scholarly journals Hemophagocytic lymphohistiocytosis as an unexpected complication of Venetoclax+Azacitidine in Acute Myeloid Leukemia

2021 ◽  
Vol 9 (1) ◽  
pp. 17-19
Author(s):  
Ovilla-Martinez Roberto ◽  
Perez-Lozano Uendy ◽  
Cota-Rangel Xochitl ◽  
Baez-Islas Pamela
Keyword(s):  
Acute Myeloid Leukemia ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Myeloid Leukemia ◽  
Early Recognition ◽  
Case Series ◽  
Lymphocytic Leukemia ◽  
Acute Phase Reactants ◽  
Hematologic Disorder ◽  
Serious Infections ◽  
Acute Myeloid

Background: Venetoclax is a drug that targets BCL-2 protein in cancer cells, first approved for chronic lymphocytic leukemia, this drug has showed efficacy also in acute myeloid leukemia in non-intense chemotherapy candidates in combination with hypomethylating agents as azacitidine and decitabine. This scheme has shown efficiency in acute myeloid leukemia reporting overall response rate (CR) in 61% in untreated elderly patients combined with azacitidine or decitabine. Febrile neutropenia was reported in 30%, thrombocytopenia in 47%, and serious infections in 33%. Hemophagocytic lymphohistiocytosis (HLH) is an uncommon hematologic disorder caused by a proinflammatory state manifested by cytopenias and elevation of acute phase reactants; it is a severe complication of some diseases and to our knowledge it has never been reported secondary to venetoclax plus azacitidine. Early treatment is fundamental for success in HLH. Case series: Three cases of HLH secondary to venetoclax plus azacitidine have appeared in our medical group in patients treated for acute myeloid leukemia. One elderly woman and elderly men with previously untreated acute myeloid leukemia presented HLH with laboratory and bone marrow findings, both responded to dexamethasone plus ruxolitinib. The third case was documented in a male diagnosed with blast phase chronic myeloid leukemia who also responded to dexamethasone plus ruxolitinib. No patient died from HLH. Conclusion: Here we report three cases of patients with HLH after the treatment with azacitidine plus venetoclax. We suspect that the great effect of venetoclax in synergy with azacitidine can liberate enough proinflammatory cytokines in the medullar niche to induce HLH. Early recognition is vital for soon treatment and successful management of this potential complication.

scholarly journals Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiang Zhang ◽  
Jiejing Qian ◽  
Huafeng Wang ◽  
Yungui Wang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Underlying Mechanism ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Dominant Mutation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

scholarly journals A Case of Acute Myeloid Leukemia Concurrent With Untreated Chronic Lymphocytic Leukemia

2017 ◽  
Vol 37 (4) ◽  
pp. 336-338
Author(s):  
Hye-Young Lee ◽  
Chan-Jeoung Park ◽  
Enkyung You ◽  
Young-Uk Cho ◽  
Seongsoo Jang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Chronic Lymphocytic Leukemia ◽  
Myeloid Leukemia ◽  
Lymphocytic Leukemia ◽  
Acute Myeloid

scholarly journals Hemophagocytic Lymphohistiocytosis Syndrome As Presenting Sign For Acute Monocytic Leukaemia- A Case Report.

2020 ◽  
Vol 7 (08) ◽  
pp. 4918-4924
Author(s):  
Gal Sahaf Levin ◽  
Gida Ayada ◽  
Moshe Yeshurun ◽  
Oleg Rogach ◽  
Shaul Lev
Keyword(s):  
Acute Myeloid Leukemia ◽  
Organ Failure ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Myeloid Leukemia ◽  
Case Reports ◽  
Transitional Cell ◽  
Interleukin 2 ◽  
Clinical Manifestations ◽  
Multi Organ Failure ◽  
Acute Myeloid

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare aggressive syndrome of excessive immune activation. Clinical manifestations of this syndrome mimic various other clinical conditions making the diagnosis harder to achieve. These manifestations are believed to be a result of cytokine storm which leads, eventually, to a multi-organ failure and eventually death. The latter two might be prevented if HLH was diagnosed early. HLH is classified into primary consist of monogenic disorders and secondary occurs as a complication in various settings such as infection, autoimmune disease, and malignancy. In hematologic malignancies, HLH is classically associated with specific entities, mainly, lymphoma or induced by treatment-related infections. Acute myeloid leukemia, on the other hand, is less common trigger with only few case reports.   Case presentation: An 83-years-old, 5 years free of transitional cell man, presented with unstable atrial fibrillation was intubated and shortly after that he developed a multi-organ failure. Bicytopenia and a high level of ferritin aroused a clinical suspicion of HLH syndrome. Further evaluation revealed high levels of soluble interleukin 2 receptors and no activity of natural killers cells. A bone marrow was performed and it did not show phagocytosis, however, acute myeloid leukemia (AML) was diagnosed. AML was suggested to be associated with chemotherapy that our patient received 5 years earlier.   Conclusion: Hemophagocytic lymphohistiocytosis can be present as a multi-organ failure requiring a high index of suspicion. Chemotherapy related-AML can be a trigger for HLH. 

scholarly journals Mesenchymal Stem Cells (MSCs) Intensify the Impact of KIR Ligand-Mismatching on Acute Graft-Versus-Host Disease Post HSCT in Patients with Acute Myeloid Leukemia but Not with Acute Lymphocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-42
Author(s):  
Yu Zhang ◽  
Shaozhen Chen ◽  
Jinhua Ren ◽  
Xiaofeng Luo ◽  
Zhizhe Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Mesenchymal Stem Cells ◽  
Graft Versus Host Disease ◽  
Myeloid Leukemia ◽  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Acute Myeloid

Objectives: Mesenchymal stem cells (MSCs) and killer cell immunoglobulin-like receptor (KIR) ligand-mismatch, which can trigger the alloreactivity of natural killer (NK) cells, have been shown to be protective for severe acute and chronic graft-versus-host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there are no prospective or retrospective studies exploring their relationship. Here, we investigated the potential influence of KIR matching, MSCs and their coaction on GVHD prophylaxis, overall survival (OS) and relapse rate (RR) of allo-HSCT. Methods: Data from 154 patients with acute myeloid and lymphocytic leukemia treated with allo-HSCT between May 2015 and May 2020 in the transplantation unit of the Fujian Medical University Union Hospital were retrospectively analyzed. The cohort included 93 male patients (60.3%) and 61 female (39.7%), with a median age of 24 years (1-59 years), 104 cases of acute myeloid leukemia (AML; 67.5%) and 50 cases with acute lymphocytic leukemia (ALL; 32.5%). Eighty-one patients (52.6%) underwent MSCs infusion on day+1. The sources of MSCs were human placenta or human bone marrow. MSCs infusion dose ranged from 0.5 to 3x106/kg of recipient weight. KIR genotyping was performed by the PCR-SSO method. The amplicons were quantified on the Luminex 200 flow analyzer and analyzed using the Quick-Type for Lifecodes software for generating KIR data. Cox proportional hazards model and Kaplan-Meier survival curves were used for analysis. Results: At the time of transplantation, 65 cases (42.2%) were in remission, while 89 (57.8%) had active disease. aGVHD occurred in 31 patients (20.1%) and recurrence arose in 21 patients (13.6%), but no significant cGVHD was observed. After adjusting for age, disease-risk, HLA-match, donor gender, conditioning regimen intensity and type of post-grafting GVHD prophylaxis, Cox regression analysis revealed that KIR ligand-matching was associated with an increased risk of aGVHD compared to KIR ligand-mismatching (p=0.023) in AML patients, but KIR ligand-mismatching had no significant effect on aGVHD in ALL patients, and on OS and RR in both AML and ALL patients. MSCs was associated with much lower recurrence rate (RR) (p=0.049), even when the recipients were not in remission at the time of HSCT. Furthermore, MSCs reduced the incidence of aGVHD in both AML and ALL patients, although it did not reach statistical significance (p=0.19). The combination of KIR ligand-mismatching and MSCs infusion significantly suppressed aGVHD occurrence in AML patients (p=0.033). More importantly, MSCs infusion intensified the suppression effect of KIR ligand-mismatching on aGVHD in AML patients (p=0.047). In the KIR ligand-mismatch group, the incidence of aGVHD was 10.3% when patients received MSCs, compared to 25.6% in those who did not. However, combining KIR ligand-mismatch and MSCs injection had no significant effect on aGVHD in ALL patients, or on OS and RR in both AML and ALL patients. Conclusions: KIR ligand-mismatch, MSCs infusion and their combination significantly reduced the risk of aGVHD after allo-HSCT in AML patients. It confirms the relationship between MSCs injection and lower RR. These data provide a clinically applicable strategy where co-transplantation with MSCs and triggering of allo-NK cells by KIR ligand-mismatching can ameliorate aGVHD, thus improving allo-HSCT outcome in AML patients. Disclosures No relevant conflicts of interest to declare.

Tonsillitis with Acute Myeloid Leukemia: A Case Series for Caution

2013 ◽  
Vol 92 (4) ◽  
pp. E22-E23 ◽  
Author(s):  
Jagdeep S. Thakur ◽  
N.K. Mohindroo ◽  
D.R. Sharma ◽  
Shobha Mohindroo ◽  
Anamika Thakur
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Case Series ◽  
Acute Myeloid
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