scholarly journals The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

2022 ◽  
Vol 12 ◽  
Author(s):  
Karyl S. Barron ◽  
Ivona Aksentijevich ◽  
Natalie T. Deuitch ◽  
Deborah L. Stone ◽  
Patrycja Hoffmann ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Inadequate Response ◽  
Cell Transplant ◽  
Inherited Disease ◽  
Single Center ◽  
Livedo Racemosa ◽  
Cutaneous Manifestations ◽  
Adenosine Deaminase 2

The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease that has undergone extensive phenotypic expansion since being first described in patients with fevers, recurrent strokes, livedo racemosa, and polyarteritis nodosa in 2014. It is now recognized that patients may develop multisystem disease that spans multiple medical subspecialties. Here, we describe the findings from a large single center longitudinal cohort of 60 patients, the broad phenotypic presentation, as well as highlight the cohort’s experience with hematopoietic cell transplantation and COVID-19. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory, and hematologic, however, most patients presented with significant overlap between these three phenotype groups. The cardinal features of the inflammatory/vascular group included cutaneous manifestations and stroke. Evidence of immune dysregulation was commonly observed, including hypogammaglobulinemia, absent to low class-switched memory B cells, and inadequate response to vaccination. Despite these findings, infectious complications were exceedingly rare in this cohort. Hematologic findings including pure red cell aplasia (PRCA), immune-mediated neutropenia, and pancytopenia were observed in half of patients. We significantly extended our experience using anti-TNF agents, with no strokes observed in 2026 patient months on TNF inhibitors. Meanwhile, hematologic and immune features had a more varied response to anti-TNF therapy. Six patients received a total of 10 allogeneic hematopoietic cell transplant (HCT) procedures, with secondary graft failure necessitating repeat HCTs in three patients, as well as unplanned donor cell infusions to avoid graft rejection. All transplanted patients had been on anti-TNF agents prior to HCT and received varying degrees of reduced-intensity or non-myeloablative conditioning. All transplanted patients are still alive and have discontinued anti-TNF therapy. The long-term follow up afforded by this large single-center study underscores the clinical heterogeneity of DADA2 and the potential for phenotypes to evolve in any individual patient.

scholarly journals Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients

2021 ◽  
Author(s):  
Hasan Hashem ◽  
Giorgia Bucciol ◽  
Seza Ozen ◽  
Sule Unal ◽  
Ikbal Ok Bozkaya ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Failure ◽  
Hematopoietic Cell ◽  
Recurrent Fever ◽  
Vascular Events ◽  
Livedo Racemosa ◽  
Conditioning Regimens ◽  
Adenosine Deaminase 2

Abstract Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2–28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5–16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.

scholarly journals Management of Herpesvirus Infections in Hematopoietic Cell Transplant Recipients

2021 ◽  
Vol 2 (1) ◽  
pp. 8-21
Author(s):  
Jan Styczynski
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cellular Therapy ◽  
Hematopoietic Cell ◽  
Host Cells ◽  
Preventive Strategy ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Screening Assay ◽  
Specific Level

Following primary infection, herpesviruses establish latency in infected individuals in the host cells and may reactivate upon external stimuli and during periods of immunosuppression. The objective of this paper was to the present current strategies on preventive and therapeutic management of infections with herpesviruses in recipients of hematopoietic cell transplantation. Strategies of antiviral management include prophylaxis, pre-emptive treatment and targeted treatment. Empirical therapy is not used in antiviral strategies. Prophylaxis can be done at universal (preventive strategy) and specific level. Universal prophylaxis includes non-pharmacologic methods of prevention of infection or reactivation. Risk-adapted specific prophylaxis includes use of specific antivirals or cellular therapy or other specific methods in order to prevent specific infection, in high-risk groups. Pre-emptive therapy means use of therapeutic approaches in asymptomatic infection, detected by a screening assay. Targeted therapy is used in established specific viral end-organ infections. The following sections of the paper refer to prophylaxis and treatment strategies, respectively, against CMV, EBV, HSV, VZV, HHV-6, HHV-7, and HHV-8 after allogeneic hematopoietic cell transplantation.

scholarly journals Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience

2018 ◽  
Vol 18 (1) ◽  
pp. e35-e39 ◽  
Author(s):  
Mohamed A. Kharfan-Dabaja ◽  
Ambuj Kumar ◽  
Facundo E. Stingo ◽  
Farhad Khimani ◽  
Mohammad Hussaini ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Single Center ◽  
Single Center Experience ◽  
Richter Syndrome

scholarly journals The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for nonmalignant diseases

Blood ◽  
2019 ◽  
Vol 133 (7) ◽  
pp. 754-762 ◽  
Author(s):  
Monica S. Thakar ◽  
Larisa Broglie ◽  
Brent Logan ◽  
Andrew Artz ◽  
Nancy Bunin ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Cox Regression ◽  
Bone Marrow Failure ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Research Database ◽  
Hematopoietic Cell Transplant ◽  
Risk Of Death ◽  
Increased Risk ◽  
Comorbidity Index

Abstract Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.

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