Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 135
Filter
1.
J Pediatr Hematol Oncol ; 44(1): e127-e133, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1608558

ABSTRACT

Data regarding the epidemiologic characteristics and clinical features of pediatric hematologic patients are limited in this corona virus disease 2019 (COVID-19) crisis. We investigated the status of 113 pediatric hematologic patients in Wuhan union hospital during the COVID-19 pandemic from January 23 to March 10, 2020. All the patients had routine blood and biochemical examination, as well as chest computed tomography scans, and the nucleic acid, immunoglobulin G-immunoglobulin M combined antibodies tests for SARS-CoV-2. After admission, all patients were single-room isolated for 5 to 7 days. The results showed that only 1 (0.88%) child with leukemia was confirmed to have SARS-CoV-2 infection and 15 (13.2%) children were considered as suspected cases. Comparing to the nonsuspected patients, the suspected cases had lower white blood cell count, hemoglobin level, neutrophil count, serum calcium ion level and serum albumin concentration, as well as higher levels of C-reactive protein. All the suspected cases were ruled out of SARS-CoV-2 infection by twice negative tests for the virus. Therefore, the incidence of SARS-CoV-2 infection in hematologic malignancy children was low during the COVID-19 pandemic in China. COVID-19 got early detected and the virus spread out in the ward was effectively blocked by increasing test frequency and using single-room isolation for 5 to 7 days after admission.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , Adolescent , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Hematologic Neoplasms/blood , Hospitalization , Humans , Incidence , Infant , Leukemia/blood , Leukemia/complications , Leukocyte Count , Male , Retrospective Studies , SARS-CoV-2/isolation & purification
2.
Lancet Oncol ; 22(6): 765-778, 2021 06.
Article in English | MEDLINE | ID: covidwho-1531901

ABSTRACT

BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer-BioNTech) vaccine in patients with cancer. METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 µg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 µg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Vaccines/immunology , Dose-Response Relationship, Immunologic , Female , Humans , Immunogenicity, Vaccine/immunology , London/epidemiology , Male , Middle Aged , Neoplasms/blood , Neoplasms/complications , Neoplasms/virology , Prospective Studies , SARS-CoV-2 , Wales
3.
Cancer Cell ; 39(8): 1081-1090.e2, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1343145

ABSTRACT

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Neoplasms/complications , Neoplasms/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Host-Pathogen Interactions/immunology , Humans , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Public Health Surveillance , Risk Factors , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
5.
J Pediatr Hematol Oncol ; 44(2): e543-e545, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1270767

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus-2. Patients with hematologic malignancies have been shown to have higher risk of mortality due to COVID-19 than reported in the general adult population. Reports on acute lymphoblastic leukemia and COVID in children are scarce. We present a case of an 11-year-old male patient undergoing treatment for B-cell acute lymphoblastic leukemia with an atypical course of COVID-19. The patient received a positive result of the syndrome coronavirus-2 polymerase chain reaction test performed due to epidemiologic reasons. The chemotherapy was continued since the patient had no clinical signs of COVID-19. The disease started with intensive gastrointestinal bleeding, followed by severe respiratory tract infection over 2 weeks later.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , COVID-19/complications , Gastrointestinal Hemorrhage/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Child , Gastrointestinal Hemorrhage/chemically induced , Humans , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Prognosis
6.
Support Care Cancer ; 29(12): 7591-7599, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1269151

ABSTRACT

BACKGROUND: The COVID-19 pandemic required reevaluation of the therapeutic approach and added emotional stress for patients with hematological malignancies at high risk of contracting the virus. We aimed to evaluate how it affected such patients during the second lockdown in Israel. METHODS: This national survey included Hebrew-speaking patients with hematological malignancy. This included three tools with 28 items of sociodemographic and medical baseline characteristics, management of hematological disease, and evaluation of emotional coping during COVID-19 pandemic; the Hebrew version of the Patient Health Questionnaire 9; and 3 qualitative open-ended questions. Data was analyzed by mixed methods which combined both quantitative and qualitative thematic analyses. RESULTS: Four hundred eight patients responded to the survey. The management of their hematological disease included a decrease in the number of visits to the hematology clinic (37.0%), delay of some treatment schedules (9.1%), and prescription of replacement therapies permitting less visits to the clinic (2.2%). The frequency and intensity of "feeling afraid" regarding COVID-19 infection was increased (mean ± SD: 4 ± 1 to 5 ± 2 in a 1-7 Likert scale), and a high rate of depression was recorded, which appeared to be more evident in patients with chronic myeloid leukemia (CML) (p < 0.001). CONCLUSION: The management of hematological malignancies during pandemics should always take into consideration patients' fears, as well as the development of depression related to isolation and loneliness, in addition to the high risk of severe disease. Patients with CML had a high rate of depression which obviously needs to be managed very carefully during and after the COVID-19 pandemic.


Subject(s)
COVID-19 , Hematologic Neoplasms , Communicable Disease Control , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Humans , Pandemics , SARS-CoV-2
7.
Cancer Med ; 10(13): 4424-4436, 2021 07.
Article in English | MEDLINE | ID: covidwho-1267448

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 leads to COVID-19, the course of which is highly variable and depends on numerous patient-specific risk factors. Patients with tumor diseases are considered to be more susceptible to severe COVID-19; however, they also represent a heterogeneous group of individuals with variable risk. Identifying specific risk factors for a severe course of COVID-19 in patients with cancer is of great importance. METHODS: Patients diagnosed with solid tumors or hematological malignancies and PCR-confirmed SARS-CoV-2 infection were included into the multicentric ADHOK (Arbeitsgemeinschaft der Hämatologen und Onkologen im Krankenhaus e.V.) coronavirus tumor registry. Detailed information about the patients' cancer disease, treatment, and laboratory parameters prior to infection, was collected retrospectively. The outcome of the SARS-CoV-2 infection was graded according to the WHO. RESULTS: A total of 195 patients (68% with solid neoplasms and 32% with hematological malignancies) were included in the registry. Overall, the course of the SARS-CoV-2 infection varied greatly, as 69% of all patients were either asymptomatic or encountered a mild to moderate course, while 23% of the cohort died from COVID-19. In multivariable analysis, preinfection laboratory parameters (determined at least 10 days and a median of 21 days before the first documentation of SARS-CoV-2 infection) significantly correlated with severe course of the disease. Out of these, the absolute neutrophil count prior to infection showed the strongest association with COVID-19-related death. CONCLUSION: The course of COVID-19 in patients with tumor diseases is highly variable. Preinfection laboratory parameters may aid to identify patients at risk for severe COVID-19 at an early stage prior to infection with the virus. German Clinical Trials Register identification: DRKS00023012.


Subject(s)
Biomarkers/blood , COVID-19/mortality , Neoplasms/virology , Neutrophils/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Neoplasms/immunology , Neoplasms/mortality , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
8.
JMIR Res Protoc ; 10(6): e25271, 2021 Jun 01.
Article in English | MEDLINE | ID: covidwho-1268221

ABSTRACT

BACKGROUND: The COVID-19 pandemic has raised unprecedented challenges in the management of patients with cancer and has increased the demands for digital health tools that, for example, could facilitate remote monitoring of patients. Based on this, the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) has recently developed a digital health tool dedicated to patients with hematologic malignancies: the GIMEMA-ALLIANCE platform. OBJECTIVE: The main objectives of this web-based platform are to generate relevant data to better understand quality of life, symptoms, and medication adherence during the COVID-19 pandemic and postpandemic era; to develop a prospective real-life registry on outcomes of patients with hematologic cancer, with or without a diagnosis of COVID-19; and to facilitate patient-centered care in routine practice. METHODS: The platform consists of physician- and patient-secure portals and enables electronic patient-reported outcome (ePRO) assessments with real-time graphical presentation to physicians of individual patient symptoms and quality-of-life outcomes. Automated alerts are sent to treating hematologists based on the following predetermined criteria: presence of clinically important problems and symptoms, problems with adherence to therapy, and risk of COVID-19 diagnosis. The platform also allows physicians to set up video consultations. Clinical information regarding disease and treatment as well as clinical and survival outcomes are also prospectively collected. RESULTS: Recruitment of participants started in December 2020. As of April 2021, a total of 116 patients have been enrolled in this study. Use of this platform may help to improve patient-physician communication and help hematologists in the early recognition of clinically important problems and symptoms of their patients. More than 20 community and university-based hospitals have currently agreed to participate. In addition to patient-reported outcome data, the prospective collection of disease- and treatment-related information, as well as data on possible COVID-19 diagnosis and COVID-19 vaccination, will allow the development of a large database to also identify subgroups of patients at risk of poor outcomes. CONCLUSIONS: Data generated via this platform will help to answer clinically relevant questions for patients with hematologic malignancies during the COVID-19 pandemic and postpandemic era. The use of the GIMEMA-ALLIANCE platform in routine practice may also contribute to enhancing patient-centered care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04581187; https://clinicaltrials.gov/ct2/show/NCT04581187. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25271.

9.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266400

ABSTRACT

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Subject(s)
COVID-19 , Drug Repositioning , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Immunotherapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Comorbidity , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/immunology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompromised Host/physiology , Immunotherapy/adverse effects , Immunotherapy/methods , Immunotherapy/statistics & numerical data , Mortality , Pandemics , Prognosis , Rheumatic Diseases/epidemiology , SARS-CoV-2/physiology , Transplant Recipients/statistics & numerical data
10.
BMJ Case Rep ; 14(6)2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1266368

ABSTRACT

We describe a unique case of a patient with acute myeloid leukaemia (AML), with recurring infections during chemotherapy from chronic nasal carriage of non-diphtherial Corynebacterium, who was eventually diagnosed as she presented with neutropaenic sepsis. Identifying (often multiple) sources of infection in immunocompromised patients is crucial but deciding whether multiple organisms, which in health are considered as commensals, are actually pathogenic during vulnerable states-can be clinically difficult. Our case highlights the efforts to correctly identify the actual source of this rare organism and the recognition of its pathogenic potential when other illnesses present. We also review the literature of Corynebacteria in patients with haematological malignancies but believe this is the first case of AML to be infected with Corynebacterium presenting during the COVID-19 pandemic with a probable incidental positive swab for SARS-CoV-2.


Subject(s)
Bacteremia , COVID-19 , Bacteremia/diagnosis , Bacteremia/drug therapy , Corynebacterium , Female , Humans , Immunocompromised Host , Neoplasm Recurrence, Local , Pandemics , SARS-CoV-2
11.
J Med Virol ; 93(7): 4585-4591, 2021 07.
Article in English | MEDLINE | ID: covidwho-1263090

ABSTRACT

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, the virus has spread rapidly across the globe leading to millions of infections and subsequent deaths. Although the virus infects those exposed indiscriminately, there are groups in society at an increased risk of severe infection, leading to increased morbidity. Patients suffering from hematological cancers, particularly leukemia, lymphoma, and myeloma, may be one such group and previous studies have suggested that they may be at a three to four times greater risk of severe COVID-19 after SARS-CoV-2 infection, leading to admissions to ICU, mechanical ventilation, and death compared to those without such malignancies. Serological testing for IgG seroconversion has been extensively studied in the immunocompetent, but fewer publications have characterized this process in large series of immunocompromised patients. This study described 20 patients with hematological cancers who tested positive for SARS-CoV-2 via PCR with 12 of the patients receiving further serological testing. We found that of the 12 patients screened for SARS-CoV-2 IgG antibodies, only 2 (16.6%) were able to generate an immune response to the infection. Yet despite this low seroconversion rate in this cohort, none of these patients died or became particularly unwell with COVID-19 or its related complications.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Hematologic Neoplasms/immunology , Immunocompromised Host/immunology , SARS-CoV-2/immunology , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Testing , Disease Susceptibility/immunology , Disease Susceptibility/virology , Female , Hematologic Neoplasms/drug therapy , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Retrospective Studies , Seroconversion
12.
Clin Case Rep ; 9(6): e04013, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1263064

ABSTRACT

Patients with hematological cancer are at major risk of developing infectious complication. The prevention and treatment of COVID-19 in these patients is challenging. This experience, with the limitation of a small number of patients, highlights that early treatment of COVID-19 can overcome the infection, also in hematological patients.

13.
Br J Haematol ; 194(6): 999-1006, 2021 09.
Article in English | MEDLINE | ID: covidwho-1258906

ABSTRACT

Patients receiving targeted cancer treatments such as tyrosine kinase inhibitors (TKIs) have been classified in the clinically extremely vulnerable group to develop severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including patients with chronic myeloid leukaemia (CML) taking TKIs. In addition, concerns that immunocompromised individuals with solid and haematological malignancies may not mount an adequate immune response to a single dose of SARS-CoV-2 BNT162b2 (Pfizer-BioNTech) vaccine have been raised. In the present study, we evaluated humoral and cellular immune responses after a first injection of BNT162b2 vaccine in 16 patients with CML. Seroconversion and cellular immune response before and after vaccination were assessed. By day 21 after vaccination, anti-Spike immunoglobulin G was detected in 14/16 (87·5%) of the patients with CML and all developed a neutralising antibody response [serum dilution that inhibits 50% infection (ID50 ) >50], including medium (ID50 of 200-500) or high (ID50 of 501-2000) neutralising antibodies titres in nine of the 16 (56·25%) patients. T-cell response was seen in 14/15 (93·3%) evaluable patients, with polyfunctional responses seen in 12/15 (80%) patients (polyfunctional CD4+ response nine of 15, polyfunctional CD8+ T-cell response nine of 15). These data demonstrate the immunogenicity of a single dose of SARS-CoV-2 BNT162b2 vaccine in most patients with CML, with both neutralising antibodies and polyfunctional T-cell responses seen in contrast to patients with solid tumour or lymphoid haematological malignancies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 , Hematologic Neoplasms/immunology , Immunity, Cellular/drug effects , Immunoglobulin G/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Hematologic Neoplasms/drug therapy , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Spike Glycoprotein, Coronavirus/immunology
14.
Clin Lymphoma Myeloma Leuk ; 21(9): 606-612, 2021 09.
Article in English | MEDLINE | ID: covidwho-1252599

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) represents an important infectious complication associated with high mortality rates in patients with hematologic diseases. There have not been published any epidemiologic studies from Czech Republic so far. PATIENTS AND METHODS: This study is the first analysis of patients with hematologic malignancies and bone marrow failure syndromes treated at single hematology center in the Czech Republic between March 1 and December 31, 2020, in whom COVID-19 infection was confirmed. RESULTS: The sample comprised 96 patients aged 26 to 84 years (median, 66.0 years). At the time of their COVID-19 diagnosis, 75 patients (78.1%) were treated for hematologic diseases. Twenty-seven patients (28.1%) in the sample had complete remission (CR) of their hematologic disease. They were nonsignificantly more likely to have asymptomatic to moderate COVID-19 infection than those who failed to achieve CR (74.1% vs. 56.5%; P = .06). A more severe course of the infection was significantly correlated with older age (P = .047). Lung involvement was also statistically significantly associated with older age (P = .045). Over the study period, a total of 15 patients died. Age greater than 60 years was significantly associated with deaths from COVID-19 (P = .036), with failure to achieve CR having a statistically nonsignificant impact on mortality (P = .22). CONCLUSION: These results confirm the prognostic significance of age for achieving treatment response of hematologic disease as well as the severity and mortality of COVID-19 in hematology patients.


Subject(s)
COVID-19 , Hematologic Diseases , Adult , Aged , Aged, 80 and over , Bone Marrow Failure Disorders/complications , Bone Marrow Failure Disorders/diagnosis , Bone Marrow Failure Disorders/epidemiology , Bone Marrow Failure Disorders/therapy , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Testing/methods , COVID-19 Testing/statistics & numerical data , Czech Republic/epidemiology , Disease Progression , Female , Hematologic Diseases/complications , Hematologic Diseases/diagnosis , Hematologic Diseases/epidemiology , Hematologic Diseases/therapy , Hematologic Neoplasms/complications , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Mortality , Prevalence , SARS-CoV-2/physiology
15.
Transfusion ; 61(8): 2503-2511, 2021 08.
Article in English | MEDLINE | ID: covidwho-1243670

ABSTRACT

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation.


Subject(s)
COVID-19/complications , COVID-19/therapy , Immune Tolerance , COVID-19/immunology , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Humans , Immunization, Passive/methods , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/immunology , Organ Transplantation/adverse effects , Treatment Outcome
16.
Cancer Discov ; 11(8): 1982-1995, 2021 08.
Article in English | MEDLINE | ID: covidwho-1236486

ABSTRACT

Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T-cell responses in unexposed and SARS-CoV-2-infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4+ T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer. SIGNIFICANCE: This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.See related commentary by Salomé and Horowitz, p. 1877.This article is highlighted in the In This Issue feature, p. 1861.


Subject(s)
COVID-19 , Neoplasms , CD4-Positive T-Lymphocytes , Humans , Immunity , Programmed Cell Death 1 Receptor , SARS-CoV-2
17.
Transpl Immunol ; 67: 101412, 2021 08.
Article in English | MEDLINE | ID: covidwho-1233623

ABSTRACT

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a multisystem autoinflammatory disease due to an underlying plasma cell disorder that lacks a standard treatment strategy because of its rarity. We report a case of relapsed POEMS syndrome successfully treated with a second ambulatory autologous hematopoietic-cell transplantation (AHCT) after a daratumumab desensitization protocol performed during the coronavirus disease (COVID-19) pandemic in a patient with coexisting human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis infections. He is a 37-year old Latin-American male who had been treated with radiation, CyBorD regimen, AHCT and bortezomib therapy before being referred to our service. It was decided to administer daratumumab therapy and subsequently perform the transplant. Placement of central venous access, fluid infusion, conditioning regimen with melphalan and previously cryopreserved autograft infusion were carried out in an outpatient basis. Following second AHCT, the patient demonstrated clinical, VEGF, hematological response and remains SARS-CoV-2 infection-free and in POEMS remission with excellent quality-of-life at last follow up (6 months). We evidenced that thanks to an outpatient transplant program, the best therapeutic modalities can be offered to patients with hematologic malignancies in the context of present or future pandemics. Finally, high-complexity patients with HIV infection should have access to the same treatment strategies as non-infected patients. A second AHCT in the outpatient setting is feasible, safe and highly effective to treat patients with relapsed POEMS syndrome.


Subject(s)
HIV Infections/complications , Hematopoietic Stem Cell Transplantation , Hepatitis B, Chronic/complications , POEMS Syndrome/surgery , Syphilis/complications , Adult , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Bortezomib/therapeutic use , COVID-19/epidemiology , Humans , Immunocompromised Host , Male , SARS-CoV-2 , Transplantation, Autologous , Treatment Outcome
18.
Transplant Cell Ther ; 27(8): 697.e1-697.e5, 2021 08.
Article in English | MEDLINE | ID: covidwho-1228096

ABSTRACT

As a result of the COVID-19 pandemic, most centers performing allogeneic hematopoietic cell transplantation (allo-HCT) have switched to the use of cryopreserved grafts. Previous investigators have suggested that cryopreserved allografts may heighten risk of nonengraftment. To date, no study has investigated the effect of cryopreservation of CD34-selected hematopoietic progenitor cells (CD34+ HPCs) used as the sole graft source. In this study, we sought to evaluate outcomes after unrelated donor or matched sibling allo-HCT with cryopreserved CD34+ HPCs. This was a single-center analysis of adult patients with hematologic malignancies who underwent allo-HCT with cryopreserved CD34-selected allo-HCT grafts between January 2010 and June 2017. All patients received ablative conditioning and antirejection prophylaxis with rabbit antithymocyte globulin. G-CSF-mobilized leukapheresis products underwent CD34 selection using the CliniMACS Reagent System. Cells were then cryopreserved in DMSO (final concentration 7.5%) to -90 °C using a controlled-rate freezing system before being transferred to vapor-phase liquid nitrogen storage. In internal validation, this method has shown 92% mean CD34+ cell viability and 99.7% mean CD34+ cell recovery. Engraftment was defined as the first of 3 consecutive days of an absolute neutrophil count of ≥0.5. Platelet recovery was recorded as the first of 7 consecutive days with a platelet count ≥20 K/µL without transfusion. Kaplan-Meier methodology was used to estimate overall survival (OS) and relapse-free survival (RFS), and cumulative incidence functions were used to estimate rates of relapse, nonrelapse mortality (NRM), and acute graft-versus-host disease (GVHD). A total of 64 patients received a cryopreserved CD34-selected graft. The median CD34+ cell count before cryopreservation was 6.6 × 106/kg (range, 1.4 to 16.1 × 106/kg), and the median CD3+ cell count was 2.0 × 103/kg (range, 0 to 21.1 × 106/kg). All patients were engrafted, at a median of 11 days post-HCT (range, 8 to 14 days). One patient had poor graft function in the setting of cytomegalovirus viremia, necessitating a CD34-selected boost on day +57. The median time to platelet recovery was 16 days (range, 13 to 99 days). The estimated 2-year OS was 70% (95% confidence interval [CI], 58% to 83%) with cryopreserved grafts versus 62% (95% CI, 57% to 67%) with fresh grafts (hazard ratio [HR], 0.86; 95% CI, 0.54 to 1.35; P = .5). The estimated 2-year RFS in the 2 groups was 59% (95% CI, 48% to 74%) versus 56% (95% CI, 51% to 61%; HR, 1.01; 95% CI, 0.68 to 1.51; P > .9). The cumulative incidence of relapse at 2 years was 29% (95% CI, 17% to 41%) versus 23% (95% CI, 19% to 27%; P = .16), and the cumulative incidence of NRM at 2 years was 17% (95% CI, 9% to 28%) versus 23% (95% CI, 19% to 28%; P = .24). The cumulative incidence of grade II-IV acute GVHD by day +100 was 16% with cryopreserved grafts (95% CI, 8% to 26%) and 16% (95% CI, 13% to 20%; P = .97) with fresh grafts. Moderate to severe chronic GVHD by day +365 occurred in only 1 recipient of a cryopreserved graft (2%). Our data show that in patients with hematologic malignancies who received cryopreserved allogeneic CD34+ HPCs, engraftment, GVHD, and survival outcomes were consistent with those seen in recipients of fresh allogeneic CD34+ HPC grafts at our center. Our laboratory validation and clinical experience demonstrate the safety of our cryopreservation procedure for CD34-selected allografts.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Adult , Cryopreservation , Humans , Neoplasm Recurrence, Local , Pandemics , SARS-CoV-2
19.
BMJ Health Care Inform ; 28(1)2021 May.
Article in English | MEDLINE | ID: covidwho-1226760

ABSTRACT

OBJECTIVES: Prior research has reported an increased risk of fatality for patients with cancer, but most studies investigated the risk by comparing cancer to non-cancer patients among COVID-19 infections, where cancer might have contributed to the increased risk. This study is to understand COVID-19's imposed HR of fatality while controlling for covariates, such as age, sex, metastasis status and cancer type. METHODS: We conducted survival analyses of 4606 cancer patients with COVID-19 test results from 16 March to 11 October 2020 in UK Biobank and estimated the overall HR of fatality with and without COVID-19 infection. We also examined the HRs of 13 specific cancer types with at least 100 patients using a stratified analysis. RESULTS: COVID-19 resulted in an overall HR of 7.76 (95% CI 5.78 to 10.40, p<10-10) by following 4606 patients with cancer for 21 days after the tests. The HR varied among cancer type, with over a 10-fold increase in fatality rate (false discovery rate ≤0.02) for melanoma, haematological malignancies, uterine cancer and kidney cancer. Although COVID-19 imposed a higher risk for localised versus distant metastasis cancers, those of distant metastases yielded higher overall fatality rates due to their multiplicative effects. DISCUSSION: The results confirmed prior reports for the increased risk of fatality for patients with COVID-19 plus hematological malignancies and demonstrated similar findings of COVID-19 on melanoma, uterine, and kidney cancers. CONCLUSION: The results highlight the heightened risk that COVID-19 imposes on localised and haematological cancer patients and the necessity to vaccinate uninfected patients with cancer promptly, particularly for the cancer types most influenced by COVID-19. Results also suggest the importance of timely care for patients with localised cancer, whether they are infected by COVID-19 or not.


Subject(s)
COVID-19/mortality , Health Status , Neoplasms/mortality , Public Health Surveillance , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Neoplasms/pathology , Risk Assessment , Risk Factors , Survival Analysis , Young Adult
20.
Adv Exp Med Biol ; 1318: 657-672, 2021.
Article in English | MEDLINE | ID: covidwho-1222739

ABSTRACT

Currently, coronavirus disease 2019 (COVID-19) has spread worldwide and continues to rise. There remains a significant unmet need for patients with hematological malignancies requiring specialized procedures and treatments, like cellular therapy to treat or cure their disease. For instance, chimeric antigen receptor T (CAR-T) cell therapy is approved for relapsed/refractory (after two or more lines of therapy) diffuse large B cell lymphoma and B cell acute lymphoblastic leukemia that is refractory or in the second relapse in patients younger than 25 years of age. Similarly, hematopoietic stem cell transplantation (HSCT) can be a lifesaving procedure for many patients, such as those with acute myeloid leukemia with high-risk cytogenetics. Unfortunately, the COVID-19 pandemic has thrust upon the hematologists and transplant specialists' unique challenges with the implementation and management of cellular therapy. One of the significant concerns regarding this immunocompromised patient population is the significant risk of acquiring SARS-CoV-2 infection due to its highly contagious nature. Experts have recommended that if medically indicated, especially in high-risk disease (where chemotherapy is unlikely to work), these lifesaving procedures should not be delayed even during the COVID-19 pandemic. However, proceeding with CAR-T cell therapy and HSCT during the pandemic is a considerable task and requires dedication from the transplant team and buy-in from the patients and their family or support system. Open conversations should be held with the patients about the risks involved in undergoing cellular therapies during current times and the associated future uncertainties.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Cell- and Tissue-Based Therapy , Humans , Immunotherapy, Adoptive , Pandemics , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL