#myeloablative conditioning regimen

[rodspurethoughts]

FDA Approves Omisirge, a Cell Therapy for Blood Cancer Patients Undergoing Stem Cell Transplantation

The FDA has recently approved a cell therapy called Omisirge (omidubicel-onlv) for patients with blood cancers who are undergoing stem cell transplantation. This allogeneic cord blood-based cell therapy can help speed up the recovery of neutrophils in the body, a type of white blood cell, and reduce the risk of infection. Omisirge is intended for use in adults and pediatric patients 12 years and…

[bansalhospital]

Bone Marrow Transplantation: Types, Techniques And Procedures

A cutting-edge medical procedure that aids patients with immune- and blood-related problems is bone marrow transplantation. It is a potential treatment that inserts healthy stem cells into damaged bone marrow. As a result, it is extensively utilised to treat illnesses connected to the blood.

If you are seeking for a bone marrow transplant facility, Bansal facility Bhopal will be your finest option because this vital treatment necessitates exceptional proficiency and precision. The haematology department will provide you with the best care possible here thanks to their skilled staff of medical experts and cutting-edge equipment.

Let's start by learning about the various bone marrow transplants.

What Exactly Is a Bone Marrow Transplant?

A miraculous medical operation known as a bone marrow transplant replaces diseased or injured bone marrow with healthy stem cells, potentially saving lives. Additionally, patients with certain forms of cancer, genetic illnesses, and immune system problems have hope thanks to this cutting-edge technique. 

Being able to do Bone Marrow transplants Types  utilising the patient's own stem cells or stem cells from a donor who matches the patient's genetic makeup is wonderful. 

Why Do Bone Marrow Transplants Need to Be Done?

Red blood cells, white blood cells, and other vital cells are produced in the spongy bone marrow. People occasionally have illnesses when this equipment is impacted for a variety of causes. As a result, conditions including anaemia, infections, and even cancer might develop. Bone marrow transplantation can help with that.

By reinfusing patients' bone marrow with healthy stem cells, bone marrow transplantation helps patients regain their ability to produce healthy blood cells. Chemotherapy or radiation therapy are followed by an infusion of stem cells into the patient's bloodstream to complete the procedure. The bone marrow then receives the transplanted stem cells and begins to produce new blood cells.

Bone Marrow Transplantation Methods

It is wonderful to know that there are various bone marrow transplantation options available for patients with diverse needs. This transplantation decision is influenced by things like age, health, and donor compatibility.

Various bone marrow transplant procedures include:

1. Autologous Transplant

Using autologous bone marrow transplantation to treat lymphoma and multiple myeloma is a promising option. Because the patient's own marrow cells are used in the transplant, there is a substantially lower chance of problems than with allogeneic transplantation, making the operation ideal. 

Hodgkin's lymphoma, myeloma, and other cancers are treated with autologous bone marrow transplantation.

Non-Hodgkin lymphoma (NHL)

Blood disorders

2. Allogeneic Transplant

A treatment called allogeneic bone marrow transplantation employs donor stem cells to treat specific malignancies and blood conditions. To prevent issues like GVHD, meticulous matching between the donor and the receiver is necessary. 

3.Transplant of umbilical cord blood

When a suitable donor is not available, this transplantation is a fantastic   alternative. In   this, babies' umbilical cord blood, which is a rich source of  hematopoietic stem cells, can    simply be used to extract stem cells. 

4. Haploidentical Transplant

It accepts stem cells from donors that are just a partially compatible match. Additionally, strategies to lower the risk of GVHD and graft rejection have been established. 

5. Mini Transplant (Transplantation Without Myeloablative Therapy)

In comparison to conventional high-dose conditioning regimens, this novel strategy uses lower doses of chemotherapy or radiation therapy, which is a beneficial development.

The goal of RIC is to minimise the negative effects and toxicity that can result from high-dose conditioning while fostering an environment that is favourable for the effective engraftment of donor stem cells.

Considerations For Selecting A Transplant Type

Considerations for a bone marrow transplant include the patient's age, general health, the availability of donors, and the possibility of graft-versus-host disease.

• The type of disease being treated can have an impact on the transplantation option.

• To decide which choice is best for them, patients and their families should have an honest discussion with their healthcare professionals.

• Being aware that every transplant type has different risks and advantages.

The Method For Selecting Donors Through Matching

1. A sibling or unrelated donor registry can be used to match donors.

2. In some circumstances, a haploidentical or half-matched donor may be employed.

3. Appropriate matching is crucial for successful bone marrow transplantation.

4. In the end, the type of transplant chosen will depend on the availability of donors and the particular needs of the recipient.

The Final Say

Blood disease sufferers require bone marrow transplantation to survive. The three different types of bone marrow transplants—autologous, allogeneic, and syngeneic—each have a different strategy for treating specific diseases.

You can contact or visit the haematology division of Bansal Hospital Bhopal to learn more about bone marrow transplantation. 

About Bansal Hospital

Bansal Hospital is a multispeciality hospital and is one of the leading, reputable and reliable healthcare providers trusted by patients and their families across the region. It has all the major departments, including cardiology, neurology, oncology, orthopaedics, gastroenterology, urology, liver transplant, bone marrow transplantation, nephrology, gynaecology and more. The hospital is equipped with state-of-the-art facilities and technology. It has a team of highly qualified and experienced doctors and medical staff who provide round-the-clock care to the patient.

Visit our website

[pharmaphorumuk]

bluebird bio announces long-term data from CALD gene therapy

bluebird bio has announced new clinical trial data from its gene therapy for patients with cerebral adrenoleukodystrophy (CALD), including long-term follow-up data.

CALD is the most severe form of adrenoleukodystrophy (ALD), a rare, X-linked metabolic disease affecting 1 in 21,000 newborn boys worldwide.

Approximately 40% of boys with ALD will develop CALD1, typically between the ages of three and 12 years.

The disease progresses rapidly in early childhood and if untreated, leads to loss of neurologic function, and eventual death, in most patients.

CALD is associated with six major functional disabilities (MFDs) which severely compromise the ability to function independently, including loss of communication, need for tube feeding and complete loss of voluntary movement.

The company highlighted data presented at the online European Society for Blood and Marrow Transplantation 2021 conference from the Starbeam ALD study involving the gene therapy known as elivaldogene autotemcel, known for short as eli-cel or Lenti-D.

Data from the phase 2/3 Starbeam study show “promising evidence” with up to almost seven years of follow-up, that 31 out of 32  patients showed minimal loss of function following eli-cell infusion.

There were no reports of graft failure, graft rejection, or graft-versus-host disease, where the body’s own immune system reject genetically modified cells.

Dr Jörn-Sven Kühl, Department of Pediatric Oncology, Hematology and Hemostaseology, Center for Women’s and Children’s Medicine at University Hospital Leipzig, said: “These long-term results therefore suggest treatment with eli-cel may durably stabilise disease progression and consequently preserve as much neurological function as possible in boys with CALD.”

Of the 32 patients who have received eli-cel in Starbeam ALD-102, 27 have completed the study and enrolled in a long-term follow-up study (LTF-304).

Two additional patients continue to be followed in ALD-102 and have not reached 24 months post-treatment and one experienced rapid disease progression early on-study resulting in MFDs and subsequent death.

The primary efficacy endpoint in Starbeam is the proportion of patients who are alive and free of MFDs at month 24.

In the first part of the study, 27 out of 30 who have reached the primary endpoint and continue to be alive and MFD-free at two years of follow-up.

There is no evidence of MFDs through nearly seven years (up to 82.7 months) of follow-up in the 27 patients who completed ALD-102.1

Fourteen patients in the long term study have reached at least their year five follow-up visit, including 7 patients who have reached at least their Year 6 follow-up visit.

The two patients from ALD-102 who have not reached month 24 have also shown no evidence of MFDs.

There was also interim data from the phase 3 study in patients with CALD after myeloablative conditioning using busulfan and fludarabine, a different chemotherapy conditioning regimen than that used in ALD-102 (busulfan and cyclophosphamide).

There is only safety data available so far due the limited follow-up duration of 8.6 months. So far there has been one serious adverse event on that trial.

The SAE was diagnosed in the presence of viral infection (adenovirus and rhinovirus/enterovirus positivity) approximately six months after eli-cel infusion and assessed as unrelated to eli-cel.

As of the data cut-off, the patient was partially responsive to steroids and plasmapheresis and was experiencing incontinence and ambulation issues.

  The post bluebird bio announces long-term data from CALD gene therapy appeared first on .

from https://pharmaphorum.com/news/bluebird-announced-long-term-data-from-cald-gene-therapy/

[max-clyde]

In a 2017 case report, a 13-year-old boy with SCD who had multiple vasoocclusive pain episodes and other SCD complications that were not improved with hydroxyurea or chronic transfusions was treated with an autologous hematopoietic cell transplant in which his own hematopoietic stem cells were transduced with this "anti-sickling variant" and returned to him after myeloablative chemotherapy. Following engraftment, he had increasing expression of the variant until it reached stable levels of approximately 50 percent of total hemoglobin at nine months, with a reciprocal decline in HbS expression. He became transfusion-independent, required no further analgesics, and had no vasoocclusive events during the post-transplant observation period of more than 15 months. There were no major adverse events other than the expected cytotoxicity of the conditioning regimen. Additional studies are underway to expand this approach to other individuals.

Abstract:

Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease.

[cancersfakianakis1]

Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: An analysis by the Acute Leukemia Working Party of the EBMT

Publication date: June 2018 Source:European Journal of Cancer, Volume 96 Author(s): Sebastian Giebel, Myriam Labopin, Michael Potter, Xavier Poiré, Henrik Sengeloev, Gerard Socié, Anne Huynh, Boris V. Afanasyev, Urs Schanz, Olle Ringden, Peter Kalhs, Dietrich W. Beelen, Antonio M. Campos, Tamás Masszi, Jonathan Canaani, Mohamad Mohty, Arnon Nagler BackgroundAllogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome–positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014.ResultsIn univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard ratio [HR], 1.5, P = 0.12) and URD-HSCT (HR, 1.6, P = 0.08) when referred to autoHSCT. The use of total body irradiation (TBI)–based regimens was associated with reduced risk of relapse (HR, 0.65, P = 0.02) and overall mortality (HR, 0.67, P = 0.01).ConclusionIn the era of TKIs, outcomes of myeloablative autoHSCT and alloHSCT for patients with Ph+ ALL in first molecular remission are comparable. Therefore, autoHSCT appears to be an attractive treatment option potentially allowing for circumvention of alloHSCT sequelae. Irrespective of the type of donor, TBI-based regimens should be considered the preferable type of conditioning for Ph+ ALL. https://ift.tt/2HSAETE

[itsmedicinesfakianakis]

Long-Term Survival After Hematopoietic Stem Cell Transplantation for Complete STAT1 Deficiency

Abstract

Purpose

Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT). Here, we describe the transplantation procedures and long-term outcomes.

Methods

The patient, who had suffered multiple life-threatening mycobacterial and viral infections in the first years of life, underwent HSCT at 4 years of age from a partially matched (HLA compatibility 8/10) unrelated donor after a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide, and anti-thymocyte globulin.

Results

Hematological reconstitution was detected at d+15, with full donor engraftment demonstrated by molecular analysis of leukocytes. Several complications occurred in the post-transplantation phase, including acute graft versus host disease, posterior reversible encephalopathy, thrombotic thrombocytopenic purpura, bilateral keratoconjunctivitis with complete loss of vision, and chronic lower limb lymphedema. Analysis of STAT1 in CD3+ cells at 90 and 120 days after HSCT by flow cytometry showed normal STAT1 phosphorylation levels in response to IFN-α.

Conclusions

Notably, no severe infections occurred after discharge (day + 90) during a 9-year follow-up, suggesting that normal response to IFNs in hematopoietic cells is sufficient to provide protection in humans.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2uIqM8t from OtoRhinoLaryngology - Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2fKIxNO

[healthcarebiz]

Neovii: Long-term Outcomes After Standard Graft-Versus-Host Disease (GvHD) Prophylaxis in Hemopoietic Cell Transplantation From Matched Unrelated Donors Strongly Support the Use of Grafalon® (Anti-Human-T-Lymphocyte Immunoglobulin) as Standard Therapy

RAPPERSWIL, Switzerland, June 26, 2017 /PRNewswire/ --

The 8-year follow-up results of a randomized phase 3 multicenter trial in adult patients with hematologic malignancies clearly showed more favorable results in the Grafalon® group

Severe GvHD-free and relapse-free survival was 34% in the Grafalon® group versus 13% in non-Grafalon® group

The probability of being alive and free of immunosuppressive therapy was 47% in Grafalon® group versus 11% in non-Grafalon® group

Relapse mortality was not increased by Grafalon®, supporting the long-term safety of Grafalon®

Neovii is pleased to announce the publication of the long-term outcomes of a multicenter parallel-group randomized trial conducted in Europe and Israel. The study looked at patients after standard GvHD prophylaxis with cyclosporine A and methotrexate with or without Grafalon® (anti-human-T-lymphocyte immunoglobulin- ATLG) (60 mg/kg total dose) in adult patients receiving myeloablative conditioning prior to hematopoietic stem cell transplantation from matched unrelated donors. Published in the June edition of The Lancet Haematology, the results showed the probability of being alive and free of immunosuppressive therapy at 8 years was 47% in the ATLG group and 11% in the non-ATLG[1] group.

"The significantly improved composite endpoint 'Severe GvHD free and relapse free survival' clearly indicates the impact of ATLG in the cure of patients without ongoing morbidity, which is the main aim of allogeneic stem cell transplantation. This is supported by the fact that the vast majority of patients alive after ATLG-containing GvHD prophylaxis are free of immunosuppressive therapy," said Professor Jürgen Finke, the principal investigator of the study and Deputy Head of the Department of Hematology and Oncology at the Faculty of Medicine and Medical Center at the University of Freiburg, Germany. Professor Finke is also Chairman of the German Stem Cell Transplant Working Group (DAG-KBT). He added, "The results clearly demonstrate the importance of ATLG administration in matched unrelated stem cell transplantation and will certainly influence decision-making and patient counselling in the long run."

Alexandre Sudarskis, CEO of Neovii, commented, "These ground-breaking results undoubtedly prove the long-term efficacy of Grafalon® administration as part of a myeloablative conditioning regimen." He added, "Neovii strives to better meet the needs of our patients and to improve their quality-of-life with our effective antibody therapies, allowing physicians to apply a safe and robust therapy." Neovii supports research and development activities in the fields of stem cell transplantation, solid organ transplantation, and immune and hemato-oncological disorders.

About the study  

Prospective, multicenter, open-label, randomized, phase 3 study of Grafalon® comparing standard ciclosporin A and methotrexate containing GvHD prophylaxis. Patients were randomized to either receive or not receive Grafalon®. The study was conducted in 9 European countries and Israel in 31 study centers, enrolling 202 patients. Patients had acute leukemia or myelodysplastic syndrome or myeloproliferative disease in an early (n=107) or advanced disease status (n=94). After myeloablative conditioning, patients received transplantation of blood stem cells (n=164) or bone marrow grafts (n=37). Study results were published in 2009[2] and 2011[3].

About GvHD  

Graft versus host disease (GvHD) is a serious, life threatening complication after allogeneic stem cell transplantation. It develops when the new immune system, which arises from the transplanted stem cells (graft), attacks tissues and organs of the recipient (host). It can be classified as acute or chronic, depending on the time of occurrence and/or the pathology.

About Grafalon®  

Grafalon® (formerly commercialized as ATG Fresenius), is a rabbit anti-human T-lymphocyte immunoglobulin, used as part of immunosuppressive regimens for the prevention of graft versus host disease in stem cell transplantation, prevention and treatment of rejection in solid organ transplantation or as immunosuppressive in the treatment of aplastic anemia (according to country-specific approved indications). With more than 200,000 treated patients to date in more than 50 countries, Grafalon® enjoys worldwide recognition among solid organ and stem cell transplant teams and has transformed the way transplant teams manage the care of their patients around the world.

About Neovii  

Neovii is an independent, dynamic and rapidly-growing global biopharmaceutical company with a patient-focused mission to develop and market novel life-transforming therapies. Neovii has been dedicated for over three decades to improving outcomes in transplantation medicine, hemato-oncological and immune disorders.

Neovii Pharmaceuticals AG global headquarters is in Rapperswil, Switzerland, with offices in Massachusetts, USA. Its biologics manufacturing facility is in Gräfelfing, Germany.

Neovii has a global reach with products sold in over 50 countries worldwide.

References 

[1] Finke, Jürgen et al. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. The Lancet Haematology, June 2017; 4(6):e293-e301.

[2] Finke, Jürgen et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncology, September 2009; 10(9):855-64.

[3] Socié, Gerard et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood, June 2011; 117(23):6375-82.

For further information

Contact info@neovii.com or call us at +41 55 210 05 00. For details on the full publication, visit http://ift.tt/wT4ua7.

  Read this news on PR Newswire Asia website: Neovii: Long-term Outcomes After Standard Graft-Versus-Host Disease (GvHD) Prophylaxis in Hemopoietic Cell Transplantation From Matched Unrelated Donors Strongly Support the Use of Grafalon® (Anti-Human-T-Lymphocyte Immunoglobulin) as Standard Therapy

[sicklecelledu-blog]

Transplant Versus Current Standard Care for Sickle Cell Disease

October 2016 - Presented by Sickle Cell 101

By Michael DeBaun, MD

The decision to perform a progenitor cell transplant (bone marrow transplant) for sickle cell disease has always been difficult for patients and parents. 

Transplantation has been considered an option in sickle cell disease because it is a potentially life threatening disease.  Historically, there have been few options for medical therapies capable of decreasing disease progression and providing a good quality of life.  Progenitor cell transplantation has traditionally used myeloablative conditioning (using chemotherapy to destroy the hematopoietic dividing cells in the bone marrow and throughout the body) and matched sibling donor (full brother or sister of the person with sickle cell disease).  Progenitor cell transplant has been the primary option to cure children with sickle cell disease; however, successful transplantation has been linked to long-term toxicities for some survivors, including but not limited to, severe chronic graft-versus-host disease and sterility.  The publication in 2015 of the multicenter, reduced-intensity, matched sibling donor transplantation trial conducted by Dr. Allison A. King and colleagues at eighteen centers around the world has provided critical information which advances our knowledge about progenitor cell transplant and its role for selected children with sickle cell disease and thalassemia.1

This study was conducted to determine whether progenitor cell transplantation using immunoablative (using medication that would decrease an immune response without completely eliminating all of the hematopoietic cells) reduced intensity therapy along with a matched sibling donor could be successful in curing sickle cell disease.  Over 12 years, a total of 43 children with SCD and nine with thalassemia received matched sibling donor transplantation with this reduced-intensity conditioning that included three drugs (alemtuzumab, fludarabine, and melphalan).  The overall (sickle cell and thalassemia) survival was 94.2 % and the event-free survival (no major adverse complications) 92.3 %, with a median follow-up of 3.42 years.  For sickle cell disease by itself, the survival was 93% and the event free survival was 90.7%.  After one year, no transplanted person was on immunosuppression and no graft versus host disease or rejection was noted.  For sickle cell disease, there were no new events (strokes, vaso-occlusive pain episodes, or pulmonary complications).

This study offers promise for children with sickle cell disease and a matched sibling donor to be able to receive immunoablative reduced-intensity transplantation.  Though this is encouraging the study falls short of becoming standard care for this population due to unanswered questions:

• The median follow-up of 3.4 years prevents the assessment of long-term complications, such as infertility, and the absence of the evaluation end-organ function dampens confidence about long term end-organ disease progression after transplant. • The biggest limitation is the lack of a comparison group of children with sickle cell disease receiving current medical therapy.  For children with sickle cell disease current advances in supportive therapy provide reasonable options to delay transplant until a clinical trial is completed comparing the short- and long-term complications of the transplant regimen to a comparable group of children receiving maximum medical therapy, the burden and progression of end organ damage may justify transplantation when compared to current therapy.

When this trial by Dr. King and colleagues started in 2003, hydroxyurea had not been recommended as standard care for children with SCD, but it is now recommended to offer hydroxyurea therapy at nine months.  In 2003, many hematologists elected to offer hydroxyurea therapy to those children with severe disease, with criteria similar to entry criteria for the transplant trial.

Recently two large pediatric sickle cell trials using current therapy have been completed.  In one prospective study, (prospective: children were enrolled, treated and followed over time), 185 children receiving hydroxyurea, with median duration of treatment of 10.3 years, had a 15 year survival of more than 98 percent.2 In the second retrospective study, (retrospective: medical records are reviewed for children on a therapy) 1,033 children with sickle cell disease were reviewed over an approximately 6.7 year period.3 They had a survival estimate over a five-year period of more than 98 percent.  These two large pediatric sickle cell disease studies provide inconvertible evidence that sickle cell disease in children is no longer a life threatening disease, but a chronic disease that may have life threatening episodes.

The multi-institutional reduced intensity conditioning and matched sibling transplant trial provides reasonable evidence for advancing the care of children with sickle cell disease.  However, the results fall short of recommending that this transplant strategy should become standard of care for sickle cell disease in children.

To advance the treatment of children with sickle cell disease, the next reduced-intensity conditioning transplant trial requires a longer follow-up duration, evaluation of end-organ disease, assessment of fertility, and a comparison group receiving maximum medical therapy.  Questions regarding the optimal reduced-intensity transplant for children with sickle cell disease deserve to be answered in a comparison study.  The work by Dr. King and colleagues brings us one step closer to finding that definitive answer.

1. King AA, Kamani N, Bunin N, et al. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol 2015;90:1093-8. 2. Le PQ, Gulbis B, Dedeken L, et al. Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment. Pediatr Blood Cancer 2015;62:1956-61. 3. Couque N, Girard D, Ducrocq R, et al. Improvement of medical care in a cohort of newborns with sickle-cell disease in North Paris: impact of national guidelines. Br J Haematol 2016;173:927-37. Abstracted from: Confirming a Reasonable for HSCT in Children with Hemoglobinopathies The Hematologist ASH News and Reports September-October 2016, Volume 13, Issue 5 Michael DeBaun, MD, MPH Professor of Pediatrics and Medicine, Director of the Vanderbilt-Meharry Center for Excellence in SCD Vanderbilt University Medical Center, Nashville, TN Published on: August 12, 2016

Published October 27, 2016

[tumimmtxpapers]

Fludarabine-based reduced toxicity yet myeloablative conditioning is effective and safe particularly in patients with high-risk thalassemia undergoing allogeneic transplantation.

Related Articles Fludarabine-based reduced toxicity yet myeloablative conditioning is effective and safe particularly in patients with high-risk thalassemia undergoing allogeneic transplantation. Pediatr Blood Cancer. 2018 Aug 01;:e27312 Authors: Sheth V, Grisariu S, Avni B, Stepensky P, Ashkenazi M, Shapira MY, Or R Abstract INTRODUCTION: Thalassemia major (TM) is an inherited disorder caused by ineffective erythropoiesis. At the present time, allogeneic stem cell transplantation (allo-SCT) is a curative option. Conventional busulfan and cyclophosphamide based myeloablative conditioning regimens are limited by increased toxicity, especially in high-risk patients. Replacement of cyclophosphamide with fludarabine has reduced toxicity and nonrelapse mortality (NRM), thus improving outcomes. We analyzed long-term data of our fludarabine-based myeloablative, reduced toxicity protocol, specifically in high-risk patients. METHODS: We retrospectively analyzed a cohort of 47 consecutive patients with TM undergoing allo-SCT from matched donors, using the fludarabine-based regimen (reduced toxicity regimen). The median age of the cohort was 10 years. Thirty-eight patients (80%) were in the high-risk and nine patients (20%) were in the low-risk category. The primary aim of this analysis was thalassemia-free survival (TFS). RESULTS: The rejection rate was 11% within high-risk patients with NRM of 2%. With a median follow-up period of 7 years (1-15 years), the 10-year TFS in the entire cohort was 87%, and the overall survival (OS) was 97%. The 10-year TFS and OS among the low-risk and high-risk groups were 90% versus 84%, respectively (P = 0.45) and 100% versus 96%, respectively (P = 0.5), and both subsets of patients did equally well. CONCLUSION: In conclusion, replacement of high-dose cyclophosphamide with fludarabine is well tolerated with minimal regimen-related toxicity and acceptable rejection rates, especially in high-risk patients. PMID: 30070020 [PubMed - as supplied by publisher] http://dlvr.it/Qdh4Gx

[adamupdates]

February 16, 2017- Emory Consultation

Adam met with Dr. Ned Waller, head of STEM Cell Transplantation at Emory’s Winship Cancer Institute.  The short of it is that he believes Adam’s best chance for a cure is another transplant. He agreed with Dr. Bashey that Adam’s leukemia would certainly come back if he only had chemotherapy and additional intrathecal chemo.  Asked what he would recommend if Adam were his patient, he said a haplo (half-match) transplant with me as the donor.  

He also recommended that the transplant take place as soon as possible, while Adam’s leukemia is still in remission.

According to Dr. Waller, there have been significant advances in haplo transplants and that the two places doing the most work in this field are Johns Hopkins, where the procedures were pioneered, and BMT at Northside Hospital. Because of Northside’s familiarity with Adam and Adam’s relationship with the doctors and staff, Dr. Waller recommended Adam stay with Northside.

During the meeting, Adam asked about his GVHD, particularly in his eyes, and how a transplant with a new donor might affect it. Unfortunately, Dr. Waller thought it would have little effect on his eyes and that dealing with the ocular GVHD may be something he will always have to deal with.

We also heard, for the first time, about dangers of intrathecal chemotherapy, including permanent nerve damage and paralysis.  We were told Dr. Bashey wanted to continue monthly intrathecal therapy through December 2017. At Adam’s BMT appointment today, his mid-level, Octavia, told him that they might be looking at only 6 more intrathecal treatments.  We don’t know if this change was a result of a phone conversation Dr. Bashey and Waller had after Adam’s Emory appointment, but we know that they did discuss the meeting.

So, Adam has decided to stay with BMT at Northside and go forward with the STEM cell transplant, with me as his donor.  Adam will meet with Dr Bashey on Monday and they will discuss the schedule and the pre-transplant conditioning regimen.  From what we understand, because this is a haplo transplant and Adam’s second transplant, the conditioning will not be myleoablative, designed to wipe out his immune system.  Rather it will be a reduced intensity conditioning where Adam receives less toxic chemo.  It’s designed to weaken his immune system to accept the transplant but not so strong  as to cause organ damage. Post transplant, additional chemotherapy will be used to reduce transplant rejection and GVHD.

We are all anxious about what happens next. Although more than two and a half years ago, the memories of Adam being very sick from the myeloablative conditioning, trips to the ER with fevers, seizure-like symptoms, weight and hair loss, and more time away from friends and family and Athens.

Adam is recovering well from his chemo. He did not need any blood products today and does not have to go back to the clinic until Monday, so a weekend off.  He is still neutropenic with levels about .3; he needs 1.0 to get back towards a normal range.

More after we get schedules next week.

[eurekamag--com]

Incidence of mixed chimaerism and clinical outcome in 101 patients after myeloablative conditioning regimens a

http://dlvr.it/NDHCRx