Transplantation for bone marrow failure: current issues

Latour, Régis Peffault de

doi:10.1182/asheducation-2016.1.90

Cited by 44 publications

(32 citation statements)

References 57 publications

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“…In the absence of a clinical trial, potential options include (in no particular order as reported outcomes are similar); Second course of IST, e.g. rabbit ATG following horse ATG failure (Scheinberg et al , ) Androgens (Chuhjo et al , ) Haploidentical or unrelated donor umbilical cord HSCT (Peffault de Latour et al , ; Clay et al , ; Peffault de Latour, ). Eltrombopag (Olnes et al , ) Alemtuzumab (Scheinberg et al , ) …”

Section: Patients Refractory To Ist With No Suitable Mud/mmud Availablementioning

confidence: 99%

Paediatric amendment to adult BSH Guidelines for aplastic anaemia

et al. 2017

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Section: Patients Refractory To Ist With No Suitable Mud/mmud Availablementioning

confidence: 99%

Paediatric amendment to adult BSH Guidelines for aplastic anaemia

et al. 2017

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“…The median time from the diagnosis of AA to the start of eltrombopag treatment was 7 months (IQR, 3-33). The patients received eltrombopag for a median of 5 months (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The median eltrombopag dose prescribed was 150 mg once a day, and CsA was associated with eltrombopag in two patients (18%) from this cohort.…”

Section: Eltrombopag Treatmentmentioning

confidence: 99%

“…Rapid front-line bone marrow transplantation with an HLAidentical sibling donor can lead to excellent outcomes. [1][2][3][4] However, most patients cannot undergo such a procedure because of the absence of a sibling donor or because of their age and/or co-morbidities. Immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine A (CsA) is considered to be the standard treatment in this situation, producing an overall hematologic response rate of 60-70%.…”

Section: Introductionmentioning

confidence: 99%

Nationwide Survey on the Use of Eltrombopag in Patients with Severe Aplastic Anemia: Report on Behalf of the French Reference Center for Aplastic Anemia

Lengliné

Drénou²,

Péterlin

et al. 2016

Blood

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BACKGROUND: Few therapeutic options are currently available for patients (pts) with severe aplastic anemia (SAA) refractory to antithymocyte globulin (ATG) plus ciclosporine (CsA) and not eligible for allogeneic stem cell transplantation. It has recently been reported that eltrombopag (ELT), a TPO receptor agonist, is efficient to improve tri-lineage blood counts in this setting. However, real-life use of this drug is still largely unknown. In pts with SAA refractory to ATG, physicians can accede to ELT in France through a compassionate use program. We took advantage of this program to assess the efficacy and safety of ELT in SAA pts. PATIENTS AND METHODS: The French National Reference Center for Aplastic Anemia conducted this study in pts who received ELT for the treatment of SAA. Latest guidelines were used to define disease severity, treatment indication, and response rates (Marsh et al, BJH 2014). The diagnosis of SAA was confirmed by marrow biopsy and Camita criteria for all pts. Pts were eligible if they received at least 2 months of ELT alone or in combination with other treatment in case of relapsed/refractory disease or front-line therapy for pts not eligible to the association of ATG and CsA. Pts were identified through a national e-mailing on behalf of the French reference center for SAA and the French Society of Hematology. All data presented here were collected at the reference date of June 26th, 2016. The study was conducted according to Helsinki's Declaration. RESULTS: Forty-six pts (male, 54%) who received ELT between July 2012 and February 2016 were identified in 17 French centers. Indications for ELT were relapsed/refractory SAA in 35 pts (76%) after 1 (49%), 2 (29%) or 3 (9%) courses of CsA+ATG. Eleven pts considered unfit for ATG also received the drug as first line therapy. The characteristics of the pts according to ELT indications are shown in Table 1. Median age at time of ELT initiation was 61 years [IQR 40 to 70]. 44 pts had idiopathic SAA including 17 (37%) with a detectable PNH clone (median size 7%). Two pts (4%) with dyskeratosis congenita also received ELT. ELT was introduced 17 months [8-50] after the initial diagnosis of SAA and with a median of 6 months [3-14] after the last course of immunosuppressive therapy. The maximal dose was 150 mg/day [100-150] for a median duration time of 6 months [4-12]. At last follow-up 22(48%) pts were still on treatment, 4(9%) pts stopped because of good hematological response, 1(2%) and 15(33%) after limited toxicity and failure to improve hematological status. Before treatment, median neutrophils count was 790/mm3 [500-1215] and pts received a median number of 4 red blood cells packs [2-4] and 3 platelets apheresis units [2-4] every month. Neutrophils counts were 765 [515-1475], 1100 [600-1800], 1200 [670-1915] and 1200/mm3 [757-2300] at 1, 3, 6 months and at last follow-up respectively. The rates of transfusion independence for both red cells and platelets were 7%, 33%, 46% and 46% at 1, 3, 6 months and at last follow-up. In pts achieving transfusion independence, hemoglobin and platelets level improved of 3 gr/dL [1.4, 4.5] and 42 G/L [11, 100], respectively. The rate of transfusion independence was not different among first line and refractory pts (p=0,5). We did not observe any response in the 2 patients with dyskeratosis congenita. No factor associated with hematological response to ELT was identified. Liver toxicity (cytolysis) occurred in 11 pts (1 grade 3 that required withdrawal of the treatment and 10 grade 1 who responded to dose reduction). 2 pts had a grade 2 intestinal toxicity which improved after dose reduction. Other side effects where related to SAA (28% infections, 13% hemorrhages). Bone marrow karyotype analysis after ELT was done in twelve pts (26%) (median time 14 months [5-22] after ELT start). In 10 pts the karyotype was normal, in one, trisomy 8 was identified (already seen at SAA diagnosis), and karyotype was a failure in 1 pt. CONCLUSION: We report here the first real-life multicenter study about the use of ELT in SAA. In a particular severe pts population with no other treatment possibility, we confirm a 40% rate of hematological improvement with transfusion independence. Some of the pts who were not eligible to ATG plus CsA (comorbidities) also received ELT first line with similar response rates. Elderly pts unfit for ATG may thus benefit from this treatment which at the best should be given through prospective clinical trials. Table 1 Table 1. Disclosures Ades: Celgene, Takeda, Novartis, Astex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terriou:Novartis: Consultancy; amgen: Consultancy. Peffault de Latour:Alexion: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

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“…Hence, HSCT provides a chance for radical PNH treatment. However, lethality and potential complications of the procedure are poorly predictable, and HSCT, therefore, cannot be recommended as a first-line strategy in the patients with classic PNH [6].…”

Section: Discussionmentioning

confidence: 99%

A mini-review on paroxysmal nocturnal hemoglobinuria and a case of Eculizumab treatment of PNH in elderly MDS patient

Дудина¹

2017

CTT

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SummaryParoxysmal nocturnal hemoglobinuria (PNH) is a systemic, acquired clonal hematological disorder which results from loss of complement-inhibiting proteins (CD55 and CD 59) from the blood cell surface. Therefore, such patients develop chronic complement-mediated intravascular hemolysis, with thromboses manifesting as most severe clinical complications. Recommendations of International PNH groups discern certain risk groups based on detection of a pathological cell clone, including patients with myelodysplastic syndrome (MDS). Here we describe detection of a clinically sound PNH clone in an elderly patient with MDS, as well as positive results of patho-genetic treatment with Eculizumab.

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Transplantation for bone marrow failure: current issues

Cited by 44 publications

References 57 publications

Paediatric amendment to adult BSH Guidelines for aplastic anaemia

Paediatric amendment to adult BSH Guidelines for aplastic anaemia

Nationwide Survey on the Use of Eltrombopag in Patients with Severe Aplastic Anemia: Report on Behalf of the French Reference Center for Aplastic Anemia

A mini-review on paroxysmal nocturnal hemoglobinuria and a case of Eculizumab treatment of PNH in elderly MDS patient

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