Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient

Maury, Sébastien; Balère-Appert, Marie-Lorraine; Chir, Zina; Boiron, Jean Michel; Garrigue, Claire; Yakouben, Karima; Bordigoni, Pierre; Marie‐Cardine, Aude; Milpied, Noël; Kanold, Justyna; Maillard, Natacha; Socié, Gèrard

doi:10.3324/haematol.10899

Cited by 102 publications

(90 citation statements)

References 29 publications

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“…These figures are considerably lower when compared with most previous reports on allogeneic transplantation for AA. [15][16][17][18][19] Because of the small number of patients with GVHD, it is not possible to conclude from our study whether a high stem cell dose increases its risk. For haematological disorders in general, investigators have found a greater risk of chronic GVHD with PBSC transplant in the setting of a large CD34 þ cell dose.…”

Section: Discussionmentioning

confidence: 60%

“…15,16 Some researchers have considered the total mononuclear cell count as a variable with potential influence on graft failure and OS. 5,6,[17][18][19] Other published studies to date have not included CD34 þ cell dose in their analysis. [20][21][22][23][24] We used the median CD34 þ count to define the cutoff to ensure an even distribution of patients in the low-and high-dose arms.…”

Section: Discussionmentioning

confidence: 99%

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Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Islam

Anoop

Datta-Nemdharry

et al. 2009

Bone Marrow Transplant

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The precise effects of CD34 þ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34 þ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34 þ cell doses. Infusion of less than 2 Â 10 6 /kg of CD34 þ cells was associated with an increased incidence of graft failures (P ¼ 0.03), higher incidence of bacterial infections (P ¼ 0.006) and a delay in the engraftment of neutrophils (P ¼ 0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34 þ count. Other parameters, such as plt engraftment (P ¼ 0.63), red cell (P ¼ 0.94) and plt (P ¼ 0.31) transfusion independence, chimerism, acute and chronic GVHD (P ¼ 1.0) and OS (P ¼ 0.57), were not significantly influenced by the CD34 þ cell dose. These findings are different to the published studies on the relevance of CD34 þ cell dose in allogeneic transplantation for haematological cancers.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Islam

Anoop

Datta-Nemdharry

et al. 2009

Bone Marrow Transplant

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“…A median of 32 patients (range 11-349, total 1,645) were investigated in the total study population of 14 studies 11,[15][16][17][21][22][23][25][26][27][28][29]31,32 and in 8 relevant subgroups of 4 other studies. 10,20,24,30 The patients' median age in the individual studies was between eight and 27 years and the ratio of males : females ranged from a male (30 : 10) to a female preponderance (11 : 20).…”

Section: Patients' and Design Characteristicsmentioning

confidence: 99%

“…15,16,20,24 A consecutive enrolment was stated in 3 23,25,27 of 13 retrospective case series. 10,11,17,[21][22][23]25,[27][28][29][30][31][32] Transplantations were performed between 1981 and 2006.…”

Section: Patients' and Design Characteristicsmentioning

confidence: 99%

Decision-Making and Problem Solving

Saitis¹,

Saiti

2017

Initiation of Educators Into Educational Management Secrets

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Acquired severe aplastic anemia is a rare disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells from unrelated donors is a treatment option frequently offered to patients after failed immunosuppressive therapy. The aim was to investigate the outcome of these patients treated with unrelated donor transplants. Systematic literature searches were performed in MED-LINE, EMBASE, and The Cochrane Library. All databases were searched from inception to June 2009. Only full-text publications and studies including at least 10 patients were considered. The primary outcome was 5-year overall survival from the day of transplantation and the secondary outcomes were graft failure and graft-versus-host disease. A meta-analysis of survival estimates was conducted and heterogeneity was investigated. A total of 18 studies, one controlled trial and 17 case series were identified. The overall survival at five years and the corresponding confidence interval was stated in 8 studies and ranged from 28% to 94%. A meta-analysis revealed considerable heterogeneity between the studies that could not be explained and was also present in subgroups of the studies. The proportion of acute graft failure was 45% in one study using only umbilical cord blood, and it was reported to be 0-26% in 15 studies using mainly bone marrow as stem cell source after different follow-up periods. Acute GVHD grade II-IV was reported for 8-86% and extensive chronic GVHD for 0-38% of the evaluated patients in 16 studies. Recipient age, human leukocyte antigen match, performance status, year of transplantation, and conditioning with serotherapy were identified as significant factors for improved survival. Unrelated donor hematopoietic stem cell transplantation in patients with acquired severe aplastic anemia after failure to immunosuppressive therapy is a treatment option. A stable physical condition of the patients before receiving the transplant (for example, performance and age) may be associated with a better survival. Detailed HLA-matching facilitated by DNA-based typing, among other factors, may have contributed to recent improvements on survival after unrelated donor HSCT as a second-line treatment.Key words: donor stem cell transplantation, aplastic anemia, systematic review. Haematologica 2009. 94:1732-1742. doi:10.3324/haematol.2009 This is an open-access paper. ABSTRACT

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“…[1][2][3] However, recently, transplantation from unrelated donors has improved significantly because of better HLA matching, optimization of the conditioning regimen and improvement in supportive care. [4][5][6] For patients with inherited BMF or those with acquired BMF who fail IST and who lack a suitable alternative donor, the prognosis remains, however, extremely poor. Umbilical cord blood transplantation (UCBT) has extended the availability of hematopoietic SCT in the absence of a suitable donor.…”

mentioning

confidence: 99%

Cord blood transplantation in aplastic anemia

Latour

Rocha

Socié

2013

Bone Marrow Transplant

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For patients with inherited BM failure (BMF) or those with acquired BMF who fail immunosuppressive therapy and who lack a suitable alternative donor, the prognosis remains poor. Umbilical cord blood transplantation has extended the availability of hematopoietic stem cell transplantation in the absence of a suitable donor. A recent EBMT study confirmed the feasibility of this treatment and highlighted the fundamental role of the TNC dose (43.9 Â 10 7 /kg TNC/kg) on both engraftment and OS using cord blood as stem cell source in severe aplastic anemia. However, this procedure is still experimental and should be evaluated only through prospective clinical trials. (2013) 48, 201-202; doi:10.1038/bmt.2012.252; published online 7 January 2013 Bone Marrow TransplantationKeywords: cord blood; transplantation; aplastic anemia CORD BLOOD TRANSPLANTATION APLASTIC ANEMIA Acquired bone marrow failure (BMF) syndromes, such as severe aplastic anemia (SAA) or inherited Fanconi anemia, are rare diseases. The outcome of these patients has greatly improved over time, but is still poor for patients who lack a sibling donor and who failed or relapsed after immunosuppressive therapy (IST). Use of alternative donors has been historically associated with poor long-term survival. 1-3 However, recently, transplantation from unrelated donors has improved significantly because of better HLA matching, optimization of the conditioning regimen and improvement in supportive care. [4][5][6] For patients with inherited BMF or those with acquired BMF who fail IST and who lack a suitable alternative donor, the prognosis remains, however, extremely poor. Umbilical cord blood transplantation (UCBT) has extended the availability of hematopoietic SCT in the absence of a suitable donor. To date, double UCBT has been reported in only few patients with BMF.We evaluated this procedure in 14 patients (8 Fanconi anemia, 5 SAA and 1 paroxysmal nocturnal hemoglobinuria (PNH)) who received double cord blood transplantation (dUCBT) from 2004 to 2007 in Saint Louis Hospital in Paris, France. 7 With a median follow-up of 23 months, the estimated 2 year OS rates were 80±17% and 33±16% for patients with acquired and inherited BMF syndromes, respectively. Transplantation of two partially HLAmatched UCB thus enabled salvage treatment of high-risk patients with BMF syndromes. However, as dUCBT is associated with high incidence of GVHD, in spite of our limited experience, when possible, we have recommended the use of only one cord blood unit with high number of cells and not more than 1 out of 6 HLA mismatch in patients with Fanconi Anemia. 8 Results of single unit UCBT for patients with Fanconi anemia have been reported. OS was 40 ± 5% and factors associated with favorable outcome were use of fludarabine in the conditioning regimen, number of nucleated cells infused X4.9 Â 10 7 /kg, and negative CMV serology in the recipient. 2 Regarding results of UCBT in patients with acquired SAA, we have reported an analysis on 71 patients (33 males) diagnosed with SAA, (9 with PN...

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Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient

Cited by 102 publications

References 29 publications

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Decision-Making and Problem Solving

Cord blood transplantation in aplastic anemia

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