+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Long-term interleukin-3 and intensive immunosuppression in the treatment of aplastic anemia



Long-term interleukin-3 and intensive immunosuppression in the treatment of aplastic anemia



Cytokines and Molecular Therapy 2(4): 215-223



We have assessed in a phase I/II clinical study the tolerability and efficacy of long-term application of recombinant human interleukin-3 (rh-IL-3) in combination with antithymocyte globulin (ATG) and cyclosporin A (CSA) in 13 patients with aplastic anemia who were refractory to or relapsed after previous immunosuppressive treatment. Four cohorts of three patients were consecutively enrolled so that they received rh-IL-3 on days 9, 6, 3 and 1 after start of ATG/CSA treatment. Yeast-derived recombinant human IL-3 was administered by daily subcutaneous injection until day 90 at a dosage of 250 micrograms/m2. Long-term application of rh-IL-3 was well tolerated. The combination of rh-IL-3 with immunosuppression did not modify the known toxicities of ATG and CSA. Incidence and severity of rh-IL-3-related adverse events was less than in other phase I/II trials of rh-IL-3 as single-agent therapy. One might speculate that co-medication with CSA alleviates rh-IL-3-induced side effects. Three of eight patients with refractory AA and all four patients with relapsed AA responded to the combined treatment within four months. The median time to response was 91.5 days. There was evidence for an rh-IL-3-dependent response in two patients. Long-term rh-IL-3 did not cause stem cell exhaustion. One patient died early during the course of the study from EBV-driven lymphoproliferative disease. Two patients developed acute myeloid leukemia 4 and 22 months after cessation of rh-IL-3. In conclusion, long-term rh-IL-3 in combination with immunosuppression is well tolerated. The response rate to the combined treatment in refractory and relapsed AA was high. Recombinant human IL-3-dependent responses suggest efficacy. A prospective randomized trial comparing immunosuppression alone versus a combination with rh-IL-3 is warranted.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 046570401

Download citation: RISBibTeXText

PMID: 9384707


Related references

Long-term outcome in severe aplastic anemia is predicted by blood counts after treatment with intensive immunosuppression. Blood 98(11 Part 1): 749a, 2001

Long-term granulocyte-macrophage colony-stimulating factor and immunosuppression in the treatment of acquired severe aplastic anemia. Journal of Pediatric Hematology/Oncology 17(2): 140-144, 1995

Session on aplastic anemia 6. anti thymocyte globulin treatment in severe aplastic anemia long term follow up of 13 responder patients. Blut 41(3): 171-174, 1980

Long term follow up of severe aplastic anemia saa patients treated with immunosuppression is. Bone Marrow Transplantation 3(Suppl. 1): 239, 1988

Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood 85(11): 3058-3065, 1995

Phase I trials of interleukin-6 in patients with advanced renal cell carcinoma and patients with aplastic anemia Effects of long-term application and differences of hemopoietic response to IL-6 in patients with normal hemopoiesis versus patients with aplastic anemia. Blood 82(10 Suppl. 1): 368A, 1993

Intensive immunosuppression with antilymphocyte globulin , cyclosporine A and granulocyte-colony stimulating factor as treatment for acquired severe aplastic anemia. British Journal of Haematology 102(1): 305, 1998

Comparison of long-term outcome of children with severe aplastic anemia treated with immunosuppression versus bone marrow transplantation. Biology of Blood and Marrow Transplantation 3(1): 18-24, 1997

Marked improvement in short- and long-term survival in severe aplastic anemia patients treated with immunosuppression in the past 18 years. 2007

Intensive immunosuppression therapy for aplastic anemia associated with dyskeratosis congenita. International Journal of Hematology 83(3): 275-276, 2006

Intensive immunosuppression therapy for aplastic anemia associated with dyskeratosis congenita: report of a case. International Journal of Hematology 82(1): 35-37, 2005

Phase i ii trial of recombinant human interleukin 3 and immunosuppression in refractory or relapsed aplastic anemia. Experimental Hematology (Charlottesville) 20(6): 804, 1992

RAEB in T with monosomy 7 after treatment of severe aplastic anemia with long term G-CSF. Japanese Journal of Clinical Hematology 36(4): 365-370, 1995

Long-term danazol treatment for an adolescent girl with aplastic anemia. Asia-Oceania Journal of Obstetrics and Gynaecology 12(3): 365-370, 1986

Allogeneic marrow grafting for treatment of aplastic anemia: a follow-up on long-term survivors. Blood 48(4): 485-490, 1976