High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Abstract

Severe aplastic anemia (SAA) is a lifethreatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatmentnaive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for severe aplastic anemia. Large randomized controlled trials will be necessary to establish how results of high-dose cyclophosphamide compare with either bone marrow transplantation or standard immunosuppressive regimens, such as antithymocyte globulin and cyclosporine. (Blood. 2010;

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

“…1 Some might argue that treatment success in selected cases of syngeneic transplant is, in fact, not due to the transplant but is only the result of the immunosuppressive conditioning and posttransplant immunosuppression; as we know, treatment of AA with high-dose cyclophosphamide has been a topic of debate in the past. 17,18 Though the inability to measure donor chimerism precludes proof of syngeneic engraftment, rapid neutrophil recovery, as well as lack of influence of ATG, are strong surrogate indicators of actual engraftment rather than response to immunosuppressive treatment, which usually occurs after several months. 3 Despite the widespread use of ATG, its role in pre-transplant conditioning is also not clear in the setting of matched sibling transplant, where a randomized study failed to confirm the positive effect on engraftment observed in a retrospective comparison.…”

Unexpected unrelated umbilical cord blood stem cell engraft in two patients with severe aplastic anemia that received immunosuppressive treatment: A case report and literature review

“…Hematological responses to transfusion independence appear in ~2/3 of patients; however, disease relapse ultimately occurs in 30-40% of patients (1,4). A 10-year follow-up study revealed that the response rate of SAA is 71% and the actual event-free survival is 58% in 44 treatment-naïve patients with SAA that received high-dose cyclophosphamide (15). The success of IST application is significantly limited by poor response, high relapse and clonal evolution.…”

The optimal immunosuppressive therapy for aplastic anemia

“…After this promising pilot study, a phase 3 prospective trial to compare response rates to IST with either high-dose CY/CsA or ATG/CsA in treatment-naïve patients with SAA was conducted, which is terminated prematurely because of excessive early mortality related to fatal infectious complications followed by delayed neutrophil recovery of the CY/CsA arm [41]. However, a recently published long-term follow-up report of 67 SAA patients (44 treatment-naïve and 23 refractory) who were treated with high-dose CY (50 mg/kg for 4 consecutive days) showed acceptable response rates of 70.5 % (including CR of 43.2 %) and 47.8 % (including CR of 21.7 %), while the actual OS at 10 years was 88 and 61.8 % in treatment-naïve and refractory patients, respectively [46]. Early mortality rate was acceptable (7.5 %), but the cumulative incidence of fungal infections in the early post-treatment period at 2 months was 21 % in treatment-naïve and 39 % in refractory patients.…”

“…A third course of ATG-containing IST showed benefit only in previous responders, but not in patients who were refractory to previous IST [40]. On the other hand, cyclophosphamide (CY) or alemtuzumab is used as alternative IST regimen in these patients [41][42][43][44][45][46].…”