Abstract:
:On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
journal_name
Bone Marrow Transplantjournal_title
Bone marrow transplantationauthors
Kansagra AJ,Frey NV,Bar M,Laetsch TW,Carpenter PA,Savani BN,Heslop HE,Bollard CM,Komanduri KV,Gastineau DA,Chabannon C,Perales MA,Hudecek M,Aljurf M,Andritsos L,Barrett JA,Bachanova V,Bonini C,Ghobadi A,Gill SI,Hidoi
10.1038/s41409-019-0451-2subject
Has Abstractpub_date
2019-11-01 00:00:00pages
1868-1880issue
11eissn
0268-3369issn
1476-5365pii
10.1038/s41409-019-0451-2journal_volume
54pub_type
杂志文章abstract::Bone marrow transplantation has been successfully employed in the treatment of Diamond-Blackfan anemia (DBA). Transplantation with bone marrow stem cells involves, however, considerable treatment-related toxicity, partially in the form of GVHD. Through the use of cord blood stem cells it may be possible to reduce the ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1700675
更新日期:1997-03-01 00:00:00
abstract::Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regime...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/s41409-018-0170-0
更新日期:2018-11-01 00:00:00
abstract::Localised Kaposi's sarcoma (KS) was diagnosed 240 days after allogeneic bone marrow transplantation (BMT) in a severely immunosuppressed HIV negative patient with genetic predisposition. The tumour was of host origin, based on PCR amplification of DNA minisatellites. Treatment with radiotherapy prompted almost complet...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Limited information is available regarding the incidence and features of lymphocyte expansions after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Large granular lymphocytes (LGL) expansions have been reported after bone marrow or peripheral blood, but not after unrelated cord blood (UCB) allo-HSCT, ...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/bmt.2016.364
更新日期:2017-06-01 00:00:00
abstract::Between December 1979 and February 1991, 89 patients with ALL received autologous BMT. Median patient age was 18.4 years. Ten patients were in first remission, 52 were in second or greater remission and 27 were in relapse at the time of transplant. Conditioning regimens utilized chemotherapy alone (5 patients) or in c...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::We report the experience of 14 centers which have used the combination of cytosine arabinoside (ara-C; 24-36 g/m2) and total body irradiation (TBI) to prepare 213 patients with acute lymphoblastic leukemia (ALL) for allogeneic BMT. The overall 3-year disease-free survival (DFS) probability is 38% (95% CI: 31-45%); 75 ...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1993-01-01 00:00:00
abstract::Acute hemorrhagic cystitis due to adenovirus infections may be more severe or protracted in immunocompromised patients. This patient with chronic graft-versus-host disease following allogeneic marrow transplantation for acute myelogenous leukemia developed painful hematuria due to adenovirus infection that failed to r...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::The role of amifostine in the prevention of cyclophosphamide-induced hemorrhagic cystitis (HC) was evaluated in the rat model. Urinary bladders from control rats that received no drugs (group I) were compared with those from rats receiving cyclophosphamide alone at a dose of 150 mg/kg (group II), and two other groups ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1701598
更新日期:1999-03-01 00:00:00
abstract::Cord blood (CB) is used increasingly in transplant patients lacking sibling or unrelated donors. A major hurdle in the use of CB is its low cell dose, which is largely responsible for an elevated risk of graft failure and a significantly delayed neutrophil and platelet engraftment. As a positive correlation has been s...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/bmt.2009.289
更新日期:2010-06-01 00:00:00
abstract::New concepts of allogeneic hematopoietic SCT (allo-HSCT) for neuroblastoma and other solid tumors do not rely on escalation of chemotherapy intensity and tumor load reduction but rather on a graft-vs-tumor effect. At this point, this is still an investigational and unusual application of allogeneic transplant, with 78...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/bmt.2008.279
更新日期:2008-10-01 00:00:00
abstract::The pathogenesis of acute graft-versus-host disease (aGVHD) includes tumor necrosis factor-alpha (TNFalpha) expression by macrophages and T cells. However, the temporal comparison of donor vs host cells to TNFalpha expression in response to irradiation conditioning and alloreactivity has not been reported. This study ...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704362
更新日期:2004-02-01 00:00:00
abstract::To evaluate the incidence and risk factors for secondary solid tumors in Japan after allogeneic hematopoietic SCT (allo-HSCT), 2062 patients who had received allo-HSCT between 1984 and 2005 were retrospectively analyzed. Twenty-eight patients who developed 30 solid tumors were identified a median of 5.6 years after tr...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,多中心研究
doi:10.1038/bmt.2011.23
更新日期:2012-01-01 00:00:00
abstract::Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few d...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1702743
更新日期:2001-01-01 00:00:00
abstract::Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primar...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704663
更新日期:2004-12-01 00:00:00
abstract::The purpose of this study was to measure the trajectory of psychosocial recovery over the first year after bone marrow transplantation (BMT). BMT patients were assessed at baseline (n = 86), hospital discharge (n = 74), 100 days (n = 64) and at 1 year (n = 45). Participants completed the Functional Assessment of Cance...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bmt.1701115
更新日期:1998-03-01 00:00:00
abstract::We describe two patients who developed respiratory syncytial virus (RSV) pneumonia after BMT. One died of RSV pneumonia after three courses of steroid pulse therapy. Surprisingly, RSV antigen was identified in the bronchoalveolar lavage fluid (BALF) obtained post mortem. Steroid pulse therapy might have suppressed ant...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1702559
更新日期:2000-09-01 00:00:00
abstract::A 5-year-old girl with Ph-positive chronic myelogenous leukemia, who underwent umbilical cord blood transplantation, developed two episodes of electrical status epilepticus while receiving tacrolimus (FK506) then cyclosporin A (CsA), as treatment against graft-versus-host disease. MRI including diffusion weighted MR i...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704168
更新日期:2003-09-01 00:00:00
abstract::Fludarabine is a purine analog that has demonstrated significant activity in B-cell malignancies, including CLL. Fludarabine also possesses an immunosuppressive effect and is being used to prevent GVHD in hematopoietic stem cell transplantation. However, the molecular mechanism by which fludarabine inhibits immunoreac...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1705901
更新日期:2008-02-01 00:00:00
abstract::Hematopoietic stem cell transplantation (HSCT) for autoimmune diseases have been, because of safety reasons, overwhelmingly autologous. Results are, in general, encouraging with improvement in quality of life, a remission of up to several years, and perhaps in some diseases improved survival. This indicates that furth...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/sj.bmt.1703950
更新日期:2003-08-01 00:00:00
abstract::Graft-versus-tumour reactions as a form of adoptive immunotherapy may help prevent the recurrence of haematological malignancy following allogeneic BMT. We hypothesised that such reactions may be maximised by shortening the duration of post-transplant immunosuppression by a rapid taper of cyclosporine (CYA). CYA dose ...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bmt.1700961
更新日期:1997-11-01 00:00:00
abstract::Intermediate-dose salvage therapy is frequently given for relapsed and resistant lymphomas and is usually intensely myelosuppressive. In an attempt to reduce the haematological toxicity of miniBEAM, one of the commonly used salvage regimens, peripheral blood stem cell (PBSC) support was given to 21 consecutive patient...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Relapse rates in patients after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) continue to be high despite the use of aggressive conditioning regimens. Based on studies in the murine system a clinical protocol was developed that utilizes immunotherapy to obtain a graft-versus-leukemia (G...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophi...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Four human fetuses were treated by transplantation of human fetal liver stem cells. Two of them had severe immunodeficiency disease and the two other ones had thalassemia major. Three of these in utero transplants were followed by engraftment. The three patients are now born: the first one is now very healthy thanks t...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matche...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1704172
更新日期:2003-09-01 00:00:00
abstract::In the original version of this article, the mention of 'ifosfamide 1500 mg/m2 days 1-3' should, in fact, read 'ifosfamide 1500 mg/m2 bd days 1-3'. This has now been updated in the original version of the article. ...
journal_title:Bone marrow transplantation
pub_type: 已发布勘误
doi:10.1038/s41409-019-0504-6
更新日期:2020-04-01 00:00:00
abstract::In a series of 74 patients with hematological malignancies undergoing allogeneic bone marrow or peri- pheral blood stem cell transplants from an HLA-identical sibling donor, four developed diffuse alveolar hemorrhage (DAH) between days 0 and 23 post transplant. Diagnosis was made by the radiographic finding of diffuse...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/sj.bmt.1701995
更新日期:1999-10-01 00:00:00
abstract::Sixty-nine adolescents and adults 15-51 years of age with untreated acute lymphoblastic leukaemia (ALL, 54 patients) or lymphoblastic lymphoma (LL, 15 patients) were referred for intensive antileukaemic therapy. Patients were treated according to one of two protocols. Both included induction and consolidation with vin...
journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::HLA-identical sibling donor transplantation remains the treatment of choice for Wiskott-Aldrich Syndrome (WAS). Since 1990, utilization of alternative donor sources has increased significantly. We report the hematopoietic cell transplantation (HCT) outcomes of 47 patients with WAS treated at a single center since 1990...
journal_title:Bone marrow transplantation
pub_type: 杂志文章
doi:10.1038/bmt.2012.31
更新日期:2012-11-01 00:00:00
abstract::Hematopoietic SCT is currently the only curative therapy for a range of benign inherited and acquired primary hematologic disorders in children, including BM failure syndromes and hemoglobinopathies. The preferred HLA-matched sibling donor is available for only about 25% of such children. However, there has been subst...
journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
doi:10.1038/bmt.2015.1
更新日期:2015-05-01 00:00:00