scholarly journals Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2540-2546 ◽  
Author(s):  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
A Baruchel ◽  
M Boogaerts ◽  
J Briere ◽  
...  
Keyword(s):  
Partial Response ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Bone Marrow Failure ◽  
Randomized Study ◽  
Alternative Therapy ◽  
Survival Rates ◽  
Severe Aplastic Anemia ◽  
Actuarial Survival ◽  
Significant Difference

Abstract We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

scholarly journals Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2540-2546 ◽  
Author(s):  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
A Baruchel ◽  
M Boogaerts ◽  
J Briere ◽  
...  
Keyword(s):  
Partial Response ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Bone Marrow Failure ◽  
Randomized Study ◽  
Alternative Therapy ◽  
Survival Rates ◽  
Severe Aplastic Anemia ◽  
Actuarial Survival ◽  
Significant Difference

We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

scholarly journals A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1861-1869
Author(s):  
N Young ◽  
P Griffith ◽  
E Brittain ◽  
G Elfenbein ◽  
F Gardner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Bone Marrow Failure ◽  
Multicenter Trial ◽  
Severe Aplastic Anemia ◽  
Transfusion Independence ◽  
Group I ◽  
Significant Difference ◽  
To Receive

One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

scholarly journals A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1861-1869 ◽  
Author(s):  
N Young ◽  
P Griffith ◽  
E Brittain ◽  
G Elfenbein ◽  
F Gardner ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Bone Marrow Failure ◽  
Multicenter Trial ◽  
Severe Aplastic Anemia ◽  
Transfusion Independence ◽  
Group I ◽  
Significant Difference ◽  
To Receive

Abstract One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

A multicenter randomized study comparing cyclosporin-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia

1992 ◽  
Vol 5 ◽  
pp. 271-275 ◽  
Author(s):  
Eliane Gluckman ◽  
Hélène Esperou-Bourdeau ◽  
André Baruchel ◽  
Michel Boogaerts ◽  
Jean Briere ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Randomized Study ◽  
Severe Aplastic Anemia

scholarly journals Intensive Immunosupressive Therapy Combining with Eltrombopag for Adult Chinese Patients with Severe Aplastic Anemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2190-2190
Author(s):  
Ruixin Li ◽  
Yuanyuan Jin ◽  
Jinsong Jia ◽  
Shengyun Lin ◽  
Yan Yang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Regression Model ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
T Cell Subsets ◽  
Phase Iii ◽  
Chinese Patients ◽  
Severe Aplastic Anemia ◽  
Significant Difference

Abstract In sight of different pharmacokinetics between races, the recommended dose is 75mg/d for Asian using eltrombopag [1]. However, the efficacy and safety of antithymocyte immunoglobulin (ATG) and cyclosporin A (CsA) with eltrombopag are still largely unknown for adult Asian patients with severe aplastic anemia (SAA). From May 2014 to March 2021, 121 Chinese adult patients with SAA were treated with IST (r-ATG, 3.5mg/kg/d × 5d and CsA 3-5 mg/kg/d) or in conjunction with eltrombopag (75mg/d, from day 1 to 6 months) prospectively and non-randomly. The adverse events (≥3 grades) referring to Common Terminology Criteria for Adverse Events version (CTCAE) 5.0 within 6 months. In pretreatment evaluation of clinical and laboratory characteristics. Median age (39 years and 40 years) was comparable. The complete blood count with differential and quantification of CD4/CD8 T-cell subsets were similar in both groups, but median time from diagnosis to treatment (16 d and 28 d, P=0.038) was different significantly (Table 1). The Chi-Squared test was used to compare the efficacy. The overall response rates (ORR) of IST alone or in combination with eltrombopag in the 1st, 3rd, 6th and 12th month after IST were 12% vs 35% (P=0.002), 44% vs 64% (P=0.028), 61% vs 85% (P=0.006) and 73% vs 91% (P=0.031), respectively. The complete response (CR) rates in the 3rd, 6th and 12th month after IST are 7% vs 17% (P=0.069), 14% vs 27% (P=0.11) and 33% vs 32% (P=0.92) (Table 2). We analyzed factors associated with the efficacy at 6 months by the Binary-Logistic regression model. Elements would be listed in multivariate analysis whether the factors might impact on the efficacy or had P value lower than 0.2 in univariate analysis. It was suggested that ORR was significantly related with the use of eltrombopag (P=0.011, OR=3.600, 95%CI 1.345-9.638) (Table 3). The overall survival (OS) and factors related to survival were analyzed by Kaplan-Meier method and Cox regression model. The OS in IST combined with eltrombopag group was 98% compared to 88% for IST alone (P=0.078). No significant intergroup differences were noted in multivariate analysis of OS. The nonhematologic adverse events (≥3 grades) were infrequent, occurring in 16% patients. 8 in IST plus E-PAG cohort and 11 in IST alone cohort (15% vs 16%, P=0.80). Hepatic injury was prevalent complication (6% vs 8%, P=0.96), relatively. But none showed significant difference between two groups. Discussion It has been reported that eltropopag promoted the response of megakaryocytic or even three lineages in refractory SAA [2]. The 6th month CR rate and ORR of our study are lower than the results of Townsley's research with 35% and 94% in the cohort of IST plus eltrombopag [1]. But the CR rate ORR is comparable to De Latour's results with 21.9% and 59.4% in the 3rd month [3]. Median age and dosage of eltrombopag needs to be considered with caution between different researchs, whist the efficacy of horse ATG (hATG) and rATG remained a subject of some debate [4]. Townsley et al. had reported that hepatic impairment (≥3 grades) was 18% [1], but our research showed lower rate of liver impairment with 6%. We should increase the sample volume to analyze the adverse events. Reference [1] Townsley DM, et al. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia [J]. N Engl J Med, 2017, 376 (16): 1540-1550. [2] Desmond R, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug [J]. Blood, 2014, 123 (12): 1818-1825. [3] De Latour, RP, et al. Results of the EBMT SAAWP Phase III Prospective Randomized Multicenter RACE Study of Horse ATG and Ciclosporin with or without Eltrombopag in naive SAA patients. EBMT 2020 abstract O018. [4] Vallejo, C., et al., Rabbit antithymocyte globulin versus horse antithymocyte globulin for treatment of acquired aplastic anemia: a retrospective analysis. Annals of Hematology, 2015. 94(6): p. 947-954. Figure 1 Figure 1. Disclosures He: F. Hoffmann-La Roche Ltd.: Consultancy; LongBio Pharma: Consultancy, Research Funding.

scholarly journals Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 184-188 ◽  
Author(s):  
RE Champlin ◽  
WG Ho ◽  
SA Feig ◽  
DJ Winston ◽  
C Lenarsky ◽  
...  
Keyword(s):  
Placebo Group ◽  
Confidence Interval ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Response Rates ◽  
Severe Aplastic Anemia ◽  
Actuarial Survival ◽  
The Difference ◽  
To Receive ◽  
Historical Controls

We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.

scholarly journals Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 184-188 ◽  
Author(s):  
RE Champlin ◽  
WG Ho ◽  
SA Feig ◽  
DJ Winston ◽  
C Lenarsky ◽  
...  
Keyword(s):  
Placebo Group ◽  
Confidence Interval ◽  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Response Rates ◽  
Severe Aplastic Anemia ◽  
Actuarial Survival ◽  
The Difference ◽  
To Receive ◽  
Historical Controls

Abstract We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.

scholarly journals Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3058-3065 ◽  
Author(s):  
SJ Rosenfeld ◽  
J Kimball ◽  
D Vining ◽  
NS Young
Keyword(s):  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Severe Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Current Treatment ◽  
Subsequent Treatment ◽  
Severe Aplastic Anemia ◽  
Therapeutic Trial ◽  
Allogeneic Bone ◽  
Actuarial Survival

Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia.

scholarly journals Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with or without sirolimus: a prospective randomized study

Haematologica ◽  
2009 ◽  
Vol 94 (3) ◽  
pp. 348-354 ◽  
Author(s):  
P. Scheinberg ◽  
C. O. Wu ◽  
O. Nunez ◽  
P. Scheinberg ◽  
C. Boss ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Randomized Study ◽  
Severe Aplastic Anemia ◽  
Prospective Randomized Study

scholarly journals Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 119-125 ◽  
Author(s):  
R Storb ◽  
HJ Deeg ◽  
V Farewell ◽  
K Doney ◽  
F Appelbaum ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Study Groups ◽  
Severe Aplastic Anemia ◽  
High Dose ◽  
Actuarial Survival ◽  
Host Disease ◽  
Improvement In Survival

Forty-six patients with severe aplastic anemia (median age, 23 years) were treated with high-dose cyclophosphamide followed by infusion of marrow from an HLA-identical family member. To evaluate postgrafting prophylaxis for graft-v-host disease (GVHD), they were entered into a prospective randomized trial comparing the effect of a combination of methotrexate and cyclosporine (n = 22) to that of methotrexate alone (n = 24). Forty-four of the forty-six patients had evidence of sustained marrow engraftment. Only one patient in each of the two study groups showed graft rejection. A significant reduction in the cumulative incidence of grades II to IV acute GVHD was seen in patients given methotrexate/cyclosporine (18%) compared with those given methotrexate alone (53%) (P = .012). In three patients given methotrexate alone, grade III developed, and in six, grade IV acute GVHD developed, compared with none given methotrexate/cyclosporine. Eighteen of the 22 patients given methotrexate/cyclosporine and 15 of the 24 given methotrexate alone are alive between 5.5 and 44.5 months (median, 18 months), with actuarial survival rates at 2 years of 82% and 60%, respectively (P = .062). The incidence of fatal infections was higher in patients given methotrexate alone, whereas there are as yet no significant differences in the incidence of chronic GVHD. We conclude that methotrexate/cyclosporine treatment resulted in a significant decrease in the incidence and severity of acute GVHD in patients who received transplants for severe aplastic anemia and thus an improvement in survival.

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