Forum Posts

Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Peter, now 15, has been a lifelong patient at Lucile Packard Children’s Hospital. He needed a heart transplant at the age of two, and suffered from chronic ear infections, a broken leg, repeated bouts of pneumonia, and a challenging genetic lung disorder (primary ciliary dyskinesia). At the age of eight, he developed a very rare cancer — angioimmunoblastic T-cell lymphoma. Standard cancer treatments were not working on Peter’s lymphoma and he suffered multiple relapses. He needed a stem cell transplant but having already received a heart transplant made it more difficult to introduce another immune system from a separate donor. In 2017, Peter received an αβ haplo-HSCT from his mother. Today—two years later—Peter’s a sophomore in high school who enjoys playing video games with friends, practicing for his driving test in parking lots, excelling at school, and thinking about his future career and personal interests. And for the first time, his lymphoma is on molecular remission. Despite marked improvement in the treatment of children affected by haematological malignancies with chemotherapy, a significant proportion of patients still require HSCT. Haploidentical transplantation opens the possibility to offer this treatment to every child in need of an allograft lacking an HLA-matched sibling, a matched unrelated donor, or a suitable umbilical cord blood unit. However, early attempts at haploidentical HSCT in leukaemia patients were associated with high rates of graft rejection and GvHD, leading to high transplant-related mortality and, consequently, poor survival. In the last two decades, novel insights in transplant immunology, continuing advances in graft-manipulation technology, and improved supportive care strategies have led to significantly better outcomes, so that, with further refinements, it is possible that haplo-HSCT become the preferred transplant option for children with hematologic malignancies without an HLA-identical relative. In order to remove T cells, responsible for GvHD, and B cells, from which post-transplant lymphoproliferative disease (PTLD) can arise, positive selection of CD34+ hematopoietic stem cells (HSCs) has been employed for many years in haplo-HSCT. Although the administration of CD34+ cell megadoses has been demonstrated to be a valid approach for preventing both graft failure and severe GvHD in haplo-HSCT recipients, removal of lymphoid cells and committed hematopoietic progenitors from the graft cause prolonged lymphopenia and delay immune reconstitution, resulting in an increased risk of non-relapse mortality (NRM), mainly from opportunistic infections. In order to circumvent this delay in immune recovery, in 2010, a more sophisticated method of graft manipulation based on selective depletion of ab T lymphocytes, and of B cells (ab haplo-HSCT) was developed. This refined technique of graft engineering reduces the problems associated with delayed immune recovery, which is typical in the CD34+ cell selection approach. Indeed, using ab haplo-HSCT, it is possible to transfer to the recipient not only donor hematopoietic stem cells but also committed hematopoietic progenitors, as well as mature NK and gd T cells. These lymphocyte subsets may provide a protective effect against both leukaemia relapse and severe infections. Human gd T cells orchestrate both innate and adaptive immunity and, unlike ab T cells, recognise tumours in a MHC-independent manner without causing GvHD, giving them immense clinical appeal. Both NK and gd T cells exert a potent antileukemia effect able to prevent the risk of relapse after HSCT. The author recently validated her single-centre results in a multi-centre setting, conducting a retrospective comparative analysis within 13 Italian centres. Evaluating 245 matched unrelated donor (MUD) and 98 ab haplo-HSCT recipients we demonstrated that: first, this approach is associated with a cumulative incidence of NRM and disease recurrence comparable to that of children transplanted from a fully MUD. Second, ab haplo-HSCT abrogates the risk of developing severe acute GvHD and is also associated with a faster neutrophil and platelet recovery than MUD-HSCT. Finally, when compared to a mismatched unrelated donor HSCT, αβ haplo-HSCT is clearly superior, showing a significantly lower NRM and a better chronic GvHD-free/relapse-free survival (GFRS). In light of all these considerations, αβ haplo-HSCT represents the ideal platform for post-HSCT adoptive immunotherapy for treating either malignant or non-malignant disorders. https://insights.omnia-health.com/laboratory/latest-developments-treating-siod
0
0
2
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
In 2018, Lucile Packard Children’s Hospital (LPCH) at Stanford welcomed two siblings with Schimke immuno-osseous dysplasia (SIOD), an extremely rare form of dwarfism that affects just seven children in the U.S. The two siblings, Kruz and Paizlee Davenport, are the first brother and sister pair with SIOD in the country to become ambassadors for the condition. “There was a one in 80 million chance both Kruz and Paizlee would have SIOD,” says their mother, Jessica. Today the siblings are both being treated at LPCH, where they are receiving a ground-breaking treatment combining stem cell and kidney transplant from their HLA-partially matched parents. This innovative approach, which eliminates the use of post-transplant immunosuppressive drugs, is being overseen by a multidisciplinary team led by the author. Children with SIOD have a life expectancy of 11 years and normally experience conditions such as kidney failure, severe T-cell deficiency, and hip dysplasia. So far, only five patients in the world have been reported to receive both a stem cell and kidney transplant. Four patients died because of post-transplant complications including severe graft-versus-host disease (GvHD). The fifth patient, Kruz, has fully recovered from a living donor kidney transplant that took place in July 2019, five months after the stem cell transplant where his mother Jessica was the donor. Paizlee, the younger sister, is now three months out of a paternal stem cell transplant and will receive the kidney from the father early next year. These siblings are benefiting from a method of graft engineering pioneered by the author that makes it safer to receive stem cells from a donor who does not have an exact HLA match. In fact, to overcome the mismatch between donor and recipient, a novel method of ex vivo T- and B-cell depletion based on the selective elimination of αβ+ T cells (the lymphocyte subset responsible for GvHD occurrence) was implemented. After this manipulation, the graft contains not only hematopoietic stem cells (i.e. CD34+ cells), but also large numbers of effector cells such as Natural Killer (NK) cells and gd T cells. These lymphocyte’s subsets, promptly available after the transplants infusion, can effectively control severe infections and leukaemia recurrence. Using this graft manipulation’s strategy, the extensive depletion of αβ+ T cells (up to 5 logs) abrogates the risk of severe GvHD. Thanks to this approach, a donor is virtually available for every patient in the need of a transplant. A fully matched related donor (sibling), is present in the family for only 25 per cent of the patients, and less than the remaining 60 per cent can allocate a suitable unrelated donor in an acceptable frame time. The likelihood of finding an optimal donor, varies among racial and ethnic groups, with the probability of identifying an appropriate donor being highest among whites of European descent (75 per cent) and lowest among blacks of South or Central American descent (16 per cent). Thus, there is an urgent clinical need for more broadly applicable hematopoietic stem cell transplant (HSCT) methods that can reach a wider range of patients. Such a development has a major medical impact in patients lacking a fully matched donor, a situation that is especially true for ethnic minorities. However, this is not only a donor’s matter. The fast and robust neutrophil and platelet engraftment (13 and 11 days, respectively), the absence of the need of post-transplant pharmacological GvHD prophylaxis as well as the negligible risk of chronic GvHD, render this approach ideal for indications previously not for candidates for transplant due to the high burden of complications. SIOD is just one of the multiple different diseases that now can be treated with an αβ haplo-HSCT. Remarkably , the exciting result of this pilot experience combining stem cell and kidney transplantation from the same donor, has laid the foundation at Lucile Packard Children’s Hospital for expanding the use of αβ haplo-HSCT to diseases routinely not for candidates for allogeneic HSCT, to patients in very poor clinical condition and in the need of living donor solid organ transplant. - Omnia Health Insights https://insights.omnia-health.com/laboratory/latest-developments-treating-siod
0
0
6
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Graft-versus-host disease is one of the most common complications of stem cell transplantation. Stanford’s Maria Grazia Roncarolo, MD, and her team have launched a clinical trial to test whether T-cells can help prevent graft-versus-host disease after stem cell transplantation. This trial is only available at Lucile Packard Children’s Hospital Stanford. Watch the video here: https://youtu.be/EupkJjsrV0s
0
0
0
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
We recognize that stem cell transplantation places enormous emotional, financial, psychological and logistical burdens on patients and families. In addition to a dedicated inpatient and outpatient nursing staff, the program provides multifaceted support for patients and families, including dedicated social workers and child life specialists; a hospital-based school; physical, occupational and speech therapy; and spiritual support. Our social workers also conduct group therapy sessions for families. The hospital-based school is a unique collaboration between the hospital and the Palo Alto Unified School District that permits young patients to continue their schoolwork during transplantation and aids in their transition back to their original school. In addition, the newly renovated Ronald McDonald House is available for housing patients and families. A shuttle is available to transport patients and families between the house and the hospital. Contact us online or call (650) 497-8953 for more information.
0
0
2
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Hematopoietic stem cell transplantation can be a curative therapy for children and young adults with immunological, hematological and metabolic diseases as well as for patients with cancers who have not responded to standard chemotherapy. The Pediatric Stem Cell Transplantation program was established at Lucile Packard Children’s Hospital Stanford in 1986. Since then, we have transplanted more than 900 patients. The program is housed in a 12-bed Stem Cell Transplant Unit with HEPA-filtered air and a dedicated nursing staff on the first floor of Lucile Packard Children’s Hospital Stanford. The program is growing and will move to a new 24-bed unit. Now that the Stanford Laboratory for Cell and Gene Medicine is open, the program is capable of producing cells required for both cellular and gene therapies. The program is an active member of the Children’s Oncology Group, the Pediatric Bone Marrow Transplantation Consortium and the Bone Marrow Transplantation Clinical Trials Network. Our stem cell transplant patients are treated on either standard of care protocols or investigational protocols for diseases and conditions that have no established therapies. The investigational protocols have all been approved by both the Food and Drug Administration (FDA) and the Stanford Investigational Review Board. The program’s attending physicians are all board-certified physicians with accreditation in hematology, oncology and/or immunology, and all are certified by the Foundation for the Accreditation of Cellular Therapy (FACT). Our principal goals are: Improving the effectiveness and safety of stem cell transplantation Developing approaches to treat patients and diseases that cannot currently be successfully treated by stem cell transplantation We are currently developing several innovative theories, including: An antibody-mediated preparative regimen for hematopoietic stem cell transplantation that does not require either chemotherapy or irradiation, thereby eliminating the side effects associated with the use of chemotherapy and irradiation Regulatory T lymphocytes (TR1 cells) that are being evaluated for their ability to prevent acute graft-versus-host disease in mismatched stem cell transplantation Innovative preparative regimens with reduced or no doses of cyclophosphamide to reduce or eliminate the side effects associated with cyclophosphamide With the opening of the Stanford Laboratory for Cell and Gene Medicine, clinical Phase 1, proof-of-concept trials using gene editing and gene transfer techniques are under development to treat patients with diverse diseases, including: Patients with sickle cell anemia, who will be treated by the transplantation of autologous hematopoietic stem cells that have been edited to replace the sickle cell anemia gene with the normal hemoglobin gene Patients with IPEX syndrome, a genetic immunodysregulatory disease, who will be treated by the infusion of autologous T lymphocytes that have been transduced with a lentiviral vector containing the normal FOXP3 gene followed by the transplantation of autologous hematopoietic stem cells transduced with the same FOXP3-containing lentiviral vector Patients with acute myelogenous leukemia, who will receive TR1 cells as a means to reduce acute graft-versus-host disease and also as immunotherapy for their acute myelogenous leukemia Pre-clinical and developmental research has been undertaken by the members of the Division of Stem Cell Transplantation and Regenerative Medicine and other scientists at Stanford University. The Stanford Laboratory for Cell and Gene Medicine makes it possible for pre-clinical research to be directly translated into Phase 1, proof-of-concept clinical trials at Lucile Packard Children’s Hospital Stanford. The clinical stem cell transplant of each patient is determined by the patient’s disease, the source of the hematopoietic stem cells used for transplantation, the stem cell donor and the patient’s prior clinical history. The stem cell donor can be the patient themselves (autologous) or someone else (allogeneic). The stem cells can come from bone marrow, peripheral blood or cord blood. The patient’s disease and clinical history will determine the specific therapy that he or she receives prior to transplantation. Patients are usually hospitalized for 1 to 2 months depending upon their clinical status. After their discharge, patients will have follow-up visits in the outpatient clinic, including the long-term follow-up clinic.
0
0
1
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
We offer a chance at a cure of the kidney disease and immune problems with our novel duo-transplant technique. We are also experts at what we do. Stanford Children’s Health has performed over 1000 stem cell transplants since the program’s inception. Our program on alpha/beta T-cell depletion is the biggest in the country. We also participate in groundbreaking research in SIOD. Immunologist David B. Lewis, MD heads up our SIOD research lab (in partnership with the Kruzn for a Kure Foundation), which is working to understand the cause of SIOD and its effects on the body, including its immune response (T cells). He is part of a team of researchers across the world studying SIOD. Defects in the DNA code for the SMARCAL1 gene result in SIOD. The SMARCAL1 gene encodes a protein that helps DNA copy itself efficiently. This ability is very important, since our bodies constantly replace and renew cells throughout the body. Dr. Lewis and others are studying how the genetic deficiency of SMARCAL1 relates to the symptoms of SIOD and investigating related treatments to help heal children with SIOD. Finally, when children with SIOD come to us, they receive care from a multidisciplinary team of internationally and nationally respected stem cell and kidney transplant specialists, nephrologists, neuroimmunologists, oncologists, and other specialists. We give hope to parents who experienced little before.
0
0
1
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
This novel treatment approach is potentially a cure for SIOD. When a new immune system is adopted from a donor—one that recognizes the transplanted kidney as its own—the possibility of chronic rejection of the kidney appears to be eliminated, along with the need for long-term medication. The body is no longer in a state of constantly fighting itself, and children treated with this method are experiencing more energy and less fatigue. By removing the need for medication, doctors also remove toxicities associated with these medications. Without medications and long hours of dialysis, quality of life for children is often improved.
0
0
0
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Finding a fully matched stem cell donor is often a challenge, leaving children to wait sometimes years for a donor. Instead, our doctors use a partially matched donor who is more readily available, usually a parent. We then selectively eliminate alpha/beta T cells (the immune system’s fighter cells) from the donor’s stem cells to reduce the risk of graft-versus-host disease, which is otherwise a frequent complication of these kind of transplants. This revolutionary stem cell transplant method is led by Alice Bertaina, MD, PhD—the worldwide pioneer and foremost expert in alpha/beta T-cell depleted haploidentical stem cell transplantation.
0
0
0
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Our physician-scientists are studying a novel approach to treating SIOD that’s a potential cure for the kidney disease and immune problems caused by SIOD. This treatment is a two-transplant approach—a haploidentical stem cell transplant, which provides your child with a new immune system, followed by a kidney transplant from the same donor, usually a parent. Since your child’s new immune system recognizes its new kidney, it is less likely to reject it. Have you tried this approach with other children? How are they doing? Of the first three children treated with this method at Stanford Children’s Health, all three were successfully transplanted and all three achieved full donor engraftment—meaning the transplanted stem cells grew into healthy cells, including those that are part of the immune system.. The three children, two of whom are siblings, achieved normal kidney function without the use of long-term anti-rejection medicines.
0
0
1
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
When a child receives a transplanted organ, such as a kidney, he or she is given anti-rejection medication to reduce the risk of rejection of the graft. Medications are used to suppress the immune system to keep it from rejecting the donated organ. Yet this constant battle between the immune system of the body and the transplanted organ may lead to loss of the transplant after only 10-12 years even if the transplant recipient reliably takes immunosuppressive medications. Our unique approach to treating SIOD (and certain other diseases) appears to solve this dilemma.
0
0
0
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Traditional treatment for SIOD involves simply managing symptoms. When kidney failure progresses, children must receive dialysis and eventually a kidney transplant to stay alive. Stem cell transplants can also be used to treat immunodeficiency and blood abnormalities.
0
0
0
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Nearly all children with SIOD are short-statured, the first obvious sign. Short-stature is caused by a skeletal disorder called spondyloepiphyseal dysplasia, where the bones in the spine, arms and legs do not fully develop. A doctor might also notice that your child is failing to grow properly or has immune system problems (i.e. a T-cell deficiency leading to a weak immune system that leaves your child vulnerable to serious infections). Fatigue and kidney disease are also common signs of SIOD.
0
0
1
Kruzn for a Kure Foundation
Feb 08, 2022
In Questions & Answers
Schimke immuno-osseous dysplasia (SIOD) is an extremely rare genetic disease that affects multiple systems in the body, including the kidneys, growth plates and cartilage, heart and arteries, lungs, and immune system. SIOD occurs when both a mother and father carry an abnormal gene. It affects approximately 1 in 1-2 million babies born in North America. SIOD is either severe with early-onset symptoms starting as an infant, or mild with late-onset symptoms starting in the teen years.
0
0
0
Kruzn for a Kure Foundation
Jan 21, 2022
In General Discussion
Share your thoughts. Feel free to add GIFs, videos, #hashtags and more to your posts and comments. Get started by commenting below.
0
0
7
Kruzn for a Kure Foundation
Jan 21, 2022
In General Discussion
We'd love to get to know you better. Take a moment to say hi to the community in the comments.
0
0
3
Kruzn for a Kure Foundation
Jan 21, 2022
In General Discussion
We want everyone to get the most out of this community, so we ask that you please read and follow these guidelines: Respect each other Keep posts relevant to the forum topic No spamming
0
0
4
K
Kruzn for a Kure Foundation

Kruzn for a Kure Foundation

Admin
More actions