Bone Marrow Failure Disorders

This website, developed with support from Alexion Pharmaceuticals, Inc, features an infogram highlighting the typical signs, symptoms, and disease burden in patients with paroxysmal nocturnal hemoglobinuria.

This review, published in Trends in Pharmacological Sciences, describes preclinical and clinical studies of agents in the compstatin family and offers expert discussion of potential future applications of this drug class in complement diseases. In 2021, the authors note, pegcetacoplan (Empaveli/Aspaveli), a PEGylated, second-generation compstatin derivative, was approved for the treatment of paroxysmal nocturnal hemoglobinuria and is now being evaluated for possible additional indications.

In this recent literature review published in Expert Opinion on Emerging Drugs, European investigators used Medline and ClinicalTrials.gov databases to evaluate new drugs now in phase 2 and 3 trials for adults with paroxysmal nocturnal hemoglobinuria (PNH). The review discusses novel terminal complement inhibitors (targeting C5) and proximal complement inhibitors (interfering with C3 and upstream factors B and D) under investigation for the management of PNH. In their expert opinion, the authors write: "Ravulizumab is the first next-generation C5 inhibitor, approved by FDA and EMA, which reproduced the excellent results achieved with eculizumab, trying to improve the convenience of patients. However, unresolved issues remain, such as C3-mediated extravascular hemolysis, on which novel proximal complement inhibitors are showing their efficacy. Pegcetacoplan is the first C3-inihibitor approved by FDA. Long-term safety data for novel complement inhibitors are needed."

This up-to-date resource from Everyday Health is helpful for patients with newly diagnosed paroxysmal nocturnal hemoglobinuria (PNH). Besides highlighting PNH causes and risk factors, symptoms and diagnosis, and current treatment options, there are tips for traveling; managing emotional aspects of living with PNH; and finding PNH specialists, support networks, and other resources.

Produced by the Nurses Group of the European Society for Blood and Marrow Transplantation (EBMT NG), this PDF brochure on paroxysmal nocturnal hemoglobinuria (PNH) was published in 2015 (with financial support from Alexion Pharmaceuticals). While discussion of treatment options may be dated, there is still useful, detailed, and well-organized information about PNH signs, symptoms, causes, diagnosis, and management, from a nursing perspective.

The Genetics section of MedlinePlus offers patient-friendly information about characteristic symptoms of paroxysmal nocturnal hemoglobinuria (PNH) and its causes, including detailed information about how mutation of the PIGA gene causes PNH. Links to genetic testing information, PNH patient support and advocacy resources, and current clinical trials are provided.

In a retrospective, longitudinal cohort study of 151 patients with paroxysmal nocturnal hemoglobinuria (PNH), investigators evaluated the real-world economic burden and treatment patterns of transfusion-dependent (n=55) vs transfusion-free (n=96) users of the C5 inhibitor eculizumab. After analyzing nationally representative, administrative claims data from a US population, they concluded that "[t]he economic burden of patients with PNH treated with eculizumab is greater among those dependent on blood transfusions," adding that "blood transfusion dependence may serve as an important indicator of uncontrolled disease … among patients with PNH."

The MSK Kids website of Memorial Sloan Kettering Cancer Center offers reader-friendly clinical snapshots on Fanconi anemia, CAMT (congenital amegakaryocytic thrombocytopenia), DBA (Diamond-Blackfan anemia), dyskeratosis congenita, GATA2 deficiency, Shwachman Diamond syndrome, and TAR (thrombocytopenia absent radii) syndrome.

This 3.5-minute animated video (produced by Springer Nature with support from Alexion Pharmaceuticals, Inc.) provides an overview of the etiology and symptoms of paroxysmal nocturnal hemoglobinuria (PNH), and highlights management of PNH with C5 inhibitors.

In this whiteboard-style, 4-minute video, a clinical hematologist reviews the pathophysiology, clinical symptoms, laboratory testing, diagnosis, and management relevant to paroxysmal nocturnal hemoglobinuria.

This 3-minute computer-animated video (produced with support from Agios Pharmaceuticals, Inc.) provides a useful overview of the mechanisms by which pyruvate kinase deficiency develops, along with the clinical impact of this disorder and possible treatment.

This concise, medically reviewed guide from Everyday Health offers useful travel tips for patients with PNH—including advice on airline travel, ways to make accommodations safer, how families can prepare for visits from loved ones with PNH, and strategies to help patients minimize unnecessary exposures to infection.

In January 2020, the National Organization for Rare Disorders (NORD) and the Foundation for Rare Blood Diseases released this PKD-focused Voice of the Patient report, summarizing perspectives of patients with PKD and their caregivers who participated in a September 2019 externally led patient-focused drug-development (EL-PFDD) meeting. The purpose of the EL-PFDD meeting was to gather information about patient experiences with PKD, quality of life (QoL) issues, aspects of living with PKD that are most problematic for patients, and what actions patients currently take to treat and cope with their disease.

Through their clinical medical knowledge base, eMedicine, Medscape offers current, comprehensive information about PNH, from its pathophysiology, etiology, and epidemiology; to typical presentations and differential diagnoses; to patient workup, treatment, and follow-up. There are also Practice Essentials, Questions & Answers, Media Gallery, and References sections.

In May 2021, the National Organization for Rare Disorders (NORD) and the Aplastic Anemia & MDS International Foundation (AAMDSIF) presented this 24-minute webinar. Participants from NORD and AAMDSIF provide background information about resources that their organizations offer to patients and healthcare professionals; review NORD’s IAMRARE^® Registry Program and data gathering for patient registries for natural history studies; and explain Global PNH Registry data collection aims and processes for storage and use.

MedlinePlus Genetics, a part of the National Library of Medicine’s consumer resource MedlinePlus, offers patients solid information about the etiology of pyruvate kinase deficiency (and many other genetic disorders), plus vetted resources for genetic testing and appropriate clinical trials.

Patient Worthy, an online advocacy and information website for people with rare diseases, recently launched their Rare Classroom series. Featured in July is a reader-friendly post on PNH, with bulleted descriptions providing essential information about its etiology, causes, symptoms, and treatment, as well as links to relevant newsbriefs, research, and national organizations.

This comprehensive 2018 booklet for patients also provides useful information for healthcare providers who are not specialists in the management of PKD. The publication was independently developed by S. Karger Publishers Limited, with the support of an educational grant from Agios.

The CDMRP, created in 1992, is a partnership between the public, the US Congress, and the military. This February 2021 pamphlet highlights current high-impact BMF clinical research, including a link to summary abstracts and publication citations for studies funded through the Bone Marrow Failure Research Program.

While the management of COVID-19 continues to evolve, these recommendations from the European Society for Blood and Marrow Transplantation provide useful guidance on stem cell transplant (HCT) in the context of COVID-19.

Marrowforums was founded by volunteers for, and board members of, the nonprofit Aplastic Anemia & Myelodysplastic Syndromes International Foundation, as a forum for patients with BMF diseases such as AA, MDS, and PNH and their extended support system (family members, friends and caregivers, healthcare professionals). In addition to hosting discussion groups, the website provides links to medical information, clinical trials, and patient advocacy resources.

The goal of 30-year-old Be the Match is to connect patients with donor matches for life-saving adult bone marrow or umbilical cord blood transplants. Be the Match is operated by the National Marrow Donor Program® (NMDP), a nonprofit organization that matches patients with donors, educates healthcare professionals, and conducts research through its Center for International Blood and Marrow Transplant Research®. In an April 2021 news release, the organization noted that since its inception, it has facilitated more than 105,000 transplants for patients with leukemia, lymphoma, sickle cell disease, and approximately 70 other diseases.

The NIDDK website offers user-friendly sections including Definition & Facts; Symptoms & Causes; Diagnosis; Treatment; Eating, Diet, & Nutrition; and Clinical Trials. Information about related conditions and diseases, as well as related research into hematologic diseases at NIDDK, is also provided.

The European School of Haematology, or ESH, held its first translational research e-conference on bone marrow failure disorders live online from November 13–15, 2020. Peruse the website for free access to e-posters, as well as detailed study summaries in the 142-page online scientific program book.

Because inherited bone marrow failure (IBMF) syndromes are associated with a high risk of cancer, researchers and clinicians at the National Cancer Institute have studied patients with IBMF for several decades, and have recently uncovered several new genetic causes of IBMF. The NCI Inherited Bone Marrow Failure Syndrome Cohort Study enrolls families with one or more members with an IBMF syndrome, and includes first-degree and other relatives as appropriate.

The authors of this StatPearls e-book focus on inherited bone marrow failure (BMF) disorders, with sections including but not limited to etiology and pathophysiology, evaluation and management, differential diagnoses, patient education, and clinical pearls related to several common BMF syndromes.

The website of this highly rated charitable organization provides education (patient guides, fact sheets, research summaries) and advocacy resources related to benign hematologic malignancies including aplastic anemia, paroxysmal nocturnal hemoglobinuria, and related bone marrow failure disorders.