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2.
Int J Mol Sci ; 23(15)2022 Aug 06.
Article in English | MEDLINE | ID: covidwho-1994086

ABSTRACT

Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) and mismatched haploidentical HSCT adult recipients. However, there are no published data in pediatric patients with acute myeloid leukemia who received matched-donor HSCT with PTCy. We demonstrate, in this case series, that the use of PTCy in this population is potentially safe, effective in preventing acute GVHD, does not impair engraftment, is associated with reduced non-relapse mortality, and does not hinder immune reconstitution post HSCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Child , Cyclophosphamide/therapeutic use , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Humans , Leukemia, Myeloid, Acute/drug therapy , Recurrence , Retrospective Studies , Siblings , Unrelated Donors
3.
Blood Rev ; 56: 100984, 2022 11.
Article in English | MEDLINE | ID: covidwho-1885637

ABSTRACT

Individuals with hematological malignancies and hematopoietic stem cell transplant (HCT) recipients are immunologically heterogenous groups with varying degrees of immunosuppression at increased risk of severe disease and mortality from SARS-CoV-2 infection. SARS-CoV-2 vaccines are key interventions to preventing severe COVID-19 and its complications. While these individuals were excluded from initial vaccine trials, there is now a growing body of acceptable safety and immunogenicity data among these individuals. A consistent signal for new or worsening graft versus host disease in allogeneic HCT recipients has not been demonstrated post-vaccination. Immunogenicity in these populations is variable depending on disease and treatment factors. However, serological responses may not accurately reflect vaccine protection as correlates of protection within these populations are not yet established. Large-scale studies powered to identify rare serious events, resolve differences in vaccine responses between different vaccination strategies, and identify immune correlates of protection within these populations are needed.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematologic Neoplasms , Humans , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control
5.
Front Immunol ; 13: 839844, 2022.
Article in English | MEDLINE | ID: covidwho-1775672

ABSTRACT

Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from in vitro studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Animals , COVID-19/therapy , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/etiology , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Pregnancy , SARS-CoV-2
9.
Transpl Immunol ; 68: 101435, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294281

ABSTRACT

Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to "isolation ward" due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.


Subject(s)
Antifungal Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Carcinoma, Hepatocellular/therapy , Cytomegalovirus Infections , Cytomegalovirus , Graft vs Host Disease/drug therapy , Liver Neoplasms/therapy , Liver Transplantation , SARS-CoV-2 , Acute Disease , Cytomegalovirus Infections/drug therapy , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/virology , Humans , Male , Middle Aged
10.
J Pediatr Hematol Oncol ; 44(2): e474-e478, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1232240

ABSTRACT

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.


Subject(s)
COVID-19/complications , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Myelodysplastic Syndromes/therapy , Pneumonia, Viral/pathology , Pulmonary Aspergillosis/pathology , Pulmonary Emphysema/pathology , Adolescent , COVID-19/virology , Female , Graft vs Host Disease/etiology , Humans , Myelodysplastic Syndromes/pathology , Pneumonia, Viral/etiology , Prognosis , Pulmonary Aspergillosis/etiology , Pulmonary Emphysema/etiology , Risk Factors , SARS-CoV-2/isolation & purification
11.
Blood Adv ; 5(3): 861-871, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1072926

ABSTRACT

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019 as the causative agent of COVID-19, was declared a pandemic by the World Health Organization on 11 March 2020. Widespread community transmission in the United States triggered a nationwide shutdown, raising major challenges for administration of hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor (CAR)-T cell therapies, leading many centers to delay or cancel operations. We sought to assess the impact of the COVID-19 pandemic on operations and clinical outcomes for HSCT and CAR-T cellular therapies at the Dana-Farber Cancer Institute by reviewing administration and outcomes in 127 cell therapy patients treated during the initial COVID-19 surge: 62 adult allogeneic HSCT (allo-HSCT), 38 autologous HSCT (auto-HSCT), and 27 CAR-T patients. Outcomes were compared with 66 allo-HSCT, 43 auto-HSCT, and 33 CAR-T patients treated prior to the pandemic. A second control cohort was evaluated for HSCT groups to reflect seasonal variation in infections. Although there were changes in donor selection and screening as well as cryopreservation patterns of donor products, no differences were observed across groups in 100-day overall survival, progression-free survival, rates of non-COVID-19 infections, including hospital length of stay, neutrophil engraftment, graft failure, acute graft-versus-host disease in allo-HSCT patients, or cytokine release syndrome and neurotoxicity in CAR-T patients. No HSCT patients contracted COVID-19 between days 0 and 100. One CAR-T patient contracted COVID-19 at day +51 and died of the disease. Altogether, our data indicate that cellular therapies can be safely administered throughout the ongoing COVID-19 pandemic with appropriate safeguards.


Subject(s)
COVID-19/therapy , Hematopoietic Stem Cell Transplantation , Adult , Aged , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunotherapy, Adoptive , Kaplan-Meier Estimate , Male , Middle Aged , Progression-Free Survival , SARS-CoV-2/isolation & purification , Transplantation, Autologous , Transplantation, Homologous , United States , Young Adult
13.
Br J Haematol ; 193(1): 43-51, 2021 04.
Article in English | MEDLINE | ID: covidwho-1066629
14.
Lab Invest ; 101(3): 274-279, 2021 03.
Article in English | MEDLINE | ID: covidwho-968368

ABSTRACT

Disorders involving injury to tissue stem cells that ensure normal tissue homeostasis and repair have potential to show unusually devastating clinical consequences. Acute graft-versus-host disease (aGVHD) is one condition where relatively few cytotoxic immune cells target skin stem cells to produce significant morbidity and mortality. By analogy, SARS-CoV-2 is a vector that initially homes to pulmonary stem cells that preferentially express the ACE2 receptor, thus potentially incurring similarly robust pathological consequences. In older individuals, stem cell number and/or function become depleted due to pathways independent of disease-related injury to these subpopulations. Accordingly, pathologic targeting of stem cells in conditions like aGVHD and COVID-19 infection where these cells are already deficient due to the aging process may have dire consequences in elderly individuals. A hypothesis is herein advanced that, as with aGVHD, lung stem cell targeting is a potential co-factor in explaining age-related severity of COVID-19 infection.


Subject(s)
COVID-19/etiology , Graft vs Host Disease/etiology , SARS-CoV-2 , Age Factors , Aging/immunology , Aging/pathology , COVID-19/immunology , COVID-19/pathology , Graft vs Host Disease/immunology , Graft vs Host Disease/pathology , Humans , Lung/immunology , Lung/pathology , Models, Biological , Risk Factors , SARS-CoV-2/pathogenicity , Skin/immunology , Skin/pathology , Stem Cells/immunology , Stem Cells/pathology
15.
J Transl Med ; 18(1): 451, 2020 11 30.
Article in English | MEDLINE | ID: covidwho-949113

ABSTRACT

BACKGROUND: During the coronavirus disease-2019 (COVID-19) pandemic, Italian hospitals faced the most daunting challenges of their recent history, and only essential therapeutic interventions were feasible. From March to April 2020, the Laboratory of Advanced Cellular Therapies (Vicenza, Italy) received requests to treat a patient with severe COVID-19 and a patient with acute graft-versus-host disease with umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Access to clinics was restricted due to the risk of contagion. Transport of UC-MSCs in liquid nitrogen was unmanageable, leaving shipment in dry ice as the only option. METHODS: We assessed effects of the transition from liquid nitrogen to dry ice on cell viability; apoptosis; phenotype; proliferation; immunomodulation; and clonogenesis; and validated dry ice-based transport of UC-MSCs to clinics. RESULTS: Our results showed no differences in cell functionality related to the two storage conditions, and demonstrated the preservation of immunomodulatory and clonogenic potentials in dry ice. UC-MSCs were successfully delivered to points-of-care, enabling favourable clinical outcomes. CONCLUSIONS: This experience underscores the flexibility of a public cell factory in its adaptation of the logistics of an advanced therapy medicinal product during a public health crisis. Alternative supply chains should be evaluated for other cell products to guarantee delivery during catastrophes.


Subject(s)
COVID-19/therapy , Delivery of Health Care/organization & administration , Dry Ice , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Point-of-Care Systems/organization & administration , Transportation , Acute Disease , COVID-19/epidemiology , COVID-19/pathology , Cell Proliferation , Cell Survival , Cells, Cultured , Cord Blood Stem Cell Transplantation/adverse effects , Delivery of Health Care/standards , Equipment and Supplies, Hospital/standards , Equipment and Supplies, Hospital/supply & distribution , Graft vs Host Disease/etiology , Graft vs Host Disease/pathology , Graft vs Host Disease/therapy , Humans , Italy/epidemiology , Materials Management, Hospital/organization & administration , Materials Management, Hospital/standards , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/standards , Mesenchymal Stem Cells/physiology , Organization and Administration/standards , Pandemics , Phenotype , Point-of-Care Systems/standards , SARS-CoV-2/physiology , Severity of Illness Index , Transportation/methods , Transportation/standards
17.
Clin Lymphoma Myeloma Leuk ; 20(11): 720-723, 2020 11.
Article in English | MEDLINE | ID: covidwho-614242

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has a high death rate in patients with comorbidities or in an immunocompromised state. We report a mild and attenuated SARS CoV-2 infection in a patient who is 17 months post stem cell transplantation and maintained on the JAK/STAT inhibitor ruxolitinib, a proposed novel therapy for SARS CoV-2 pneumonia.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Pneumonia, Viral/diagnosis , Pyrazoles/therapeutic use , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Humans , Immunocompromised Host , Lymphoma, T-Cell/immunology , Lymphoma, T-Cell/therapy , Male , Middle Aged , Nitriles , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pyrimidines , SARS-CoV-2 , Severity of Illness Index , Transplantation, Homologous/adverse effects , Treatment Outcome
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