Late Effects Screening Guidelines after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement From the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects After Pediatric HCT

Dietz, Andrew C.; Savage, Sharon A.; Vlachos, Adrianna; Mehta, Parinda A.; Bresters, Dorine; Tolar, Jakub; Bonfim, Carmem; Dalle, Jean Hugues; Fuente, Josu de la; Skinner, Roderick; Boulad, Farid; Duncan, Christine; Baker, K. Scott; Pulsipher, Michael A.; Lipton, Jeffrey M.; Wagner, John E.; Alter, Blanche P.

doi:10.1016/j.bbmt.2017.05.022

Cited by 47 publications

(30 citation statements)

References 69 publications

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“…DC and FA are associated with high transplant regimen-related toxicities and require modified transplant conditioning regimens. [20][21][22] Of note, chromosomal breakage may be elevated at baseline in patients who have received prior chemotherapy, but increased breakage with diepoxybutane and mitomycin C is a classic feature of FA. Similar patterns of chromosomal breakage are seen in Nijmegen breakage syndrome.…”

Section: Initial Evaluationmentioning

confidence: 99%

Genetic predisposition to MDS: diagnosis and management

Furutani

Shimamura

2019

Hematology

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Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by clonal hematopoiesis with a propensity to evolve into acute myeloid leukemia. MDS presenting in children and young adults is associated with features clinically and biologically distinct from MDS arising in older adults. MDS presenting in children and young adults is associated with a higher likelihood of an underlying genetic predisposition; however, genetic predisposition is increasingly recognized in a subset of older adults. The diagnosis of a genetic predisposition to MDS informs clinical care and treatment selection. Early diagnosis allows a tailored approach to management and surveillance. Genetic testing now offers a powerful diagnostic approach but also poses new challenges and caveats. Clinical expertise in these disorders together with scientific expertise regarding the affected genes is essential for diagnosis. Understanding the basic mechanisms of genetic predisposition to myeloid malignancies may inform surveillance strategies and lead to novel therapies. The cases presented in this article illustrate challenges to the diagnosis of germline genetic predisposition to MDS and how the diagnosis affects clinical management and treatment.

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Section: Initial Evaluationmentioning

confidence: 99%

Genetic predisposition to MDS: diagnosis and management

Furutani

Shimamura

2019

Hematology

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“…In addition, most relevant chronic toxicities include fertility issues and the risk for secondary malignancies, which may be of even greater relevance in DBA given that it is a cancer predisposition syndrome (Dietz et al , ). Guidelines for the long‐term follow‐up of marrow failure patients after HSCT have recently been updated (Dietz et al , ). Counselling for techniques aiming to preserve fertility prior to transplant is indicated, including ovarian preservation and/or oocyte or sperm cryopreservation (Bastings et al , ; Jensen et al , ; Stukenborg et al , ) irrespective of age and sex, and is currently offered to all HSCT patient in our centre before starting chemotherapy.…”

Section: Treatmentmentioning

confidence: 99%

How I manage children with Diamond‐Blackfan anaemia

Bartels

Bierings

2018

Br J Haematol

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Summary Diamond‐Blackfan anaemia ( DBA ) is a rare inherited marrow failure disorder, characterized by hypoplastic anaemia, congenital anomalies and a predisposition to cancer as a result of ribosomal dysfunction. Historically, treatment is based on glucocorticoids and/or blood transfusions, which is accompanied by significant toxicity and long‐term sequelae. Currently, stem cell transplantation is the only curative option for the haematological DBA phenotype. Whereas this procedure has been quite successful in the last decade in selected patients, novel therapies and biological insights are still warranted to improve clinical care for all DBA patients. In addition to paediatric haematologists, other physicians (e.g. endocrinologist, gynaecologist) should ideally be involved in the care of this chronic condition from an early age, to improve lifelong management of haematological and non‐haematological symptoms, and screen for DBA ‐associated malignancies. Here we provide an overview of current knowledge and recommendations for the day‐to‐day care of DBA patients.

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“…The HCT-specific regimen for each patient must be tailored based on the patient's disorder, underlying comorbidities, and consideration of late HCT effects, particularly for those syndromes (eg, DC) in which transplantation will improve hematopoiesis but will not improve other significant symptoms (eg, pulmonary fibrosis) and may increase cancer risk later in life. 47 Selection of related HCT donors must take the underlying genetics into account. Given the variable penetrance, delayed presentation and subtle findings in most of these syndromes affected family members can be missed without genetic and/or proper diagnostic evaluations.…”

Section: Treatment Of Mds or Leukemia In Patients With Genetic Predismentioning

confidence: 99%

Pediatric leukemia susceptibility disorders: manifestations and management

McReynolds

Savage

2017

Hematology

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The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.

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Late Effects Screening Guidelines after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement From the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects After Pediatric HCT

Cited by 47 publications

References 69 publications

Genetic predisposition to MDS: diagnosis and management

Genetic predisposition to MDS: diagnosis and management

How I manage children with Diamond‐Blackfan anaemia

Pediatric leukemia susceptibility disorders: manifestations and management

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