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 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 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 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.

A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation

Blood ◽  
2011 ◽  
Vol 117 (17) ◽  
pp. 4434-4441 ◽  
Author(s):  
André Tichelli ◽  
Hubert Schrezenmeier ◽  
Gérard Socié ◽  
Judith Marsh ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Antithymocyte Globulin ◽  
Randomized Study ◽  
Working Party ◽  
Severe Aplastic Anemia ◽  
Controlled Study ◽  
Newly Diagnosed ◽  
Entire Cohort ◽  
Post Hoc ◽  
To Receive

Abstract We evaluated the role of granulocyte colony-stimulating factor (G-CSF) in patients with severe aplastic anemia (SAA) treated with antithymocyte globulin (ATG) and cyclosporine (CSA). Between January 2002 and July 2008, 192 patients with newly diagnosed SAA not eligible for transplantation were entered into this multicenter, randomized study to receive ATG/CSA with or without G-CSF. Overall survival (OS) at 6 years was 76% ± 4%, and event-free survival (EFS) was 42% ± 4%. No difference in OS/EFS was seen between patients randomly assigned to receive or not to receive G-CSF, neither for the entire cohort nor in subgroups stratified by age and disease severity. Patients treated with G-CSF had fewer infectious episodes (24%) and hospitalization days (82%) compared with patients without G-CSF (36%; P = .006; 87%; P = .0003). In a post hoc analysis of patients receiving G-CSF, the lack of a neutrophil response by day 30 was associated with significantly lower response rate (56% vs 81%; P = .048) and survival (65% vs 87%; P = .031). G-CSF added to standard ATG and CSA reduces the rate of early infectious episodes and days of hospitalization in very SAA patients and might allow early identification of nonresponders but has no effect on OS, EFS, remission, relapse rates, and mortality. This study was registered at www.clinicaltrials.gov as NCT01163942.

Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 1756-1761 ◽  
Author(s):  
Masanao Teramura ◽  
Akiro Kimura ◽  
Satsuki Iwase ◽  
Yuji Yonemura ◽  
Shinji Nakao ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Aplastic Anemia ◽  
Immunosuppressive Therapy ◽  
Antithymocyte Globulin ◽  
Randomized Study ◽  
Severe Aplastic Anemia ◽  
Febrile Episodes ◽  
To Receive

Abstract We report the results of a randomized study to elucidate whether addition of granulocyte colony-stimulating factor (G-CSF) to immunosuppressive therapy is valuable for the treatment of severe aplastic anemia (SAA) in adults. A total of 101 previously untreated patients (median age, 54 years; range, 19 to 75 years) were randomized to receive antithymocyte globulin (ATG) and cyclosporin A (CyA) (G-CSF− group) or ATG, CyA, and G-CSF (G-CSF+ group). In the G-CSF+ group, the hematologic response rate at 6 months was higher (77% vs 57%; P = .03) than in the G-CSF− group. No differences were observed between the groups in terms of the incidence of infections and febrile episodes. There were no differences between the G-CSF− group and the G-CSF+ group in terms of survival (88% vs 94% at 4 years), and the development of myelodysplastic syndrome (MDS)/acute leukemia (AL) (1 patient vs 2 patients). However, the relapse rate was lower in the G-CSF+ group compared with the G-CSF− group (42% vs 15% at 4 years; P = .01). Further follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy for adult SAA.

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.

Sign in / Sign up

Export Citation Format

Share Document