FAQ

• The INTO-HLH Registry is a patient registry created for people with hemophagocytic lymphohistiocytosis (HLH) in North America. A patient registry is a study where information about patients is systematically collected to learn more about a particular condition. With INTO-HLH, we plan to gather information about the 'journey' (the diagnosis, treatment, and outcomes) of patients with HLH.
• The aim of this Registry is to gather more comprehensive information about HLH, including the impact of this condition, complications, and its treatment responses. The ultimate goal is to improve diagnosis, treatments, and hopefully, the prognosis for these patients.

• In recent years, physicians are increasingly recognizing HLH and researchers have gained an improved understanding of HLH. However, due to the rarity of the condition and limited information about what happens to these patients before and after treatment, understanding of HLH is incomplete. As a result, consistent and detailed information from a large number of patients with HLH is needed to better understand this disorder.
• This Registry will collect information on HLH from patients' medical records and their routine clinical care before the beginning of the condition and for at least five years after the end of treatment. This information will include the causes leading to the condition, its symptoms and treatments, and the outcome of the treatment. The Registry will also collect information on how HLH impacts patients' daily life.
• Data collected will improve our understanding of HLH. This may help patients and healthcare professionals to make more informed decisions in the future about treatment options for HLH and ways to manage this condition.

All pediatric patients (minors) and adult patients in North America with clinically confirmed or suspected HLH disorders are eligible to participate. We are seeking to enroll patients with all forms of HLH, including and not limited to primary HLH, secondary HLH, and macrophage activation syndrome (MAS), and cytokine release syndrome (CRS).

• Currently, there is no fixed end date of data collection for this Registry. However, we expect that all participants will be able to share their information for at least 5 years. Clinical information will be collected by a specialized team at Cincinnati Children's Hospital, called the INTO-HLH Registry Team (IHRT).
• You or your loved one will also have the option to share their experience with HLH by completing online questionnaires.

• You or your loved one can enroll by visiting the registry website (www.hlhregistry.org). There, you will be able to learn more about the Registry. You will also be asked a few questions to determine whether the Registry is right for you.
• If you agree and are eligible, you will be asked to sign a consent form. A consent form is a document that describes the purpose of the Registry and what you will have to do while in the Registry. By signing the consent form, you agree to participate in the Registry and allow the IHRT to access your medical records.
• Participants younger than 18 years of age will need their legal guardians to sign a consent form for them before joining the Registry.

• Name
• Contact information
• Date and location of birth
• Other demographic data: Gender and ethnicity

Clinical data, such as family history, other diagnosed conditions, results from routine testing, treatment history and outcomes, HLH- and treatment-related complications, and other information, would be taken directly from the medical chart.

You may also share your personal experience with HLH via optional periodic surveys

• Yes, families (including legal guardians or representatives) of deceased patients can share their loved one's data with the Registry.
• Families and legal guardians will follow the same process listed above.

• Yes, in addition to information from medical records, we are gathering samples from patients (such as blood samples, cheek swabs, biopsy samples, etc.) to better understand what happens during HLH
• When genetic causes of HLH are not known, we may conduct genetic studies on these samples

• No. The INTO-HLH Registry is an "observational" study. This means the routine care of participants will simply be observed or studied to better understand the condition.
• Participants will not be required to take any medications or attend any additional visits that are not part of their regular care.

• There is a very low risk to participants as no investigational drug, device, or other intervention will be given to participants as part of this Registry.
• Steps have been taken to help ensure that your or your loved one's personal information remains confidential. Privacy and personal information will be protected following the guidelines and requirement applicable in your country. You should expect that any information about you or your loved one that is collected and used during this study will remain confidential.
• All paper documents (for example, original medical records) will be stored within a locked filing cabinet located in the IHRT offices at the Cincinnati Children's Hospital Medical Center (CCHMC).
• Electronic medical record data will be securely sent to the INTO-HLH database. All transmission to and from the database is encrypted and password protected.

• No, a unique coded number, called a Global Unique Identifier (GUID), will be assigned to each participant's medical record information when stored in the INTO-HLH database.
• This unique GUID code will be used instead of directly identifiable information, thereby protecting the participant's identity.

• To ensure all data privacy requirements are met, the INTO-HLH Registry was conceived and designed to adhere to:
  • the 1996 Health Insurance Portability and Accountability (HIPAA) Act or the Personal Health Information Protection Act (PHIPA), depending on the country and
  • all Good Clinical Practice (GCP) regulations and rules.
• Access to participants' protected health information will be limited to selected and qualified study personnel:
  • Principal Investigator
  • IHRT at CCHMC
• The registry collaborators will have access to anonymized registry data for scientific and regulatory purposes only.

• Your (or your loved one's) data will be collected in 4 different ways:
  • Medical Record entries, where the IHRT will request and analyze data from participants' medical records.
  • Patient Portal, where participants can fill in surveys and share their own experiences living with HLH.
  • Physician Portal, where doctors can enter data about participants with HLH under their care.
  • Biological sample bank. If you agree to contribute samples to the Registry, the IHRT will request biological samples from participants.

• No individual participant's data will be published, nor will individual participants be identifiable from published registry results.
• Individual participants data is aggregated and the results from the Registry's data will be used for scientific and regulatory purposes only.
• This will be communicated via registry reports and publications (that is, conference abstracts and journal manuscripts).

• Unfortunately, we are not able to selectively gather information. However, patients taking part in the Registry will be given a choice to share only clinical data and not biologic samples.

• The first analysis of the Registry should be available in 2024.

• There is no monetary compensation for participating in this Registry.

• A participant or their legally authorized representative(s) can choose to withdraw consent given to the registry at any time.

• The Histiocyte Society's HLH Registry is an international registry aimed to assess the feasibility and design of future international clinical studies. It mainly focuses on primary HLH and gathers limited information. The INTO-HLH Registry is open to individuals in North America and focuses on all types of HLH. It aims to obtain much more comprehensive information on HLH and broadly improve the understanding of the condition and its treatments.

If you have questions, concerns, or complaints or need additional information regarding participating in this Registry at any point, feel free to contact a member of the IHRT at intohlh@cchmc.org.

Dr. Michael Jordan, the Principal Investigator for INTO-HLH Registry (email: Michael.Jordan@cchmc.org), will be happy to address any further questions.