Congenital Bone Marrow Failure Syndromes

Inherited syndromes characterized by deficiency or absence of various blood cells due to mutations that affect HEMATOPOIETIC STEM CELLS development and proliferation.

Also Known As:

BMF Syndrome, Inherited; Bone Marrow Failure Syndromes, Congenital; Bone Marrow Failure Syndromes, Inherited; CBMFS; Congenital Bone Marrow Failure Syndrome; IBMFS; Inherited BMF Syndrome; Inherited BMF Syndromes; Inherited Bone Marrow Failure Syndrome; Inherited Bone Marrow Failure Syndromes

Networked: 115 relevant articles (12 outcomes, 7 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Congenital Bone Marrow Failure Syndromes
2.	Dyskeratosis Congenita (X-Linked Dyskeratosis Congenita)
3.	Fanconi Anemia (Fanconi's Anemia)
4.	Diamond-Blackfan Anemia (Anemia, Diamond Blackfan)
5.	Neoplasms (Cancer)

Experts

1.	Alter, Blanche P: 18 articles (01/2022 - 09/2007)
2.	Savage, Sharon A: 16 articles (12/2023 - 09/2007)
3.	Giri, Neelam: 13 articles (01/2022 - 09/2007)
4.	Vlachos, Adrianna: 5 articles (12/2017 - 11/2010)
5.	Dror, Yigal: 4 articles (04/2022 - 08/2007)
6.	Calado, Rodrigo T: 4 articles (01/2022 - 08/2007)
7.	Lipton, Jeffrey M: 4 articles (09/2017 - 01/2014)
8.	Ellis, Steven R: 4 articles (01/2017 - 01/2014)
9.	Lansdorp, Peter M: 4 articles (02/2008 - 06/2007)
10.	Wagner, John E: 3 articles (03/2024 - 05/2017)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Congenital Bone Marrow Failure Syndromes:

1.	fludarabineIBA 10/01/2023 - "These data highlight how HSCT using low-dose Cy as part of a fludarabine-based regimen is safe and effective in SAA/non-Fanconi anaemia IBMFS." 10/01/2023 - "The paper by Alsultan et al. report the safety and efficacy of MRD HSCT conditioned with low-dose cyclophosphamide, fludarabine and thymoglobulin in both aSAA and non-Fanconi iBMFs, strengthening the concept of the pivotal role of immunosuppressive approach in allo-HSCT for specific subgroups of non-malignant diseases requiring a reduced risk of toxicities, offering the opportunity to discuss the essential points for achieving patients' long-term survival after MRD HSCT in BMF. " 03/01/2024 - "This issue of Progress in Hematology covers four topics related to aplastic anemia: (1) laboratory markers to identify immune pathophysiology and their role on differential diagnosis and prognosis, (2) the path to combination therapy with horse anti-thymocyte globulin, cyclosporine A, and eltrombopag, (3) more than 60 years of history and recent trends in allogeneic HSCT, and (4) genetic testing for differential diagnosis from IBMFS and novel approaches to transplantation for children including fludarabine/melphalan-based conditioning." 01/01/2022 - "Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophos-phamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. "
2.	Cyclophosphamide (Cytoxan)FDA LinkGeneric 01/01/2024 - "5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. " 10/01/2023 - "The paper by Alsultan et al. report the safety and efficacy of MRD HSCT conditioned with low-dose cyclophosphamide, fludarabine and thymoglobulin in both aSAA and non-Fanconi iBMFs, strengthening the concept of the pivotal role of immunosuppressive approach in allo-HSCT for specific subgroups of non-malignant diseases requiring a reduced risk of toxicities, offering the opportunity to discuss the essential points for achieving patients' long-term survival after MRD HSCT in BMF. "
3.	Biomarkers (Surrogate Marker)IBA 01/01/2020 - "Diagnosis of IBMFS presents a major challenge due to the large variety of associated phenotypes, and novel, clinically relevant biomarkers are urgently needed. " 02/01/2012 - "The further characterization of the pathways leading to IBMFS is likely to reveal novel targets for screening tests, prognostic biomarkers, and improved and specific therapeutics." 03/01/2024 - "This issue of Progress in Hematology covers four topics related to aplastic anemia: (1) laboratory markers to identify immune pathophysiology and their role on differential diagnosis and prognosis, (2) the path to combination therapy with horse anti-thymocyte globulin, cyclosporine A, and eltrombopag, (3) more than 60 years of history and recent trends in allogeneic HSCT, and (4) genetic testing for differential diagnosis from IBMFS and novel approaches to transplantation for children including fludarabine/melphalan-based conditioning."
4.	AndrogensIBA 01/01/2020 - "Androgen therapy in inherited bone marrow failure syndromes: analysis from the Canadian Inherited Marrow Failure Registry." 01/01/2020 - "Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS." 01/01/2020 - "Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. " 01/01/2022 - "Nuclear magnetic resonance (NMR) was used to evaluate serum lipid profiles, and lipoprotein particle number and size in nine androgen-treated individuals with DC, 45 untreated individuals with DC, 72 unaffected relatives of DC patients, and 19 untreated individuals with a different inherited BMF syndrome, Fanconi anaemia (FA). "
5.	VaccinesIBA 02/26/2014 - "Thus, antibody responses to the HPV L1 VLP vaccine in patients with FA and other IBMFS appeared to be similar to the responses reported in the general population, implying potential efficacy against future infections with the HPV types contained in the vaccine. "
6.	thymoglobulin FDA Link 10/01/2023 - "The paper by Alsultan et al. report the safety and efficacy of MRD HSCT conditioned with low-dose cyclophosphamide, fludarabine and thymoglobulin in both aSAA and non-Fanconi iBMFs, strengthening the concept of the pivotal role of immunosuppressive approach in allo-HSCT for specific subgroups of non-malignant diseases requiring a reduced risk of toxicities, offering the opportunity to discuss the essential points for achieving patients' long-term survival after MRD HSCT in BMF. "
7.	DiamondIBA 01/01/2021 - "The diagnostic evaluation of Diamond Blackfan Anaemia (DBA), an inherited bone marrow failure syndrome characterised by erythroid hypoplasia, is challenging because of a broad phenotypic variability and the lack of functional screening tests. " 01/01/2017 - "Diamond Blackfan anaemia (DBA) is a congenital bone marrow failure syndrome characterised by selective red cell hypoplasia. " 03/01/2015 - "Diamond-Blackfan anaemia is a congenital bone marrow failure syndrome that is characterized by red blood cell aplasia. " 09/01/2011 - "Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). " 01/01/2017 - "Herein we review the clinical features, underlying biology, and new genomic discoveries in the IBMFS, including Fanconi anaemia, dyskeratosis congenita, Diamond Blackfan anaemia, Shwachman Diamond syndrome and some disorders of the myeloid and megakaryocytic lineages."
8.	Nonsense Codon (Nonsense Mutation)IBA 04/12/2022 - "Eventually, this study may act as a proof of concept for the development of similar approaches for other IBMFS caused by nonsense mutations." 06/30/2020 - "Since approximately 28% of FA, 24% of SCN, 21% of DBA, 20% of SDS, and 17% of DC patients harbor nonsense mutations in the respective IBMFS-related genes, we discuss the use of the nonsense suppression therapy in these diseases. "
9.	tert-butylserineIBA 01/01/2022 - "Two hundred thirty-one individuals with DC/TBDs (144 male, 86.6% known genotype, median age at diagnosis 19.4 years [range 0 to 71.6]), enrolled in the National Cancer Institute's Inherited Bone Marrow Failure Syndrome Study, underwent detailed clinical assessments and longitudinal follow-up (median follow-up 5.2 years [range 0 to 36.7]). " 12/08/2023 - "Telomere biology disorders (TBDs) are a spectrum of inherited bone marrow failure syndromes caused by impaired telomere function due to pathogenic germline variants in genes involved in telomere maintenance. "
10.	Erythropoietin FDA Link 08/01/2013 - "In our study of 97 patients with an IBMFS, increased Hb F was associated with young age, male gender, anaemia, high erythropoietin levels, and alternative alleles in Xmn1-HBG2 [adjusted P = 0·04 for the total group, driven by Fanconi anaemia (P = 0·02) and dyskeratosis congenita (P = 0·09)]. " 08/01/2013 - "Patients with inherited bone marrow failure syndromes (IBMFS) have 'stress erythropoiesis', with anaemia, macrocytosis, increased fetal haemoglobin (Hb F) and high erythropoietin levels. "

Therapies and Procedures

1.	Therapeutics 06/30/2020 - "Unfortunately, no specific pharmacological therapies have been highly effective for IBMFS. " 01/01/2021 - "The development of DC-like hematopoietic stem cells will facilitate the understanding of the molecular and cellular basis of this inherited bone marrow failure syndrome and will serve as a platform to evaluate the efficacy of new hematopoietic therapies for DC." 12/08/2023 - "A major goal for IBMFS is to reduce cellular therapy-related complications to the point that earlier intervention can be considered before significant transfusion exposure, occurrence of comorbidities, or malignant transformation. " 01/01/2022 - "We conclude with a critical assessment of current and future therapies targeting these pathways in inherited bone marrow failure syndromes patients." 01/01/2022 - "Given the genetic complexity and poor prognosis of these inherited bone marrow failure syndromes, there is increasing interest in both characterizing the genetic landscapes of these diseases and developing novel gene therapies to effectively monitor and cure patients. "
2.	Cell Transplantation 07/01/2022 - "Recent advances in hematopoietic cell transplantation for inherited bone marrow failure syndromes." 12/04/2020 - "Hematopoietic cell transplantation (HCT) offers curative treatment of the hematologic complications of IBMFS. " 09/01/2017 - "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." 05/01/2017 - "Current Knowledge and Priorities for Future Research in Late Effects 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 Hematopoietic Cell Transplantation." 01/01/2023 - "Haematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. "
3.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 10/01/2021 - "In recent years, analysis of large series from international databases (mainly from the European Bone Marrow Transplantation [EBMT] database) has improved knowledge about HSCT in IBMFS. " 01/01/2015 - "Although patients with IBMFs are candidates for bone marrow transplantation or gene therapy, their phenotypic heterogeneity can delay or incompetent diagnosis. " 02/01/2010 - "Bone marrow transplantation for inherited bone marrow failure syndromes." 06/01/2014 - "Bone marrow transplantation (BMT) has been used with increasing frequency to treat congenital bone marrow failure syndrome (CBMFs) successfully. " 01/01/2021 - "Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS). "
4.	Stem Cell Transplantation 06/01/2024 - "Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. " 10/01/2023 - "How to optimize outcome of patients undergoing HLA-matched related haematopoietic stem cell transplantation in acquired and inherited bone marrow failure syndromes." 10/01/2013 - "The aim of this study is to examine how uncertainties arising from different sources are associated with decision making regarding stem cell transplantation in Fanconi anemia, a rare, inherited bone marrow failure syndrome that typically presents during childhood. " 06/01/2024 - "HLA-haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties." 12/01/2017 - "In this context, nonmalignant disorders such as bone marrow failure syndromes, inherited genetic disorders and hemoglobinopathies have become the major indication for stem cell transplantation. "
5.	Hematopoietic Stem Cell Transplantation 04/01/2022 - "Poor outcome after hematopoietic stem cell transplantation of patients with unclassified inherited bone marrow failure syndromes." 12/01/2021 - "Hematopoietic stem cell transplantation for inherited bone marrow failure syndromes: alternative donor and disease-specific conditioning regimen with unmanipulated grafts." 10/01/2021 - "Hematopoietic stem cell transplantation for classical inherited bone marrow failure syndromes: an update." 08/01/2017 - "Disease-specific hematopoietic stem cell transplantation in children with inherited bone marrow failure syndromes." 04/01/2016 - "Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes."