Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia

Kekre, Natasha; Zhang, Ying; Zhang, Mei Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H. Joachim; Kapoor, Neena; Lee, Jong Wook; Nakamura, Ryotaro; Pulsipher, Michael A.; Eapen, Mary; Antin, Joseph H.

doi:10.3324/haematol.2017.164459

Cited by 42 publications

(46 citation statements)

References 25 publications

(24 reference statements)

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“…23 This was based on higher rates of acute and chronic GvHD when using horse ATG compared with rabbit ATG. 23 This was based on higher rates of acute and chronic GvHD when using horse ATG compared with rabbit ATG.…”

Section: Discussionmentioning

confidence: 99%

Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party

et al. 2018

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We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.

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Section: Discussionmentioning

confidence: 99%

Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party

et al. 2018

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“…To reduce toxicity in older patients, newer regimens have incorporated fludarabine with lower-dose cyclophosphamide and with ATG (FCA) or alemtuzumab (FCC), with improved OS [37–39]. A CIBMTR analysis of 833 AA bone marrow transplants evaluated the role of ATG source on transplant outcomes, and demonstrated that rabbit ATG (Thymoglobulin, Sanofi, France) results in lower rates of acute and chronic GVHD for MSD transplants, improves survival, and lowers rates of acute GVHD for MUD transplants [40]. Conditioning for MUD and haploidentical transplants also includes 200 cGy total body irradiation [41].…”

Section: Transplant-based Therapies For Saa/vsaamentioning

confidence: 99%

Diagnosis and Treatment of Aplastic Anemia

Peslak

Olson

Babushok

2017

Curr. Treat. Options in Oncol.

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Opinion Statement Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with upfront closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long term clonal complications.

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“…However, several questions remain open, the first being whether we should continue to use ATG in 2017, especially as a prospective trial in 134 SAA patients failed to show a benefit for patients randomized to the horse ATG arm. 7 The study by Kekre and et al 1 focused solely on patients receiving ATG, and thus we are missing the control arm. A registry-based study on HLAidentical sibling transplants (n=1886) showed a significant survival advantage for patients receiving ATG , irrespective of whether this was derived from horse or rabbit, both in univariate and multivariate analysis.…”

mentioning

confidence: 99%

“…Unfortunately, we do not have prospective studies comparing these two important variables, and the study by Kekre et al 1 could not address this issue because the dose of ATG was not captured in the database. A conventional dose for thymoglobulin in transplants for SAA is between 5 and 7.5 mg/kg (total dose), administered in the 3 days before transplant; for ATGAM this would convert to a total dose of 120 mg/kg.…”

mentioning

confidence: 99%

“…We now have evidence that rabbit ATG (thymoglobulin) seems to protect patients from GvHD, better than horse ATG. The study by Kekre et al 1 did not include patients receiving rabbit ATG-fresenius, so we do not have a comparison of this ATG with thymoglobulin and ATGAM. Another T cell depleting agent is alemtuzumab, which has been shown to achieve the same, if not superior protection against acute and chronic GvHD when compared to thymoglobulin in the transplant setting of SAA;…”

mentioning

confidence: 99%

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