care unit. Overall, patients who received pembrolizumab-containing regimen, had prior chemotherapy, or who never had cancer-related surgery had increased risk of death.

Conclusion: Our large retrospective study shows real-life data of incidence of pneumonitis in patients who are treated with ICIs for cancer treatment. Our data indicate that the incidence of pneumonitis is overall lower than that reported previously with relatively good outcomes.

Objectives: The aim of this systematic review is to investigate different diagnostic methods and the available treatment options for subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

Methods: We searched PubMed, Web of Science, SCOPUS, EBSCO, and CINAHL Plus for published case reports of SPTCL. From each record, we extracted data of the diagnostic methods, immunohistochemical profile, clinical characteristics, and the treatment approaches provided. Data were summarized and narratively synthesized to highlight the various diagnostic methods and treatment options of SPTCL.

Results: Our literature search yielded 1293 unique citations. Following screening, nine articles reporting a total of 15 cases were included in this systematic review. All patients presented with subcutaneous nodules. Three of the 15 cases were initially misdiagnosed. The atypical lymphoid cells were positive for CD2, CD3, granzyme B, and TIA-1 and negative for CD1a, EBER, and CD20 in all the reported cases. The atypical lymphoid cells were positive for CD45RO in four out of seven cases, positive for CD56 in three out of 12 cases tested, while positive for CD5 and CD8 in the majority of cases. Therapy ranged from topical agents to immunosuppressive agents all the way to multiagent chemotherapy.

Conclusion: SPTCL is a rare lymphoma. Diagnosis is highly dependent on the immunohistochemical stains added to histopathologic and radiologic findings. Therapy is dependent on the pace of the disease, with encouraging results obtained with single-agent cyclosporine.