scholarly journals SARS-CoV-2 precipitated Kasabach-Merritt syndrome in a child with Kaposiform Hemangiendothelioma and acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Vanessa Zarate ◽  
Alejandra Cahuata ◽  
Roxana Diaz ◽  
Kenny Chonlon ◽  
Giancarlo Alvarado-Gamarra ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Inflammatory Response ◽  
Direct Effect ◽  
Vascular Injury ◽  
Lymphoblastic Leukemia ◽  
Therapeutic Strategies ◽  
Vascular Involvement ◽  
Clotting Factors ◽  
Intestinal Involvement ◽  
Host Inflammatory Response

Kaposiform hemangiendothelioma usually occurs in children under two years of age and develops thrombocytopenia secondary to sequestration of platelets within (Kasabach-Merritt phenomenon) and is complicated by secondary consumption of fibrinogen and clotting factors. SARS-CoV-2 produces cutaneous endothelitis as a direct effect of the presence of the virus and the host inflammatory response. We describe an 8-month-old boy with leukemia and SARS-CoV-2 infection who developed Kasabach-Merritt phenomenon, coagulopathy, and intestinal involvement. Given the emerging evidence of endothelial and vascular involvement in COVID-19, the development of tests to detect vascular injury may be critical to guide the use of new therapeutic strategies.

scholarly journals SARS-CoV-2 precipitated Kasabach-Merritt syndrome in a child with angioma infantile and acute lymphoblastic leukemia: Case Report

2021 ◽  
Vol 14 (3) ◽  
pp. 387-389
Author(s):  
Vanessa Zarate ◽  
Alejandra Cahuata ◽  
Roxana Díaz ◽  
Giancarlo Alvarado-Gamarra ◽  
Kenny Chonlon ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Therapeutic Strategies ◽  
Vascular Lesions ◽  
Vascular Involvement ◽  
Rt Pcr ◽  
Ischemic Necrosis ◽  
Hematologic Tests ◽  
Atypical Form ◽  
Intestinal Involvement ◽  
Tract Involvement

Background: We describe an 8-month-old boy with leukemia and SARS-CoV-2 infection who developed Kasabach-Merritt phenomenon. He had a positive SARS-COV-2 RT-PCR sample. Hematologic tests showed coagulopathy and intestinal involvement. She was managed in emergency receiving transfusion support and in hospitalization with social isolation measures, she started propanolol and corticotherapy as initial treatment of infantile angiomas. She presented with symptoms of intestinal obstruction and underwent surgery and evidence of hemorrhagic infarction with foci of intestinal ischemic necrosis, ending in ileostomy. We tried to understand a pathophysiological explanation of the dermatologic and gastrointestinal tract involvement by the virus and the atypical form of COVID-19. Given the emerging evidence of endothelial and vascular involvement in COVID-19, the development of tests to detect vascular lesions may be critical to guide the use of new therapeutic strategies.

scholarly journals Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection

2016 ◽  
Vol 35 (5) ◽  
pp. 2699-2706 ◽  
Author(s):  
E. PÉREZ-FIGUEROA ◽  
M. SÁNCHEZ-CUAXOSPA ◽  
K.A. MARTÍNEZ-SOTO ◽  
N. SÁNCHEZ-ZAUCO ◽  
A. MEDINA-SANSÓN ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Inflammatory Response ◽  
Lymphoblastic Leukemia ◽  
Polarization Profile ◽  
Strong Inflammatory Response ◽  
Th1 Polarization

scholarly journals Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Charlotte E. J. Downes ◽  
Barbara J. McClure ◽  
John B. Bruning ◽  
Elyse Page ◽  
James Breen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Cell Model ◽  
Lymphoblastic Leukemia ◽  
High Risk Patient ◽  
Therapeutic Strategies ◽  
Drug Binding ◽  
Type I ◽  
Jak Inhibitors

AbstractRuxolitinib (rux) Phase II clinical trials are underway for the treatment of high-risk JAK2-rearranged (JAK2r) B-cell acute lymphoblastic leukemia (B-ALL). Treatment resistance to targeted inhibitors in other settings is common; elucidating potential mechanisms of rux resistance in JAK2r B-ALL will enable development of therapeutic strategies to overcome or avert resistance. We generated a murine pro-B cell model of ATF7IP-JAK2 with acquired resistance to multiple type-I JAK inhibitors. Resistance was associated with mutations within the JAK2 ATP/rux binding site, including a JAK2 p.G993A mutation. Using in vitro models of JAK2r B-ALL, JAK2 p.G993A conferred resistance to six type-I JAK inhibitors and the type-II JAK inhibitor, CHZ-868. Using computational modeling, we postulate that JAK2 p.G993A enabled JAK2 activation in the presence of drug binding through a unique resistance mechanism that modulates the mobility of the conserved JAK2 activation loop. This study highlights the importance of monitoring mutation emergence and may inform future drug design and the development of therapeutic strategies for this high-risk patient cohort.

scholarly journals Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Silvia Jiménez-Morales ◽  
Ivan Sammir Aranda-Uribe ◽  
Carlos Jhovani Pérez-Amado ◽  
Julian Ramírez-Bello ◽  
Alfredo Hidalgo-Miranda
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Immune Evasion ◽  
Tumor Response ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Leukemia Cells ◽  
Biological Features ◽  
Novel Therapeutic Strategies

Acute lymphoblastic leukemia (ALL) is a malignancy with high heterogeneity in its biological features and treatments. Although the overall survival (OS) of patients with ALL has recently improved considerably, owing to the application of conventional chemo-therapeutic agents, approximately 20% of the pediatric cases and 40–50% of the adult patients relapse during and after the treatment period. The potential mechanisms that cause relapse involve clonal evolution, innate and acquired chemoresistance, and the ability of ALL cells to escape the immune-suppressive tumor response. Currently, immunotherapy in combination with conventional treatment is used to enhance the immune response against tumor cells, thereby significantly improving the OS in patients with ALL. Therefore, understanding the mechanisms of immune evasion by leukemia cells could be useful for developing novel therapeutic strategies.

scholarly journals Preclinical efficacy of humanized, non–FcγR-binding anti-CD3 antibodies in T-cell acute lymphoblastic leukemia

Blood ◽  
2020 ◽  
Vol 136 (11) ◽  
pp. 1298-1302 ◽  
Author(s):  
Christine Tran Quang ◽  
Benedetta Zaniboni ◽  
Romain Humeau ◽  
Etienne Lengliné ◽  
Marie Emilie Dourthe ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Therapeutic Option ◽  
Lymphoblastic Leukemia ◽  
Therapeutic Strategies ◽  
Fcγ Receptor ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Novel Therapeutic Strategies ◽  
Cure Rates ◽  
Pdx Models

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for ∼20% of ALL cases. Intensive chemotherapy regimens result in cure rates >85% in children and <50% in adults, warranting a search of novel therapeutic strategies. Although immune-based therapies have tremendously improved the treatment of B-ALL and other B-cell malignancies, they are not yet available for T-ALL. We report here that humanized, non–Fcγ receptor (FcγR)–binding monoclonal antibodies (mAbs) to CD3 have antileukemic properties in xenograft (PDX) models of CD3+ T-ALL, resulting in prolonged host survival. We also report that these antibodies cooperate with chemotherapy to enhance antileukemic effects and host survival. Because these antibodies show only minor, manageable adverse effects in humans, they offer a new therapeutic option for the treatment of T-ALL. Our results also show that the antileukemic properties of anti-CD3 mAbs are largely independent of FcγR-mediated pathways in T-ALL PDXs.

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