The important role of intensive induction chemotherapy in the treatment of acute myeloid leukemia.

Introduction: Intensive induction chemotherapy followed by post-remission consolidation and/or allogeneic hematopoietic transplantation has been a standard-of-care therapy for acute myeloid leukemia (AML) for decades. In recent years, a plethora of new agents have been approved for AML treatment, dramatically changing the AML treatment landscape.Areas covered: This review provides an overview of the current role of intensive chemotherapy in the changing AML treatment landscape. PubMed-indexed publications (through 2020) and abstracts presented at major national and international conferences were reviewed for inclusion.Expert opinion: While intensive chemotherapy is standard-of-care therapy for younger patients with AML, older patients were historically viewed as universally ineligible for intensive chemotherapy; however, several studies suggest many older patients benefit from intensive chemotherapy with a curative intent, and a more holistic approach to determining eligibility for intensive treatment is recommended. Intensive strategies have also been expanded to include novel chemotherapy designs and chemotherapy in combination with targeted agents for patients with certain disease characteristics, which may permit more personalized treatment decisions. Intensive chemotherapy continues to play a pivotal role for the management of many AML patients and can offer the best chance of long-term remission, especially when followed by transplantation

granulocyte transfusions a critical reappraisal

Granulocyte transfusions (GTs) are seldom used as a life-saving therapy for neutropenic patients with severe infections. Despite compelling evidence of GT efficacy in retrospective and prospective case series, no study has been successful in demonstrating a definite advantage for recipients in controlled clinical trials. This review critically revises some aspects emerging from past experience that might have weakened the evidence of GT benefits. Some specific issues relevant to the efficacy of this therapeutic approach, such as primary infection, delivered doses and schedules, and immunologic effects of GTs, are discussed. Importantly, the awareness of biologic effects accompanying the transfusion of neutrophils might support their use at standardized doses and may definitely convey significant advantages to the recipient patients

Clinical Aspects and Therapy of Sporadic Burkitt Lymphoma

Burkitt’s lymphoma is a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants, sharing many morphologic and immunophenotypic features. It is characterized by a high proliferation rate and propensity for extranodal sites such as gastrointestinal tract and reproductive organs. Brief-duration, high-intensity chemotherapy regimens including aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease in the sporadic form, with very high complete remission rate and overall survival in adults. Although Burkitt’s lymphoma is extremely chemosensitive, biologically targeted therapies should be developed, because current treatment options are suboptimal for patients with poor prognostic features or with relapsed disease

Mastocytosis: One Word for Different Diseases

Abstract Mastocytosis is a neoplastic disease originating from tissue infiltration by transformed mast cells. The diagnosis requires a high grade of suspicion due to the large variety of presenting symptoms. The World Health Organization classification recognizes localized (cutaneous) and systemic forms of the disease, with these forms showing different degrees of aggressiveness. Mastocytosis is often a multiorgan disease, and its correct management requires a multidisciplinary team of experienced consultants to provide overall patient care. Bone marrow evaluation by molecular analyses, skeleton X-ray and abdominal scan together with allergologic and dermatologic evaluation constitute the essential diagnostic work-up for adult patients with mastocytosis. As clinical situations vary, treatment options range from the use of drugs to treat the symptoms, such as anti-H1 receptors and steroids, to UV irradiation, which is overwhelmingly used in patients with cutaneous mastocytosis (CM) or indolent systemic mastocytosis, to cytoreductive treatment to control life-threatening symptoms or organ damage in the more aggressive forms of the disease. Prognosis also widely differs among patients diagnosed with mastocytosis, with the spectrum ranging from an almost normal life expectancy for those with CM and to less than 1-year median overall survival for those with mast cell leukemia

Prophylaxis and treatment of invasive fungal infections in hematological patients

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it's possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole)

INVASIVE FUNGAL INFECTIONS IN PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISORDERS IN THE ERA OF TARGET DRUGS

This review summarizes the more recent evidence about epidemiology and risk factors for invasive fungal infections (IFI) in patients affected by Chronic Lymphocytic Leukemia (CLL), indolent Non Hodgkin Lymphoma (iNHL) and Multiple Myeloma (MM). Despite advances in the prognosis and treatment of hematological malignancies in recent years, susceptibility to infection remains a significant challenge to patient care. A large amount of data regarding patients with acute leukemia has been published while little information is available on the incidence of IFI in chronic lymphoproliferative disorders (CLD). New drugs are now available for treatment of lymphoproliferative disorders which may cause suppression of humoral immunity, cellular immunity, and deficiency of white blood cells, increasing the risk for infections which remain the leading cause of mortality in these patients

Reply to the letter to the editor “chronic disseminated candidiasis” by Kenneth Rolston

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COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

COVID-19; Epidemiology; Hematological malignanciesCOVID-19; Epidemiologia; Neoplàsies hematològiques malignesCOVID-19; Epidemiología; Neoplasias hematológicas malignasBackground Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020 Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.Open access funding provided by Projekt DEA