Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation

Abstract

The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.

Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria

“…ATG response criteria. The ATG response criteria were adopted from those used for assessing a response in AA (Paquette et al, 1995). Patients were evaluated at 3 and 6 months following ATG for haematological response.…”

Disseminated colon cancer in a 15‐year‐old boy after immunosuppression for aplastic anemia

“…Recently, several studies have shown that long-term survivors of aplastic anemia are at high risk for solid tumors as well as clonal hematological complications, such as paroxysmal nocturnal haemoglobinuria, myelodysplastic syndrome or acute myelogenous leukemia. [1][2][3][4][5] Focusing on solid tumors as late complications after aplastic anemia treatment, there are many reports of solid tumors developing after stem cell transplantation. [2][3][4][5][6][7][8] However, the development of solid tumors after IST is rare.…”

“…[1][2][3][4][5] Focusing on solid tumors as late complications after aplastic anemia treatment, there are many reports of solid tumors developing after stem cell transplantation. [2][3][4][5][6][7][8] However, the development of solid tumors after IST is rare. The largest study from the European Group for Blood and Marrow Transplantation identified solid tumors in seven patients among 860 aplastic anemia patients treated with IST and in seven patients among 748 aplastic anemia patients treated with bone marrow transplantation (BMT).…”

“…1 Reported hematological response rates to IST are about 60% in SAA, however, patients are not considered cured because of the high rate of relapse and the development of clonal diseases. [1][2][3][4][5] Although an increased risk of solid tumors has also been observed after IST in aplastic anemia patients, 2-5 the development of colorectal cancer has not been reported, especially in children. Here, we report a case of disseminated colon cancer in a 15-year-old boy who received IST with antilymphocyte globulin (ALG), cyclosporine and methylprednisolone for SAA 10 years earlier.…”

Immunosuppressive therapy (IST) in adult patients with acquired aplastic anemia (AA): A single‐center experience over the past 15 years

“…6 With the improvement of (salvage) therapies in addition to supportive care measures, clinical outcomes in patients with AA have dramatically increased over the past four decades following IST or bone marrow transplantation (BMT) with an estimated 10-year survival rate of up to 80%. 7,8 Response rates (RRs) to IST vary according to different studies and the source of ATG. A hematologic recovery following front-line horse ATG-based IST (hATG) is seen in up to 60%-70% of patients, in comparison to 35%-45% in rabbit ATG (rATG)-treated patients with a significantly worse overall survival (OS), considering hATG as the first-line therapeutic option in AA.…”