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1.
J Infect ; 88(6): 106162, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663756

ABSTRACT

OBJECTIVES: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence. METHODS: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests. RESULTS: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001). CONCLUSIONS: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.


Subject(s)
Hematopoietic Stem Cell Transplantation , Nocardia Infections , Trimethoprim, Sulfamethoxazole Drug Combination , Humans , Nocardia Infections/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Female , Case-Control Studies , Risk Factors , Middle Aged , Retrospective Studies , Adult , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Transplantation, Homologous/adverse effects , Aged , Transplant Recipients/statistics & numerical data , Nocardia/isolation & purification , Antibiotic Prophylaxis
2.
Antivir Ther ; 29(1): 13596535221097495, 2024 02.
Article in English | MEDLINE | ID: mdl-38353416

ABSTRACT

We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Cross Infection , Hematopoietic Stem Cell Transplantation , Humans , Cross Infection/drug therapy , COVID-19/diagnosis , SARS-CoV-2 , Antibodies, Neutralizing , Mutation , Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation/adverse effects
3.
Bull Cancer ; 111(2S): S78-S83, 2024 Feb.
Article in French | MEDLINE | ID: mdl-37055307

ABSTRACT

The French High Authority of Health (HAS) and National Drug Safety (ANSM) agencies recommendations issued in 2014, the French General Direction of Health (DGS) instruction published in November 2021, the French National Blood Bank (EFS) guidelines and the data available in the literature globally define "good transfusion practices" but provide little information about the immuno-hematological and transfusion management of patients who have received an allogeneic hematopoietic stem transplantation (allo-HCT). The aim of this workshop was to harmonize these practices in situations for which there are currently no recommendations. In order to anticipate possible transfusion issues after allo-HCT, we recommend performing, before the transplantation, an extended red blood cell phenotyping of the donor and a detection of HLA alloimmunization in the recipient. We recommend to systematically perform for minor ABO mismatches: a direct antiglobulin test between D8 and D20, and for major ABO mismatches; a titration of anti-A/anti-B antibodies and an erythrocyte chimerism at D100. At one-year post-transplant, we recommend carrying out an erythrocyte chimerism to allow, if necessary, the update of transfusion counselling (RH phenotype, irradiation of packed red blood cells).


Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Humans , Follow-Up Studies , Transplantation, Homologous , Erythrocyte Transfusion , Societies, Medical
4.
J Infect Dis ; 229(1): 83-94, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-37440459

ABSTRACT

BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphopenia , Metapneumovirus , Paramyxoviridae Infections , Respiratory Tract Infections , Adult , Humans , Cohort Studies , Retrospective Studies , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/etiology , Respiratory Tract Infections/drug therapy , Paramyxoviridae Infections/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adrenal Cortex Hormones/therapeutic use
5.
Transplant Cell Ther ; 30(2): 235.e1-235.e10, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38007092

ABSTRACT

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.


Subject(s)
Communicable Diseases , Hematopoietic Stem Cell Transplantation , Pneumonia, Pneumocystis , Humans , Case-Control Studies , Pneumonia, Pneumocystis/epidemiology , Pneumonia, Pneumocystis/etiology , Pneumonia, Pneumocystis/diagnosis , Bone Marrow , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Risk Factors , Communicable Diseases/etiology
6.
Transpl Infect Dis ; 25(5): e14118, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37594199

ABSTRACT

BACKGROUND: Human parvovirus B19 (B19V) infection is associated with pure red cell aplasia (PRCA) in immunocompromised patients; however, the spectrum of manifestations associated with B19V in allogeneic hematopoietic stem cell transplantation recipients (alloHSCT) has rarely been reported. METHODS: In this study, we aimed to report clinical and immune features of B19V infection after alloHSCT. We retrospectively collected and analyzed clinical and microbiological data of all transplanted patients with B19V DNAmia or tissue infection detected by polymerase chain reaction (PCR) in our center from 2010 to 2021. RESULTS: We report 35 cases of B19V infections in 33 patients. Median time from transplant to B19V first PCR positivity was 6.9 months (interquartile range (IQR) [1.6-18.9]). No preferential immune profile, type of transplantation or conditioning was identified. Hematological impairment was the most frequent sign, followed by rash and fever. Unconventional clinical forms were also detected, such as acute myelitis and myositis. For some cases, the direct relationship between symptoms and B19V infection was difficult to prove but was suggested by targeted tissue PCR positivity. When hematological impairment was not at the forefront, reticulocytopenia helped to diagnose B19V infections. Treatment was mainly based on high dose intravenous immunoglobulin. CONCLUSION: Although hematological impairment was the most frequent sign, B19V can affect multiple targets and lead to atypical manifestations. Because of its heterogeneous clinical presentation, B19V infection is likely under-diagnosed. Diagnosis of unusual B19V organ involvement needs combination of arguments which can include targeted tissue PCR.


Subject(s)
Erythema Infectiosum , Hematopoietic Stem Cell Transplantation , Parvoviridae Infections , Parvovirus B19, Human , Humans , Erythema Infectiosum/complications , Retrospective Studies , Parvovirus B19, Human/genetics , DNA, Viral/analysis , Hematopoietic Stem Cell Transplantation/adverse effects , Stem Cell Transplantation
7.
Am J Hematol ; 98(10): 1559-1570, 2023 10.
Article in English | MEDLINE | ID: mdl-37483161

ABSTRACT

Complement activation has shown a role in murine models of graft-versus-host disease (GVHD) and in endothelial complications after allogeneic hematopoietic cell transplantation (allo-HSCT). However, its impact on post-transplant outcomes has not been so far fully elucidated. Here, we conducted a prospective multicentric trial (NCT01520623) performing serial measurements of complement proteins, regulators, and CH50 activity for 12 weeks after allo-HSCT in 85 patients receiving a myeloablative conditioning (MAC) regimen for various hematological malignancies. Twenty-six out of 85 patients showed an "activated" complement profile through the classical/lectin pathway, defined as a post-transplant decline of C3/C4 and CH50 activity. Time-dependent Cox regression models demonstrated that complement activation within the first weeks after allo-HSCT was associated with increased non-relapse mortality (hazard ratio [HR]: 3.69, 95% confident interval [CI]: 1.55-8.78, p = .003) and poorer overall survival (HR: 2.72, 95% CI: 1.37-5.39, p = .004) due to increased incidence of grade II-IV acute GVHD and in particular gastrointestinal (GI) GVHD (HR: 36.8, 95% CI: 12.4-109.1, p < .001), higher incidences of thrombotic microangiopathy (HR: 8.58, 95% CI: 2.16-34.08, p = .0022), capillary leak syndrome (HR: 7.36, 95% CI: 2.51-21.66, p = .00028), post-engraftment bacterial infections (HR: 2.37, 95% CI: 1.22-4.63, p = .0108), and EBV reactivation (HR: 3.33, 95% CI: 1.31-8.45, p = .0112). Through specific immune staining, we showed the correlation of deposition of C1q, C3d, C4d, and of C5b9 components on endothelial cells in GI GVHD lesions with the histological grade of GVHD. Altogether these findings define the epidemiology and the clinical impact of complement classical/lectin pathway activation after MAC regimens and provide a rational for the use of complement inhibitory therapeutics in a post-allo-HSCT setting.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Animals , Mice , Endothelial Cells/pathology , Prospective Studies , Neoplasm Recurrence, Local , Hematopoietic Stem Cell Transplantation/adverse effects , Complement Activation , Transplantation Conditioning/adverse effects , Retrospective Studies
8.
iScience ; 26(5): 106763, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37168557

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients show lower humoral vaccine responsiveness than immunocompetent individuals. HLA diversity, measured by the HLA evolutionary divergence (HED) metrics, reflects the diversity of the antigenic repertoire presented to T cells, and has been shown to predict response to cancer immunotherapy. We retrospectively investigated the association of HED with humoral response to SARS-CoV-2 vaccine in allo-HSCT recipients. HED was calculated as pairwise genetic distance between alleles at HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci in recipients and their donors. Low anti-spike IgG levels (<30 BAU/mL) were associated with short time from allo-SCT and low donor DPB1-HED, mostly related to donor DPB1 homozygosity. The diversity of donor HLA-DP molecules, assessed by heterozygosity or sequence divergence, may thus impact the efficacy of donor-derived CD4 T cells to sustain vaccine-mediated antibody response in allo-HSCT recipients.

9.
Front Immunol ; 14: 1125824, 2023.
Article in English | MEDLINE | ID: mdl-36960069

ABSTRACT

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.


Subject(s)
COVID-19 , Communicable Diseases , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Humans , Middle Aged , Bone Marrow , Transplantation, Homologous , COVID-19/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Communicable Diseases/complications , Cytomegalovirus Infections/complications , Registries
10.
J Autoimmun ; 136: 103024, 2023 04.
Article in English | MEDLINE | ID: mdl-37001437

ABSTRACT

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.


Subject(s)
Autoimmune Diseases , COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , SARS-CoV-2 , RNA, Viral , Transplant Recipients , Hematopoietic Stem Cell Transplantation/adverse effects , Autoimmune Diseases/epidemiology , Autoimmune Diseases/therapy
11.
Med Mycol ; 61(4)2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36963767

ABSTRACT

To describe reasons for initiation and evolution under isavuconazole (ISZ), a 2-year prospective and observational study was performed. Anonymized data collected during the first 3 months of treatment were indications of treatment, efficacy, overall survival (OS), evolution of toxicity markers, and ISZ trough levels. Fifty-one (26 invasive aspergillosis, 16 prophylaxis, and 9 mucormycosis) patients started on isavuconazole. Isavuconazole was initiated upfront in 12/51 cases, especially to avoid toxicities from other antifungals. As second-line therapy (39/51 patients), isavuconazole was mostly initiated after toxicities of the previous treatments (66.7%; 26/39 cases). An improvement in toxicity markers was reported in most patients. However, five patients experienced adverse events. The mean ISZ trough levels measured from 179 samples collected in 37 patients was 3.33 ± 1.64 mg/l. The mean ISZ through levels was significantly lower (P = .003) in alloHSCT recipients (3.10 ± 1.45 mg/l) than in other patients (3.76 ± 1.88 mg/l) but still within the expected range of efficacy. After 12 weeks, the OS was 69.2% (n = 18/26) in the invasive aspergillosis intention-to-treat (ITT) group and 44.4% (n = 4/9) in the mucormycosis ITT group. After 2 years, the OS was respectively 46.2% (n = 12/26) and 33.3% (n = 3/9) in these two groups.


Isavuconazole is commonly prescribed as second-line therapy after the toxicity of a previous treatment. In most cases, an improvement is reported. The well tolerability of isavuconazole was associated with correct blood levels, even in alloHSCT recipients.


Subject(s)
Aspergillosis , Invasive Fungal Infections , Mucormycosis , Animals , Mucormycosis/drug therapy , Mucormycosis/veterinary , Prospective Studies , Triazoles/adverse effects , Antifungal Agents/adverse effects , Aspergillosis/drug therapy , Aspergillosis/veterinary , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/veterinary
12.
Br J Haematol ; 201(6): 1066-1071, 2023 06.
Article in English | MEDLINE | ID: mdl-36921963

ABSTRACT

This 16-month-long multicentre retrospective study of 225 allogeneic haematopoietic stem cell transplantation (alloHSCT) recipients with COVID-19 examines risk factors for severity and mortality, describing the successive waves of infections (from March to June 2020 and from August 2020 to June 2021). We confirm the negative role of low respiratory tract disease and immunosuppressive treatment. We highlight significantly lower percentages of severe forms and COVID-19-related mortality during the second wave. Monthly comparative evolution of cases in alloHSCT recipients and in the French population shows a higher number of cases in alloHSCT recipients during the first wave and a decrease from February 2021.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , COVID-19/etiology , Immunosuppressive Agents/adverse effects , Risk Factors
13.
Haematologica ; 108(9): 2369-2379, 2023 09 01.
Article in English | MEDLINE | ID: mdl-36951151

ABSTRACT

Debates on the role and timing of allogeneic hemtopoietic stem cell transplantation (HSCT) in acute myelogenous leukemia (AML) have persisted for decades. Time to transplant introduces an immortal time and current treatment algorithm mainly relies on the European LeukemiaNet disease risk classification. Previous studies are also limited to age groups, remission status and other ill-defined parameters. We studied all patients at diagnosis irrespective of age and comorbidities to estimate the cumulative incidence and potential benefit or disadvantage of HSCT in a single center. As a time-dependent covariate, HSCT improved overall survival in intermediate- and poor-risk patients (hazard ratio =0.51; P=0.004). In goodrisk patients only eight were transplanted in first complete remission. Overall, the 4-year cumulative incidence of HSCT was only 21.9% but was higher (52.1%) for patients in the first age quartile (16-57 years old) and 26.4% in older patients (57-70 years old) (P<0.001). It was negligible in patients older than 70 years reflecting our own transplant policy but also barriers to transplantation (comorbidities and remission status). However, HSCT patients need to survive, be considered eligible both by the referring and the HSCT physicians and have a suitable donor to get transplantation. We, thus, comprehensively analyzed the complete decision-making and outcome of all our AML patients from diagnosis to last followup to decipher how patient allocation and therapy inform the value of HSCT. The role of HSCT in AML is shifting with broad access to different donors including haploidentical ones. Thus, it may (or may not) lead to increased numbers of allogeneic HSCT in AML in adults.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Humans , Aged , Adolescent , Young Adult , Middle Aged , Transplantation, Homologous , Leukemia, Myeloid, Acute/therapy , Remission Induction , Proportional Hazards Models , Retrospective Studies
16.
Bone Marrow Transplant ; 58(2): 152-159, 2023 02.
Article in English | MEDLINE | ID: mdl-36335254

ABSTRACT

Weekly blood Toxoplasma gondii DNA screening using real-time quantitative polymerase chain reaction (qPCR) has been implemented in all allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients at our hospital. We retrospectively analyzed the consequences of a positive blood qPCR in the management of Toxoplasma infection (TI) and disease (TD).From 2011 to 2020, 52 (4.13%) of 1 257 alloHSCT recipients had at least one positive qPCR, 45 (3.5%) with TI and seven (0.56%) with TD (central nervous system involvement). Forty-four patients were qPCR-positive before day 100, 30 without and 14 with anti-Toxoplasma prophylaxis. Twenty-five of them (56.8%) started or continued prophylactic dosage treatment: all became qPCR-negative, including 20 (80%) receiving only prophylactic dosage treatment. Twenty-four of them (54.5%) received non-prophylactic dosage treatment: qPCR became negative in 22/24 (91.7%), while TI contributed to death in two cases. Six of the eight patients diagnosed after D100 had breakthrough TI or TD. No death was attributable to TI or TD. qPCR kinetics available for 24 patients increased until anti-Toxoplasma treatment began, then decreased with all treatment regimens.Clinical follow-up and qPCR monitoring with quantification of the parasitic load appears a reasonable strategy to avoid TD and to use minimal effective dosage of anti-Toxoplasma treatments.


Subject(s)
Hematopoietic Stem Cell Transplantation , Toxoplasma , Toxoplasmosis , Humans , Toxoplasma/genetics , Toxoplasmosis/diagnosis , Retrospective Studies , Real-Time Polymerase Chain Reaction
17.
Vaccine ; 40(33): 4682-4685, 2022 08 05.
Article in English | MEDLINE | ID: mdl-35840470

ABSTRACT

Previous studies reporting the response to SARS-CoV-2 mRNA vaccination in alloHSCT recipients used serological and/or cellular assays, but no study has evaluated vaccine-induced neutralizing antibodies. We prospectively studied 28 alloHSCT recipients who received two BNT162b2 doses. Two patients groups were defined according to time from alloHSCT and immunosuppressive treatment, and had different baseline immunologic status. Study end-point was the evaluation of humoral and cellular responses one month after the second vaccine. All patients seroconverted. Anti-S IgG levels and neutralizing antibodies percentages were not significantly different between both groups. Using IFNγ ELISpot assay, five patients showed a strong increase, without correlation with the humoral response. Using flow cytometry lymphocyte proliferation assay, 14 patients exhibited responding T cells, without difference between both groups or correlation with anti-S IgG levels. A few low serological responders had a detectable CD4 + T cell proliferative response. This finding should be confirmed in a larger cohort.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Immunity, Humoral , Immunoglobulin G , SARS-CoV-2 , Vaccination
18.
Bone Marrow Transplant ; 57(9): 1365-1372, 2022 09.
Article in English | MEDLINE | ID: mdl-35654824

ABSTRACT

Reduced intensity conditionings (RIC) before after allogeneic hematopoietic stem cell transplantation (HSCT) allow older or unfit patients of being transplanted, but survival expectancy and burden of late complications are poorly described in this setting. All patients (N = 456) who were alive and relapse-free 2 years after HSCT following RIC were included. Cumulative incidences (CI), standardized incidence, or mortality, ratio (SIR or SMR), and competing risk models were used. The 10-year CIs of relapse and non-relapse mortality incidences were 13.9 and 13.4%, respectively. Seventy-eight patients died, late relapse being the most frequent cause of death leading to a SMR of 6.38 (95% CI, 5.1-8.0; p < 0.001). Among non-relapsing patients (n = 412), 30 died (SMR 4.38; 95% CI, 3.3-5.8: p < 0.001). A total of 37 patients developed 41 SM leading to a 10-year cumulative incidence of 12.9%, and a significant SIR relative to the general population (1.4). Finally, we found high CI of cardiovascular (CVC) and venous thromboembolic complications (VTE) (10-year CI; 15.1% and 11.7%, respectively). Older age was the only significant risk factor for CVC and VTE in multivariable analysis. In conclusion, with life expectancy rate of 70%, late survivors after RIC warrants long-term follow-up and active intervention on averting cardiovascular disease and screening cancers.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Venous Thromboembolism , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Life Expectancy , Recurrence , Retrospective Studies , Transplantation Conditioning/adverse effects , Transplantation, Homologous/adverse effects , Venous Thromboembolism/complications
19.
Blood Adv ; 6(16): 4763-4772, 2022 08 23.
Article in English | MEDLINE | ID: mdl-35667096

ABSTRACT

Acute graft-versus-host disease (GVHD) is still the major contributor to comorbidities and mortality after allogeneic hematopoietic stem cell transplantation. The use of plasmatic biomarkers to predict early outcomes has been advocated in the past decade. The purpose of this prospective noninterventional study was to test the ability of panels including 7 biomarkers (Elafin, HGF, IL2RA, IL8, REG3, ST2, and TNFRI), to predict day 28 (D28) complete response to steroid, D180 overall survival, and D180 nonrelapse mortality (NRM). Using previous algorithms developed by the Ann Arbor/MAGIC consortium, 204 patients with acute GVHD were prospectively included and biomarkers were measured at GVHD onset for all of them. Initial GVHD grade and bilirubin level were significantly associated with all those outcomes. After adjustment on clinical variables, biomarkers were associated with survival and NRM. In addition to clinical variables, biomarkers slightly improved the prediction of overall survival and NRM (concordance and net reclassification indexes). The potential benefit of adding biomarkers panel to clinical parameters was also investigated by decision curve analyses. The benefit of adding biomarkers to clinical parameters was however marginal for the D28 nonresponse and mortality endpoints.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Algorithms , Biomarkers , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Prospective Studies
20.
Bone Marrow Transplant ; 57(8): 1287-1294, 2022 08.
Article in English | MEDLINE | ID: mdl-35596063

ABSTRACT

BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (allo-HCT). Recent evaluation of BKPyV HC (BKHC) incidence and risk factors are scarce. We conducted a retrospective single-center study on a recent allo-HCT cohort over 3 years in a referral academic hospital for hematological malignancies. Primary objective was to determine BKHC incidence using competitive risk analysis. Secondary objectives were the identification of HC risk factors using Fine and Gray models and the evaluation of mortality. Among 409 allo-HCT recipients (median age 47 years), 41 developed BKHC after a median delay of 41 [32-55] days. Incidence density of BKHC was 2.4 [1.8-3.1] events per 100 days post-allo-HCT. The proportion of BKHC after adjustment for time-dependent competing risk was 9.5 [9.5-9.6]% at 100 days. BK viremia was detected in 63 versus 20% in tested patients with and without BKHC, respectively. After adjustment for confounders, myeloablative conditioning regimen with and without cyclophosphamide and CMV seropositivity were independently associated with BKHC. Post-transplantation cyclophosphamide was not associated with BKHC. BKHC resolved in 90% of the patients. No difference in mortality was found between patients with or without BKHC. In parallel to the recent evolution of allo-HCT protocols, BKHC remains a frequent complication following allo-HCT.


Subject(s)
BK Virus , Cystitis , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Polyomavirus Infections , Cyclophosphamide , Cystitis/epidemiology , Cystitis/etiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Incidence , Middle Aged , Polyomavirus Infections/epidemiology , Polyomavirus Infections/etiology , Retrospective Studies , Risk Factors
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