Shwachman-Diamond Syndrome

Researchers are evaluating a reduced-intensity preparative regimen for hematopoietic stem cell transplantation in children and young adults with non-malignant disorders. This approach aims to maximize immune suppression without using radiation or high-dose chemotherapy, intending to reduce early and late toxicities. The study also focuses on preventing complications like graft-versus-host disease (GVHD) by using specific prophylaxis methods during matched and mismatched donor transplants from bone marrow and cord blood sources. The trial includes different groups based on the type of non-malignant disorder and the donor match. Treatments involve drug regimens such as Campath, Fludarabine, Melphalan, and sometimes Thiotepa, given before transplantation to prepare the body. GVHD prevention drugs like Tacrolimus, Cyclosporine, Mycophenolate mofetil (MMF), Abatacept, and Methotrexate are administered on specific days before and after the stem cell infusion, which occurs on day 0. Participants will be closely monitored for donor cell engraftment and major toxicities within the first 100 days after transplant. Assessments include measuring blood counts for neutrophil and platelet recovery, tracking acute and chronic GVHD occurrences up to two years post-transplant, and evaluating immune recovery one year after transplant. Overall and disease-free survival will also be followed for two years. The study spans from preparative treatment through long-term follow-up, with safety and effectiveness monitored at regular intervals.

Researchers are studying Inherited Bone Marrow Failure Syndromes (IBMFS), including Fanconi Anemia and others, to understand the types and rates of cancer in these conditions. The study aims to identify how genetic changes in IBMFS contribute to cancer development, differences between patients who develop cancer and those who do not, and cancer risks for carriers of IBMFS gene variants. This natural history study helps provide important information for cancer screening and prevention in families at higher genetic risk. The study involves families with members affected by IBMFS, including patients and their relatives such as siblings, parents, and grandparents. It collects information through questionnaires, clinical and research evaluations, laboratory tests, medical record reviews, and ongoing cancer surveillance. Participants include those with confirmed IBMFS diagnoses or those suspected based on symptoms or genetic tests, as well as individuals from the general population with certain cancers but without usual risk factors. Participants will undergo regular assessments including clinical exams, laboratory tests, and reviews of medical history to monitor cancer development and related conditions. Researchers will measure outcomes such as the occurrence of all cancers, solid tumors, and cancers specific to each IBMFS type, along with markers of pre-cancerous conditions. This ongoing study aims to better understand cancer risks and biology in IBMFS and carriers, with involvement lasting as long as participants remain in the cohort and continue follow-up.

Researchers are collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation (HSCT) using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants: umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physician's guidance at the UPMC Children's Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease (GVHD) and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients' charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Researchers are studying inherited bone marrow failure syndromes and related disorders (IBMFS-RD), which are rare diseases causing serious health problems and early death. This research aims to improve diagnosis by using whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) to better understand these conditions, which are often underdiagnosed due to limited genomic testing. The study will help clarify diagnosis, guide treatment choices, and inform genetic counseling for patients and their families. The study involves performing whole genome and transcriptome sequencing on up to 350 patients suspected of having IBMFS-RD. This observational study will analyze genetic data to increase the diagnostic rate and explore the health and economic impacts of genomic testing. The study will also investigate new ways to classify gene expression and gather data for a registry over a four-year period. Participants will provide samples for genomic analysis and share clinical information during the study. Researchers will review the diagnosis within 3 to 12 months after baseline and assess longer-term outcomes such as cost-effectiveness and health implementation over four years. The study will include genetic counseling and follow-up to monitor diagnostic results and help guide patient care. Participation duration varies as the study collects data and monitors outcomes over several years.

Inherited bone marrow failure syndromes (IBMFSs) are a group of genetic disorders that cause problems with blood cell production, leading to low blood counts. These syndromes can appear at birth or later in life and sometimes involve bone fragility fractures. This research aims to better understand the genetic causes and characteristics of unclassifiable IBMFSs, especially those with bone fragility, to improve diagnosis, treatment, and management of patients and help prevent future complications. The study involves comprehensive genetic testing using whole-exome sequencing to identify mutations linked to IBMFSs. This testing will be performed at specialized institutions in Japan and analyzed for detailed genetic information. The study will include families with at least two generations affected by IBMFSs and bone fragility fractures, inviting multiple family members to participate in genetic testing. Participants will undergo genetic analysis and clinical evaluations to track disease progression, occurrence of fragility fractures, and potential transformation to malignancy over two years. Researchers will monitor these outcomes to better understand the disease course. The study is observational, with no experimental treatment, and participation may involve follow-up visits and data collection over time to gather comprehensive information about the condition.

Researchers are evaluating a new approach to prevent serious viral and fungal infections after allogeneic hematopoietic stem cell transplant (HSCT) from donors who are not fully HLA-matched siblings. This study focuses on adding back CD45RO memory T cells to grafts depleted of T cell receptor alpha beta (TCRb1b2) and CD19+ B cells to reduce the risk of graft versus host disease (GVHD) while improving immune recovery. The trial expands eligibility to patients with both malignant and non-malignant conditions using mismatched related and unrelated donors. The study includes phase 1 and phase 2 periods. Phase 1 is a dose escalation study for patients receiving cells from mismatched or haploidentical related donors, testing increasing doses of CD45RA-depleted addback cells to find the maximum tolerated dose. Phase 2 treats patients with this dose from phase 1 or those with unrelated donors using a previously established dose. Stem cell sources are mobilized peripheral blood stem cells, and conditioning follows disease-specific standard care. Participants will be monitored for acute and chronic GVHD up to 2 years after transplant. Their immune recovery and incidence of viral reactivation will also be evaluated over 2 years. Assessments include standard disease and organ criteria, infection status, and consent procedures. The trial duration and safety are closely observed with regular follow-ups to measure outcomes related to immune function and transplant complications.

Researchers are evaluating a reduced-intensity conditioning (RIC) regimen for patients with non-malignant disorders who need a hematopoietic stem cell transplant (HSCT). This study focuses on diseases such as thalassemia, sickle cell disease, primary immunodeficiencies, metabolic disorders, and other inherited conditions. The goal is to assess if RIC before transplant can improve outcomes by reducing complications and transplant-related mortality compared to the standard myeloablative conditioning. The treatments being studied include a conditioning regimen with Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa given before stem cell transplants from umbilical cord blood, bone marrow, or peripheral blood stem cells. Two groups are involved: one receiving double cord blood transplants for transfusion-dependent anemia or higher rejection risk, and another receiving bone marrow or peripheral blood transplants. The study uses lower chemotherapy doses to prepare patients, aiming to help donor stem cells engraft successfully while decreasing side effects on organs. Participants will be monitored for transplant success and side effects over time, including immune recovery, rates of infections, graft-versus-host disease, organ toxicity, and neurodevelopmental progress for up to one year after transplant. Researchers will also track donor cell engraftment and blood counts. The total participation may last several months to years, with follow-up visits to evaluate long-term outcomes and transplant effectiveness.

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that involves bone marrow failure, multiple medical complications, and an increased risk of leukemia. Patients with SDS-Like syndromes show similar clinical features but do not have mutations in known SDS genes. Due to the rarity of these conditions, there is limited information on their natural history, clinical outcomes with current treatments, and overall management. The SDS Registry was established to collect clinical data and biological samples to better understand these diseases and support the development of improved treatments. The registry collects data from medical records and biological samples such as blood, bone marrow, skin cells, saliva, or discarded clinical materials. Samples are collected during routine clinical care, so participants do not need extra visits or procedures. Family members of patients can also contribute blood samples. The registry is managed by Boston Children's Hospital and Cincinnati Children's Hospital Medical Center and maintains all information securely in a HIPAA-compliant database. Participants provide their medical information and samples over a long period, up to 50 years. The research team studies the natural history, medical complications, treatment outcomes, and genetic causes of SDS and SDS-Like conditions. Education is also provided for patients, families, and the medical community about diagnosis and management. No personal information is shared outside the research team, and there are no interventions or treatments assigned as this is an observational study.

The Shwachman-Diamond Syndrome Global Patient Survey and Collaboration Program (SDS-GPS) provides a secure online platform for patients and families worldwide to share their experiences living with Shwachman-Diamond Syndrome (SDS) and related conditions. The program aims to deepen understanding of SDS, enhance patient lives, and speed up the development of new therapies and cures by gathering patient-reported data. SDS-GPS was created with input from patients, families, advocates, researchers, and clinicians to build a supportive global community that drives research forward. Participants create a free account to enter their information and complete surveys covering topics such as demographics, medical history, treatments, disease progression, care access, and quality of life. These surveys can be completed anytime from home and saved for later. The platform supports multiple languages and allows participants to track their medical appointments, medications, and symptoms. The program collects de-identified data to prioritize research, share knowledge, and connect participants with relevant clinical trials and registries. Throughout the program, participants provide ongoing information about symptoms, genetics, quality of life, and disease burden at baseline and at regular intervals such as every 12 months or multiple times per year. This long-term observational approach helps researchers understand patient needs and outcomes. Participation involves no clinic visits or virtual appointments, and privacy and security are maintained at the highest standards. The program offers early access to new research opportunities and supports participants in sharing information with their care teams as they choose.