Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia

Chang, Myung Hee; Kim, Kyoung H.; Kim, Hyo S.; Jun, Hyun Jung; Kim, Dong H.; Jang, Jun Ho; Kım, Kihyun; Jung, Chul Won

doi:10.1111/j.1600-0609.2009.01378.x

Cited by 53 publications

(47 citation statements)

References 14 publications

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“…For example, in another recent study, higher ANC was also shown to be predictive of response. 30 Baseline ANC was also correlated with response in our study in univariable analysis, but was not seen to be an independent predictor in multivariable analysis once the impact of PNH clone and baseline ARC were taken into account (P=0.64).…”

Section: Discussionmentioning

confidence: 51%

“…Higher ALC and ARC were previously correlated with a higher survival rate 19 while in another study, only higher ARC was predictive. 30 As with response, distinct prognostic groups could be defined by using a simple scoring system to combine the effects of age and pretreatment ANC and ALC. The survival rate at 5 years for patients with two or fewer poor survival features was 71±9% compared to 16±10% for those with more than two poor survival features (P<0.001).…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Afable¹,

Shaik²,

Sugimoto³

et al. 2011

Haematologica

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BackgroundA combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Design and MethodsTwenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. ResultsResponse rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte globulin or horse anti-thymocyte globulin: 40% versus 55% (P=0.43), 45% versus 58% (P=0.44) and 50% versus 58% (P=0.61), respectively. No differences in early mortality rates or overall survival were observed. We then performed multivariable analyses of response at 6 months and overall survival and identified the presence of a paroxysmal nocturnal hemoglobinuria clone (P=0.01) and a pretreatment absolute reticulocyte count greater than 30¥10 9 /L (P=0.007) as independent predictors of response and younger age (P=0.003), higher pretreatment absolute neutrophil (P=0.02) and absolute lymphocyte counts (P=0.03) as independent predictors of overall survival. None of the immunogenetic polymorphisms studied was predictive of response to immunosupressive therapy. ConclusionsDespite reports suggesting differences in biological activity of different anti-thymocyte globulin preparations, rabbit and horse anti-thymocyte globulin appear to have a similar efficacy for upfront treatment of severe aplastic anemia. (Clinicaltrial.gov: NCT01231841)

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Afable¹,

Shaik²,

Sugimoto³

et al. 2011

Haematologica

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“…The utility of ARC in predicting IST outcomes has been confirmed in a proportion of reports, but not in others [12,[14][15][16][17]. Higher absolute neutrophil count (ANC) appears to be correlated with a better response rate of IST [15,18]; however, this result was not confirmed in Japanese and German children [12,19,20]. Further, the study of Japanese children demonstrated that lower white blood cell (WBC) count was indicative of a better response to IST rather than higher ANC [12].…”

Section: Pre-treatment Peripheral Blood Countsmentioning

confidence: 99%

“…When the two predictive parameters of ARC and ALC were combined, patients with higher baseline ANC and ARC had a response rate 40 % higher than those with lower baseline ANC and ARC (83 vs 41 %, p < 0.0001). The utility of ARC in predicting IST outcomes has been confirmed in a proportion of reports, but not in others [12,[14][15][16][17]. Higher absolute neutrophil count (ANC) appears to be correlated with a better response rate of IST [15,18]; however, this result was not confirmed in Japanese and German children [12,19,20].…”

Section: Pre-treatment Peripheral Blood Countsmentioning

confidence: 99%

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

Narita

Kojima

2016

Int J Hematol

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“…[17][18][19] No published series of patients with aplastic anemia has shown that rabbit-ATG is superior to horse-ATG in the context of first-line IST. [16][17][18][19][20][21][22] To date, there have only been a few reports on the efficacy of IST with rabbit-ATG in patients with MDS. 10,23,24 In this study, we compared the outcome of IST using horse-ATG with that of IST using rabbit-ATG in a large series of children with RCC.…”

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confidence: 99%

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Yoshimi

Heuvel‐Eibrink

Baumann³

et al. 2013

Haematologica

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Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090) Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood 16 In addition, a number of non-randomized studies showed inferior results for rabbit-ATG in adults and children with aplastic anemia. [17][18][19] No published series of patients with aplastic anemia has shown that rabbit-ATG is superior to horse-ATG in the context of first-line IST. [16][17][18][19][20][21][22] To date, there have only been a few reports on the efficacy of IST with rabbit-ATG in patients with MDS. 10,23,24 In this study, we compared the outcome of IST using horse-ATG with that of IST using rabbit-ATG in a large series of children with RCC. Methods Selection of patients for immunosuppressive therapyBone marrow and peripheral blood smears and bone marrow biopsies were centrally reviewed by reference pathologists in each country and the diagnosis of RCC was made according to the WHO criteria. 1,25 Fanconi anemia was excluded in all patients. Patients with RCC aged ≤18 years were enrolled in the prospective studies EWOG-MDS-98 (05/1998-12/2006) and EWOG-MDS-2006 (01/2007-08/2011. These studies were approved by the institutional review board of each participating institution. Written informed consent was provided by the patients' parents according to the Declaration of Helsinki.Patients with RCC are treated according to a risk-based strategy (Figure 1). Because of a high risk of disease progression, all patients with monosomy 7/7q-or three or more chromosomal aberrations undergo allogeneic hematopoietic stem cell transplantation (HSCT). 26 For patients without these unfavorable karyot...

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Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia

Abstract: Pre-IST neutrophil counts might predict the response to IST, while absolute ARCs prior to IST and response status after IST could be prognostic factors following IST.

Cited by 53 publications

References 14 publications

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

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