Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 59
Filter
5.
Br J Haematol ; 197(6): 691-696, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1714140

ABSTRACT

Data on the response to the COVID-19 vaccine in patients with myeloid malignancy, who are at severe risk in case of infection, have not emerged. In a study of 69 patients with myeloid malignancies, including 46 patients with acute myeloid leukaemia (AML) and 23 patients with myelodysplastic syndrome (MDS), anti-spike SARS-CoV-2 antibody titres were measured 3 months after the second mRNA-based vaccination. Seroconversion rates for AML and MDS were 94.7% and 100% respectively, with no significant difference from healthy controls (HCs). Patients with MDS showed a significantly lower antibody titre than that in HCs or AML patients. In AML patients, the antibody titres were comparable to those in HCs when treatment was completed, but lower in patients under maintenance therapy. The response to COVID-19 vaccine appears to be related to disease and treatment status. Patients with myeloid malignancies may be more responsive to vaccines than patients with lymphoid malignancies.


Subject(s)
COVID-19 , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Myeloproliferative Disorders , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , RNA, Messenger , SARS-CoV-2 , Vaccination
8.
FEBS J ; 288(21): 6087-6094, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526365

ABSTRACT

Anthony Letai is Professor in Medicine at Harvard Medical School and Dana Farber Cancer Institute, and President of The Society for Functional Precision Medicine. Among Tony's scientific achievements, work from his lab contributed toward the FDA approval of Venetoclax combination treatment for adult acute myeloid leukemia (AML) patients. Moreover, his studies on cancer cell death have led to the development of BH3 profiling, an assay that allows for the definition of how close a cell is to the threshold required to commit to apoptosis, which can be used to improve clinical outcomes for cancer patients. In this interview, Tony relays the story behind some of his scientific breakthroughs, discusses the importance of function when designing targeted cancer therapies, gives an overview of BH3 profiling and its application to cancer therapy, and recalls the key events and collaborations that drove his successful research career.


Subject(s)
Precision Medicine/methods , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Humans , Leukemia, Myeloid, Acute/drug therapy , Sulfonamides/therapeutic use
9.
Elife ; 102021 08 05.
Article in English | MEDLINE | ID: covidwho-1513039

ABSTRACT

For an emerging disease like COVID-19, systems immunology tools may quickly identify and quantitatively characterize cells associated with disease progression or clinical response. With repeated sampling, immune monitoring creates a real-time portrait of the cells reacting to a novel virus before disease-specific knowledge and tools are established. However, single cell analysis tools can struggle to reveal rare cells that are under 0.1% of the population. Here, the machine learning workflow Tracking Responders EXpanding (T-REX) was created to identify changes in both rare and common cells across human immune monitoring settings. T-REX identified cells with highly similar phenotypes that localized to hotspots of significant change during rhinovirus and SARS-CoV-2 infections. Specialized MHCII tetramer reagents that mark rhinovirus-specific CD4+ cells were left out during analysis and then used to test whether T-REX identified biologically significant cells. T-REX identified rhinovirus-specific CD4+ T cells based on phenotypically homogeneous cells expanding by ≥95% following infection. T-REX successfully identified hotspots of virus-specific T cells by comparing infection (day 7) to either pre-infection (day 0) or post-infection (day 28) samples. Plotting the direction and degree of change for each individual donor provided a useful summary view and revealed patterns of immune system behavior across immune monitoring settings. For example, the magnitude and direction of change in some COVID-19 patients was comparable to blast crisis acute myeloid leukemia patients undergoing a complete response to chemotherapy. Other COVID-19 patients instead displayed an immune trajectory like that seen in rhinovirus infection or checkpoint inhibitor therapy for melanoma. The T-REX algorithm thus rapidly identifies and characterizes mechanistically significant cells and places emerging diseases into a systems immunology context for comparison to well-studied immune changes.


Subject(s)
COVID-19/immunology , Leukemia, Myeloid, Acute/immunology , Melanoma/immunology , Picornaviridae Infections/immunology , Unsupervised Machine Learning , Adolescent , Adult , Algorithms , CD4-Positive T-Lymphocytes/immunology , Humans , Leukemia, Myeloid, Acute/drug therapy , Melanoma/drug therapy , Neoplasms , Rhinovirus/isolation & purification , SARS-CoV-2/isolation & purification , Young Adult
10.
Rinsho Ketsueki ; 62(10): 1474-1481, 2021.
Article in Japanese | MEDLINE | ID: covidwho-1502772

ABSTRACT

BACKGROUND: With the global spread of coronavirus disease 2019 (COVID-19), patients with cancer may be at a higher risk of suffering from COVID-19. Although patients with hematological malignancy (HM) are reported to have a higher risk of severe COVID-19 compared with those with solid cancer, the effects of treatment for HM on COVID-19 severity have not been fully elucidated. METHODS: We retrospectively analyzed the risk factors, including number and timing of chemotherapeutic regimens for HM, for COVID-19 severity in 17 patients with HM, who had developed nosocomial COVID-19 in our department, by dividing them into two groups; a severe group (N=7) and a non-severe group (N=10). RESULTS: The overall mortality rate was 47%, and mortality in the severe group was significantly higher than that in the non-severe group (odds ratio [OR], 18.44; 95% confidence interval [CI], 1.27-1223.17, P=0.02). Univariate analysis identified two or more chemotherapeutic regimens for HM (OR, 17.34; 95%CI, 1.15-1165.33, P=0.03) and a low hemoglobin level (P=0.02) as significant risk factors for COVID-19 severity. However, a history of chemotherapy for HM within 3 months prior to the onset of COVID-19 was not a significant risk factor (P=0.54). CONCLUSION: A history of multiple chemotherapeutic regimens in patients with HM may be a risk factor for COVID-19 severity, and physicians should be aware of this.


Subject(s)
COVID-19 , Cross Infection , Hematologic Neoplasms , Leukemia, Myeloid, Acute , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Humans , Retrospective Studies , Risk Factors , SARS-CoV-2
11.
Hematology ; 26(1): 870-873, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1493499

ABSTRACT

BACKGROUND: COVID-19 viral pandemic caused many mortalities in cancer patients especially those with hematological malignancies. The immunological response to COVID-19 infection is responsible for the outcome of cases whether mild, severe or critical. CASE PRESENTATION: Two cases presented with moderate COVID-19 viral infection, concomitant with acute myeloid leukemia and T acute lymphoblastic leukemia, respectively. Surprisingly, after the administration of COVID-19 supportive therapy, the cases showed disease remission after a follow-up period of 12 and 5 months, respectively. Additionally, the blast cells dropped to only 3% and 0% in the bone marrow aspirates of those two cases, respectively, after it was 30% in both cases at diagnosis. CONCLUSION: The immune response that emerged against COVID-19 infection could potentially produce anti-tumor immunity in some patients, or the virus may act as an oncolytic virus. However, further investigations are required to explain this phenomenon, which may help in finding a possible new targeted therapy for these cases.


Subject(s)
COVID-19/complications , Leukemia, Myeloid, Acute/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Adult , COVID-19/therapy , Disease Management , Female , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Remission Induction , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
12.
Pediatr Transplant ; 26(2): e14179, 2022 03.
Article in English | MEDLINE | ID: covidwho-1488242

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic brought challenges to all areas of medicine. In pediatric bone marrow transplant (BMT), one of the biggest challenges was determining how and when to transplant patients infected with SARS-CoV-2 while mitigating the risks of COVID-related complications. METHODS: Our joint adult and pediatric BMT program developed protocols for performing BMT during the pandemic, including guidelines for screening and isolation. For patients who tested positive for SARS-CoV-2, the general recommendation was to delay BMT for at least 14 days from the start of infection and until symptoms improved and the patient twice tested negative by polymerase chain reaction (PCR). However, delaying BMT in patients with malignancy increases the risk of relapse. RESULTS: We opted to transplant two SARS-CoV-2 persistently PCR positive patients with leukemia at high risk of relapse. One patient passed away early post-BMT of a transplant-related complication. The other patient is currently in remission and doing well. CONCLUSION: These cases demonstrate that when the risk associated with delaying BMT is high, it may be reasonable to proceed to transplant in pediatric leukemia patients infected with SARS-CoV-2.


Subject(s)
COVID-19/complications , Hematopoietic Stem Cell Transplantation/methods , Leukemia, B-Cell/therapy , Leukemia, Myeloid, Acute/therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , COVID-19/diagnosis , Fatal Outcome , Female , Humans , Infant , Leukemia, B-Cell/complications , Leukemia, Myeloid, Acute/complications , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications , Time-to-Treatment
13.
Eur J Haematol ; 108(1): 61-72, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1476174

ABSTRACT

During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.


Subject(s)
Antilymphocyte Serum/therapeutic use , Cryopreservation/methods , Cyclophosphamide/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/cytology , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Aged , COVID-19/epidemiology , Female , Graft vs Host Disease , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Transplantation Conditioning , Treatment Outcome , Young Adult
15.
Int J Hematol ; 115(1): 61-68, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1432631

ABSTRACT

BACKGROUND: "Hospital-at-home" (HAH) programs have been shown to optimize resource utilization, shorten hospitalization and prevent nosocomial infection. METHODS: We retrospectively analysed data regarding implementation of an HAH unit for caring patients with hematological malignancies in our center, during the COVID-19 pandemic. RESULTS: Between January and November 2020, 105 patients were treated in the HAH unit for a total of 204 episodes. Nine patients with multiple myeloma (MM) received autologous HSCT (auto-HSCT). Three patients with acute myeloid leukemia (AML) received consolidation therapy, 32 patients underwent clinical and analytical monitoring, 20 were transplant recipients early discharged (5 auto-HSCT and 15 allo-HSCT) and 2 had received CART cells therapy. Azacitidine, bortezomib and carfilzomib were administered at home to 54 patients with AML, myelodysplastic syndrome (MDS) or MM. A median of 17 (IQR 13-19) days of admission per patient and a total of 239 visits to the Hematology day-care hospital were avoided. Overall, 28 patients (14% of all episodes) needed admission to the hospital, 4 of them due to COVID-19. CONCLUSIONS: Implementation of a Hematology HAH unit was feasible and safe, and provided thorough advanced care to a high-risk population. Advanced care-at-home strategies can be crucial during times of COVID-19 to minimize treatment interruptions and reduce the risk of cross-infections.


Subject(s)
COVID-19 , Continuity of Patient Care , Hematologic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Disease Management , Feasibility Studies , Female , Hematopoietic Stem Cell Transplantation , Hospitalization , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Multiple Myeloma/therapy , Myelodysplastic Syndromes/therapy , Retrospective Studies , Transplantation, Autologous , Young Adult
16.
In Vivo ; 35(5): 2951-2955, 2021.
Article in English | MEDLINE | ID: covidwho-1436484

ABSTRACT

BACKGROUND/AIM: We present the case of a 19-year-old male patient diagnosed concomitantly with extensive thromboses (including two intra-cardiac masses and Budd-Chiari syndrome), as well as acute myeloid leukemia. This necessitated prompt deployment of a monitoring and treatment strategy which included twice-daily blood count assessment, multiple platelet transfusions and anti-coagulation therapy with dose-adjustment per blood count during both induction and consolidation chemotherapy. Multiple factors are believed to contribute to the development of thrombosis in acute leukemia such as diffuse intravascular coagulation, cytokine release and chemotherapy. CASE REPORT: Our patient presented early on in the COVID-19 pandemic, delaying his seeking out medical treatment and we suspect this to have contributed to his 'catastrophic' thrombotic presentation. Well-structured guidelines to help clinicians manage these patients are lacking, and most data are from retrospective analyses or case reports. Our patient continued full-dose anticoagulant therapy until successfully undergoing allogeneic stem cell transplant. The thrombi eventually diminished in size, and the patient was not diagnosed with any further thrombotic events. CONCLUSION: Our case highlights the feasibility of intensive monitoring and provision of platelet transfusion as necessary in order to safely administer low molecular weight heparin from the outset of chemotherapy.


Subject(s)
COVID-19 , Leukemia, Myeloid, Acute , Thrombosis , Adult , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/diagnosis , Male , Pandemics , Retrospective Studies , SARS-CoV-2 , Thrombosis/diagnosis , Thrombosis/etiology , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL