Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Gluckman, Éliane; Cappelli, Barbara; Bernaudin, Françoise; Labopin, Myriam; Volt, Fernanda; Carreras, Jeanette; Simões, Belinda Pinto; Ferster, Alina; Dupont, Sophie; Fuente, Josu de la; Dalle, Jean‐Hugues; Zecca, Marco; Walters, Mark C.; Krishnamurti, Lakshmanan; Bhatia, Monica; Leung, Wing; Yanik, Gregory A.; Kurtzberg, Joanne; Dhédin, Nathalie; Kuentz, Mathieu; Gautier, Michel; Apperley, Jane F.; Lutz, Patrick; Neven, Bénédicte; Bertrand, Yves; Vannier, Jean Pierre; Ayas, Mouhab; Cavazzana, Marina; Matthes‐Martin, Susanne; Rocha, Vanderson; Elayoubi, Hanadi; Kenzey, Chantal; Bader, Peter; Locatelli, Franco; Ruggeri, Annalisa; Eapen, Mary

doi:10.1182/blood-2016-10-745711

Cited by 390 publications

(407 citation statements)

References 50 publications

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“…The goal of BMT is to seed the bone marrow with new normal bone marrow that will begin to produce normal, non-sickling RBCs indefinitely. [6] BMT cures SCD in greater than 90% of cases although there are serious risks associated with the procedure. [6] Moreover, less than 20% of the SCD patient population hasappropriately matched sibling donors available [6] and thus are eligible for BMT.…”

Section: Introductionmentioning

confidence: 99%

“…[6] BMT cures SCD in greater than 90% of cases although there are serious risks associated with the procedure. [6] Moreover, less than 20% of the SCD patient population hasappropriately matched sibling donors available [6] and thus are eligible for BMT. Although BMT with non-sibling donors is being investigated, it has more immunological side effects, higher mortality rates and it will be several years before this treatment is readily available to patients.…”

Section: Introductionmentioning

confidence: 99%

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Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease

et al. 2017

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Introduction: Sickle cell disease (SCD) is a chronic genetic disease with high morbidity and early mortality; affecting nearly 100,000 individuals in the United States. Bone marrow transplantation, the only curative treatment, is available to less than 20% of patients, due to a number of access barriers. Gene transfer therapy (GTT) has shown to be curative in animal models, and is approved for use in humans for early-phase studies at a few centers. GTT would offer a more accessible treatment option available to all patients. It is important to understand patient perspectives on GTT to help ensure human clinical trial success. Methods: Two focus groups were conducted with younger (18–30 years) and older (≥ 31 years) adults with SCD to obtain data on patient knowledge and beliefs about GTT. Data from these two focus groups was used to develop a GTT educational brochure. A third focus group was conducted to obtain participant feedback on acceptability and feasibility of education and the brochure. Results: Most adults, especially young adults, had little knowledge about GTT and expressed fear and uncertainty about the side effects of chemotherapy (e.g., hair loss, infertility), use of a human immunodeficiency virus (HIV)-derived viral vector, and potential for cancer risk. Participants wanted full transparency in educational materials, but advised researchers not to share the vector’s relation to HIV due to cultural stigma and no HIVvirus is used for the GTT-vector. Conclusions: Older adults had more desire to participate in human clinical GTT trials than younger participants. When recruiting for trials, researchers should develop GTT educational materials that address participant lack of trust in the healthcare system, cultural beliefs, fears related to side effects, and include visual illustrations. Use of such materials will provide adults with SCD the information they need to fully evaluate GTT.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease

et al. 2017

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“…However, the potential morbidity and mortality associated with HSCT, insignificant overall survival and disease free-survival when compared to patients treated symptomatically, coupled with high cost of HSCT, have led to its underuse [107]. A recent international survey done by Gluckman et al reported excellent long-term survival in patients with HLA (Human leukocyte antigen)-identical sibling transplantation [7], but lack of healthy HLA-matched siblings makes it a significant challenge. However, the evolution of partially myeloablative conditioning regimens and haploidentical HSCT may allow more widespread use of this modality in the near future and increase the donor pool [108].…”

Section: Other Strategiesmentioning

confidence: 99%

“…Despite the known nature of the disease, progress in the science and the overall management has been a relatively slow process. The recent advent of new therapeutic targets [4,5], use of gene therapy [6], and excellent success rate of HLA-identical sibling transplantation [7] have brought new hope to the scientific and affected communities.…”

Section: Introductionmentioning

confidence: 99%

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

Ansari

Moufarrej

Pawliński

et al. 2017

Expert Review of Hematology

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Introduction Sickle cell disease (SCD) is a devastating monogenic disorder that presents as a multisystem illness and affects approximately 100,000 individuals in the United States alone. SCD management largely focuses on primary prevention, symptomatic treatment and targeting of hemoglobin polymerization and red blood cell sickling. Areas covered This review will discuss the progress of SCD over the last few decades, highlighting some of the clinical (mainly cerebrovascular) and psychosocial challenges of SCD in the United States. In addition, focus will also be made on the evolving science and management of this inherited disease. Expert Commentary Until recently hydroxyurea (HU) has been the only FDA approved therapy for SCD. However, advancing understanding of SCD pathophysiology has led to multiple clinical trials targeting SCD related thrombo-inflammation, abnormal endothelial biology, increased oxidant stress and sickle cell mutation. Yet, despite advancing understanding, available therapies are limited. SCD also imposes great psychosocial challenges for the individual and the affected community, which has previously been under-recognized. This has created a pressing need for complementary adjuvant therapies with repurposed and novel drugs, in addition to the establishment of comprehensive clinics focusing on both the medical treatment and the psychosocial issues associated with SCD.

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“…9,10 More recently, a promising, but still experimental, approach based on gene and cellular therapy methods has been proposed aiming to correct the sickle gene defect in the patient’s own stem cells. 21,22 …”

Section: Introductionmentioning

confidence: 99%

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

Rafii

Bernaudin

Rouard³

et al. 2017

Haematologica

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Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had a previous child diagnosed with homozygous sickle cell disease. Participation was voluntary and free of charge. All mothers underwent mandatory serological screening. Cord blood units were collected in different hospitals, but processed and stored in two public banks. A total of 338 units were stored for 302 families. Median recipient age was six years (11 months-15 years). Median collected volume and total nucleated cell count were 91 mL (range 23–230) and 8.6×108 (range 0.7–75×108), respectively. Microbial contamination was observed in 3.5% (n=12), positive hepatitis B serology in 25% (n=84), and homozygous sickle cell disease in 11% (n=37) of the collections. Forty-four units were HLA-identical to the intended recipient, and 28 units were released for transplantation either alone (n=23) or in combination with the bone marrow from the same donor (n=5), reflecting a utilization rate of 8%. Engraftment rate was 96% with 100% survival. Family cord blood banking yields good quality units for sibling transplantation. More comprehensive banking based on close collaboration among banks, clinical and transplant teams is recommended to optimize the use of these units.

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Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Cited by 390 publications

References 50 publications

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease

Sickle cell disease: a malady beyond a hemoglobin defect in cerebrovascular disease

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks

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