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Peripheral Blood and Bone Marrow
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Fermina Maria Mazzella, Gerardo Perrotta
Because specific chromosomal abnormalities are associated with certain hematologic disorders, such as t(15 : 17) for acute promyelocytic leukemia, cytogenetic analysis may aid in the classification these disease processes. Cytogenetic studies can also be used to monitor remissions and relapses, and to distinguish between donor and recipient cells in bone marrow transplantation. New and exciting methods, particularly fluorescent in-situ hybridization (FISH), have been developed which permit chromosomal analysis on either metaphase or interphase cells, as well as paraffin-embedded tissue. Fluorescent-labeled probes unique to many chromosomes and fusion genes, such as bcr/abl in chronic myelogenous leukemia (CML), are already available.
Disseminated Intravascular Coagulation (Dic) And Related Syndromes
Published in Genesio Murano, Rodger L. Bick, Basic Concepts of Hemostasis and Thrombosis, 2019
Most patients with disseminated malignancy have some laboratory evidence of DIC, however many never develop clinical manifestations. Malignancy represents a special situation in that DIC may be acute, subacute, or chronic, and may be manifest as local thromboses, diffuse thromboses, minor hemorrhage, diffuse hemorrhage, or any combination.14 The acute leukemias are also associated with DIC. This was first noted in acute promyelocytic leukemia. The release of procoagulant enzymes from promyelocytes appears responsible for triggering the clotting sequence.15, 16 In many instances, the initiation of cytotoxic chemotherapy may initiate or significantly enhance the disseminated intravascular clotting process. For this reason, some have advocated the use of prophylactic heparin or mini-heparin before initiating cytotoxic chemotherapy.17
Role of Procoagulant Activity in Neoplastic Disease
Published in Gary A. Levy, Edward H. Cole, Procoagulant Activity in Health and Disease, 2019
Richard L. Edwards, Frederick R. Rickles
Although as early as 1954 it was suspected that human leukemia cells possessed substantial thromboplastic activity,40 it was not until 1973 that Gralnick and Abrell identified TF-like activity in the buffy coat of patients with progranulocytic leukemia.41 Subsequently, Goualt-Heilman and associates demonstrated that the PCA of peripheral blood cells from some patients with acute progranulocytic leukemia (APL) was neutralized by a polyclonal antibody raised against brain TF.42 Further evidence for the potential role of TF in the activation of coagulation in leukemia is provided by the demonstration of TF gene expression in some but not all leukemic myeloblasts.43 It has long been recognized that patients with acute promyelocytic leukemia have an unusually high incidence of bleeding and/or thrombotic complications. This coagulopathy has generally been attributed to activation of systemic blood coagulation by tumor cell-derived TF with resultant DIC,44 which has been supported by several recent studies in which a correlation was demonstrated between TF levels and the presence of DIC.45,46
Clinical and molecular characteristics of acute myeloid leukemia and the dismal prognosis of TP53 mutations in a real-world setting
Published in Hematology, 2023
Hong Liu, Yuye Shi, Shandong Tao, Yunjie Li, Chunling Wang, Liang Yu
We retrospectively analyzed 326 patients with newly diagnosed AML and available cytogenetic and molecular data, who received treatment at The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University between October 2015 and June 2021. AML was diagnosed according to the 2016 revision of the WHO classification of myeloid neoplasms and acute leukemia [17]. Patients with acute promyelocytic leukemia and patients lacking baseline mutation data were excluded. The clinical characteristics of the patients were collected, including age, sex, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), cytogenetic and molecular abnormalities, initial and subsequent treatment strategies, and overall survival (OS). Bone marrow examination was performed before each consolidation chemotherapy or when the disease condition changed. All the patients provided written informed consent. The study was approved by the relevant ethics committee and was performed in accordance with the Declaration of Helsinki.
Acute myeloid leukemia: challenges for diagnosis and treatment in Latin America
Published in Hematology, 2023
Andrés Gómez-De León, Roberta Demichelis-Gómez, Abel da Costa-Neto, David Gómez-Almaguer, Eduardo Magalhães Rego
Acute myeloid leukemia (AML), a neoplasm derived from the malignant transformation and expansion of myeloid precursors, is common around the world. Across the age spectrum, older adults are the most frequent group affected, with a median age at diagnosis of 65 years in North America and Europe [1–3]. Epidemiological differences in Latin-America (LA) compared to high-income countries (HICs) have been reported. For instance, a younger age at diagnosis ranging from 40–47 years due to our overall younger population, and a higher prevalence of acute promyelocytic leukemia (APL) in comparison to non-APL subtypes [4–6]. Furthermore, differences in access to treatment alternatives for this disease changes the way AML should be approached according to geographic regions and socioeconomic contexts. In this review, we will summarize the diagnosis and treatment of AML through the lens of hematologists working in LA as a reflection of other low and middle-income countries (LMICs) and disadvantaged populations in HICs and focus on specific challenges and their potential solutions faced in these regions of the world.
High-dose hydroxyurea with differentiating agents for treating ultra-high-risk acute promyelocytic leukemia in resource-challenged settings
Published in Acta Oncologica, 2022
Charanpreet Singh, Sarthak Wadhera, Uday Yanamandra, Parathan Karunakaran, Nishant Jindal, Saloni Rani Kumar, Neha Saini, Aditya Jandial, Arihant Jain, Chandan Das, Gaurav Prakash, Alka Khadwal, Shano Naseem, Reena Das, Neelam Varma, Subhash Varma, Pankaj Malhotra, Deepesh Lad
There has been a paradigm shift in treating acute promyelocytic leukemia (APL) in the past few decades. Differentiating agents, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), now form the backbone of treatment for APL. Low and intermediate-risk APL is associated with excellent long-term outcomes when treated with ATO and ATRA. However, the treatment of high-risk APL remains debatable due to the high early mortality from respiratory failure due to differentiation syndrome and severe bleeding due to disseminated intravascular coagulation [1]. Therefore, the current recommendations include adding anthracycline or gemtuzumab ozogamicin (GO) to ATO + ATRA to control leukocytosis in high-risk APL [2]. Few studies have reported treating high-risk APL with only ATO + ATRA. One pilot study reported treating 20 high-risk APL patients with oral ATO + ATRA without anthracycline/GO, though cytarabine was used for cytoreduction in 80% of patients [3]. Vaid et al. recently reported using ATO + ATRA to treat a subset (n = 13/21) of high-risk APL (WBC 10–50 × 109/L) due to the presence of infections at presentation. This cohort had a mortality rate of 43% [4]. Even with anthracyclines, the mortality rate is 23–34% in the intention-to-treat analysis of high-risk APL patients in India [4–7]. GO is unavailable in India. Our center protocol includes ATO + ATRA for all risk classes with additional hydroxyurea as cytoreductive therapy in high-risk APL patients [8]. Here we describe the efficacy and safety of high-dose hydroxyurea for cytoreduction in ultra-high-risk APL [9].