Risk assessment of patients with hematologic malignancies who develop fever accompanied by pulmonary infiltrates: a historical cohort study

BACKGROUND: The mortality rate associated with fever accompanied by pulmonary infiltrates after chemotherapy for hematologic malignancies remains higher than the corresponding rate associated with febrile neutropenia without pulmonary infiltrates. Nonetheless, few studies have focused on the factors that predict outcome for patients with lung infiltrates. The purpose of the current study was to construct a risk model for clinical use by assessing the factors that affect outcome for patients with fever and pulmonary infiltrates. METHODS: A historical cohort of 110 patients with hematologic malignancies who developed fever and pulmonary infiltrates was examined. Using parameters for which data were available at the onset of lung infiltrates, univariate and multivariate analyses were performed to assess factors affecting outcome. After a value of one point was assigned to each significant variable, a prediction score was calculated for each patient; scores were used to generate a system for identifying patients with a low risk of death due to fever accompanied by pulmonary infiltrates. RESULTS: The crude mortality rate associated with pulmonary infiltrates was 23%; factors associated with cure included a favorable change in white blood cell counts (odds ratio [OR], 5.6; 95% confidence interval [CI], 1.7-18.9; P = 0.001), C-reactive protein levels < 10 mg/dL (OR, 4.6; 95% CI, 1.6-13.8; P = 0.001), and serum albumin levels > or = 3 g/dL (OR, 3.2; 95% CI, 1.4-7.3; P = 0.004). Low-risk patients (risk score, 2-3) and high-risk patients (risk score, 0-1) had survival rates of 95% and 46%, respectively (P < 0.0001). The risk model had a specificity of 88% and a positive predictive value of 95%. CONCLUSIONS: The risk model tested in the current study accurately predicted the survival of patients with hematologic malignancies who developed fever with pulmonary infiltrates. Once prospectively validated, the model could be used to select patients for trials involving novel diagnostic and therapeutic strategies.     

Risk factor for invasive zygomycosis in patients with hematologic malignancies

Zygomycosis (mucormycosis) is a relatively uncommon infection in immunocompromised patients most often diagnosed in patients with haematological malignancies and neutropenia. Postmortem series demonstrate a high mortality rate up to 80%. Pulmonary involvement mimicking the more frequently diagnosed invasive aspergillosis is the typical clinical presentation. Other risk factors for the development of zygomycosis that have been described in other patient populations include diabetic ketoacidosis, iron overload, use of deferoxamine and steroids. If these factors are also associated with zygomycosis in patients with haematological malignancies has not been described. In a retrospective case-control study including 13 patients with zygomycosis and 13 control patients with the same underlying diseases, without zygomycosis we determined the frequency of various risk factors. Patients with zygomycosis experienced a longer period of neutropenia (17 vs. 13 days) and lymphopenia (23 vs. 20 days). A relapse of their underlying disease was diagnosed more frequently in patients with zygomycosis (7/13 vs. 3/13) as were a diagnosis of diabetes mellitus (6/13 vs. 3/13) and a cardiovascular disease (6/13 vs. 1/13). The previous use of steroids was more frequent in patients with zygomycosis (8/13 vs. 4/13) as was a systemic antifungal prophylaxis with itraconazole (9/13 vs. 4/13). Knowledge of these risk factors may be of benefit in diagnosing and monitoring zygomycosis in patients with haematological malignancies.     

老年综合评估在老年血液系统肿瘤患者中的研究进展

随着老年人血液系统肿瘤发病率的逐年升高,如何更好地评估老年血液肿瘤患者对化疗的耐受性是困扰临床医师的问题.最近老年综合评估开始用于老年血液肿瘤患者,研究发现老年综合评估可以判断患者预后,预测患者对治疗的耐受性,并有可能指导治疗决策.文章对国内外老年综合评估在血液肿瘤的研究现状进行综述.     

Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies.

Risk factors for invasive aspergillosis (IA) are incompletely identified and may undergo changes due to differences in medical practice. A cohort of 189 consecutive, adult patients with neutropenia hospitalized in the hemato-oncology ward of the University hospital Berne between 1995 and 1999 were included in a retrospective study to assess risk factors for IA. In total, 45 IA cases (nine proven, three probable, 33 possible), 11 patients with refractory fever and 133 controls were analyzed. IA cases had more often acute leukemia or myelodysplastic syndrome (MDS) (88 vs 38%, P < 0.001) and a longer duration of neutropenia (mean 20.6 vs 9.9 days, P < 0.001). They also had fewer neutropenic episodes during the preceding 6 months (mean 0.42 vs 1.03, P < 0.001), that is, confirmed (82%) and probable (73%) IA occurred most often during the induction cycle. A short time interval ( < or = 14 days) between neutropenic episodes increased the risk of IA four-fold (P = 0.06). Bacteremia, however, was not related to the number of preceding neutropenic episodes. Therefore, neutropenic patients with leukemia or MDS have the highest risk of IA. The risk is highest during the first induction cycle of treatment and increases with short-time intervals between treatment cycles.     

Pulmonary disease in patients with hematologic malignancies

Patients with hematologic neoplasms frequently experience pulmonary disease. The possibility of a malignant involvement of the lung parenchyma is a well recognized and not unusual event, secondary spread due to lymphoproliferative disorders being the most common situation. Furthermore, the development and the advances in treatment options such as hematopoietic stem cell transplantation, radiation therapy and/or combined drug regimen use have significantly widened the spectrum of non-neoplastic pulmonary complications that can crop up in these patients. Infections, drug/radiation-induced toxicity, and graft-versus-host disease (GVHD)-related complications account by now for most pulmonary problems in hematologic patients and represent a difficult challenge both in diagnostic and in therapeutic terms for the clinician. The aim of this review is to highlight the clinicopathologic spectrum of lung diseases which can occur in the setting of hematologic malignancies. A particular emphasis is devoted to the diagnostic approach, high-resolution computed tomography (HRCT) assuming a key role since different patterns of CT abnormalities are associated with a different yield of the available diagnostic tools and may help in narrowing the differential diagnosis.     

Fusarium infections in patients with hematologic malignancies

Two cases of Fusarium infection in patients with refractory hematologic malignancies are reported. In one patient septicemia progressed to death in septic shock. Miconazole showed some effect in clearing the lesions. There is some evidence that mycotoxins are related with Fusarium infections since severe myositis occurred in our patient. The other patient had a T-cell lymphoma, undergoing allogeneic bone marrow transplantation. The course was also complicated by Fusarium infection of the skin. This patient died of multiorgan failure. Recent literature on Fusarium is reviewed.     

替加环素治疗化疗后粒细胞缺乏伴发热恶性血液病患者的疗效观察

目的:探讨替加环素治疗 粒细胞缺乏伴发热血液病患者的疗效及安全性。方法:选择我院血液科从2014年9月至2018年11月收治的79例恶性血液病经化疗后粒细胞缺乏伴发热的住院感染患者,采用随机平行对照法,对照组设定为更换替加环素（39例）抗感染治疗,观察组设定为初始即联合其它抗菌药物（40例）抗感染治疗,回顾性分析不同组别患者抗感染治疗的临床疗效和药物相关不良反应。结果:79例患者中,17例（21.52%）痊愈,43例（54.43%）感染得到控制,16例（20.25%）无效,3例（3.80%）死亡。观察组和对照组抗菌治疗总有效率分别为77.5%和74.36%,两组总有效率差异无统计学意义（P＞0.05）。替加环素主要不良反应为恶心呕吐等消化道症状,耐受性良好。结论:替加环素抗菌活性强、抗菌谱广,具有良好的疗效和安全性,可作为恶性血液病化疗后粒细胞缺乏伴发热患者替补方案或经验治疗的选择。     

Direct oral anticoagulants in patients with hematologic malignancies

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation—therapy was maintained until the platelet count was ≥50 × 10⁹/L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.     

TNF-alpha targeted therapeutic approaches in patients with hematologic malignancies

Tumor necrosis factor (TNF)-alpha is a major effector and regulatory cytokine with a pleiotropic role in the pathogenesis of several immune-regulated diseases, including graft versus host disease (GVHD) and hematologic malignancies, such as multiple myeloma (MM), myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Curative treatment for the above diseases are not currently available for most patients. Therapeutic approaches inactivating or blocking TNF-alpha are being evaluated in clinical trials. This review describes the development of the soluble TNF-alpha receptor (p75 TNF-R: Fc; etanercept) and other agents inactivating or blocking TNF-alpha in the management of patients with hematologic malignancies. The satisfactory safety profile of etanercept--as demonstrated in patients with autoimmune diseases--has been confirmed in patients with hematologic malignancies and GVHD. Studies to assess whether etanercept, either as a single agent or in combination with cytotoxic and/or immune therapy, may increase response rates and/or survival in patients with MM, MDS, AML and other hematologic malignancies are now warranted.     

Fusarium infections in patients with hematologic malignancies

Two cases of Fusarium infection in patients with refractory hematologic malignancies are reported. In one patient septicemia progressed to death in septic shock. Miconazole showed some effect in clearing the lesions. There is some evidence that mycotoxins are related with Fusarium infections since severe myositis occurred in our patient. The other patient had a T-cell lymphoma, undergoing allogeneic bone marrow transplantation. The course was also complicated by Fusarium infection of the skin. This patient died of multiorgan failure. Recent literature on Fusarium is reviewed.     

The safety of dental extractions in patients with hematologic malignancies

Dental disorders have been recognized as major sources of infection in patients with hematologic malignancies (HM). Management of severe dental infections usually includes dental extractions (DE), but the safety of extractions in patients with HM who are at risk for bleeding, sepsis, and poor wound healing has not been well established. In conjunction with an aggressive program of dental care, 142 DE were performed in 26 patients with acute leukemia, myelodysplastic syndromes, and myeloproliferative disorders. Granulocytopenia (less than 1,000 granulocytes/microL) was present during or within ten days following surgery in 14 patients. In these 14 patients (101 DE), the mean granulocyte count was less than 450/microL, with a median duration of granulocytopenia following surgery of 32 days (range, four to 169 days). Thrombocytopenia (less than 100,000 platelets/microL) occurred during or within two days following surgery in 13 patients (80 DE), with a mean platelet count of 63,500/microL. Transfusions were given for platelet counts less than 50,000/microL. All DE were performed without significant complications. Bleeding was minor to moderate and easily controlled with local measures; no patient required transfusion due to hemorrhage. Average maximum temperature 24 hours after DE was 37.7 degrees C. No episodes of bacteremia were documented within ten days of DE. Minor delay in wound healing was observed in two patients. We conclude that DE can be safely performed in patients with HM in combination with aggressive supportive care.     

Risk factors for the assessment of patients with pulmonary embolism

Pulmonary embolism (PE) occurs frequently among cancer patients, with a spectrum ranging from small, clinically insignificant thrombi to life-threatening massive PE. It is fatal in as many as 14% of cancer patients, primarily by producing right ventricular heart failure and cardiogenic shock. PE diagnosis is difficult because the signs and symptoms imitate other commonly occurring diseases. Clinicians must be able to integrate a wide array of diagnostic imaging tools and laboratory tests to ensure rapid assessment and diagnosis. Risk stratification with the use of cardiac biomarkers and imaging tests to evaluate right ventricular function will identify treatment options. Hemodynamically stable patients can be treated effectively with anticoagulation alone, whereas those with right ventricular dysfunction require an aggressive strategy with thrombolysis, surgical embolectomy, or a catheter-based intervention. When anticoagulation is contraindicated, a vena caval filter may be deployed. PE treatment must be customized to the individual and consider the existing thrombus burden, presence of underlying cardiopulmonary disease and right side heart dysfunction, and cancer status of the patient. Clinicians should focus on providing adequate thromboprophylaxis in hospitalized cancer patients to avoid PE treatment.     

Diagnosis and treatment of fungal infections in patients with hematologic malignancies

A diagnosis of deep-seated mycosis was made in 54 patients with hematologic malignancies, severe neutropenia and fever, based on a set of clinical and laboratory criteria. Standardized antifungal treatment was started in 31 patients who seven days after onset of fever had not responded to antibiotics; the fungal infection was cured in 13, all of whom had a simultaneous remission of neutropenia, whereas the other 18 who did not respond to antifungal treatment, all had a falling or static neutrophil count. None of the 23 patients who were given no or inadequate antifungal treatment survived regardless of the neutrophil count and/or phase of the hematologic disease. We discuss the suitability of utilizing empirical criteria for a diagnosis of disseminated fungal infection as a basis for starting antifungal therapy in this type of patient.     

Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19⁺ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.Subject terms: Translational research, Haematological cancer, Adaptive immunity     

Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection

BACKGROUND: Invasive infection by Fusarium sp. is associated with high mortality in patients with hematologic cancer. Yet to the authors' knowledge, little is known regarding predictors of adverse outcome. METHODS: The authors conducted a retrospective review of the records of patients with hematologic carcinoma and invasive fusariosis who were treated at one institution in the U.S. and at 11 centers in Brazil. RESULTS: The records of 84 patients were evaluated. Neutropenia was present in 83% and 33 patients had undergone stem cell transplantation. Only 18 patients (21%) were alive 90 days after the diagnosis of fusariosis. Multivariate predictors of poor outcome were persistent neutropenia (hazard ratio [HR] of 5.43; 95% confidence interval [95% CI], 2.64-11.11) and use of corticosteroids (HR of 2.18; 95% CI, 1.98-3.96). The actuarial survival rate of patients without any of these factors was 67% compared with 30% for patients who recovered from neutropenia but were receiving corticosteroids and 4% for patients with persistent neutropenia only. None of the patients with both risk factors survived (P<0.0001). CONCLUSIONS: Measures to reduce the duration of neutropenia, as well as the judicious use of corticosteroids, may reduce the high mortality rate of fusariosis in patients with hematologic cancer.     

造血干细胞移植治疗恶性血液病的临床观察

目的:观察我院骨髓移植治疗恶性血液病的疗效、探讨移植相关并发症的预防及处理等问题。方法:4例行HLA相合的同胞间异基因外周干细胞移植(Allo-PBSCT)、2例行自体外周干细胞移植(APBSCT)和1例行自体骨髓移植(Au-to-BMT)。结果:全部病例均成功造血重建。中性粒细胞≥0·5×109/L平均时间为11天;血小板≥20×109/L平均时间为16天;发生Ⅱ~Ⅲ度aGVHD1例,cGVHD1例,溶血性贫血2例,间质性肺炎2例,中位随访时间18(6~42)月,全部病例现均存活。结论:骨髓移植治疗恶性血液病有较好疗效。