Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis

Abstract

Immunosuppressive therapy is the treatment for aplastic anemia patients ineligible for transplantation. The role of hematopoietic growth factors as adjunct to treatment in these patients is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials comparing treatment with immunosuppressive therapy and hematopoietic growth factors to immunosuppressive therapy alone in patients with aplastic anemia. Two reviewers appraised the quality of trials and extracted data. For each trial, results were expressed as relative risks with 95% confidence intervals (CI) for dichotomous data. The addition of hematopoietic growth factors yielded no difference in overall mortality at 100 days, one year and five years [relative risks 1.33 (95% CI 0.56-3.18), relative risks 0.90 (95% CI 0.50-1.63) and relative risks 0.89 (95% CI 0.55-1.46), respectively]. There was no difference in overall hematologic response and in the occurrence of infections. HGF significantly decreased the risk for relapse, relative risks 0.45 (95% CI 0.30-0.68, 3 trials). Hematopoietic growth factors were not associated with higher occurrence of myelodysplastic syndrome and acute myeloid leukemia or paroxysmal nocturnal hemoglobinuria. The addition of hematopoietic growth factors does not affect mortality, response rate or infections occurrence. Therefore, it should not be recommended routinely as an adjunct to the immunosuppressive therapy for patients with aplastic anemia.Key words: hematopoietic growth factors, aplastic anemia, immunosuppressive therapy. Gafter-Gvili A, Paul M, Vidal L, Ben-Bassat I, Yeshurun M, Shpilberg O, and Raanani P. Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy systematic review and meta-analysis. Haematologica 2009; 94:712-719. doi:10.3324/haematol.2008.002170 ©2009 Ferrata Storti Foundation. This is an open-access paper. Citation: Gurion R, ABSTRACT Hematopoietic growth factors in aplastic anemia patients treated with immunosuppressive therapy-systematic review and meta-analysis © F e r r a t a S t o r t i F o u n d a t i o nclusive regarding their effect on hematologic response and the incidence of infections. Most of them could not show a survival benefit. 4,[14][15][16][17] Furthermore, secondary clonal disorders, mainly clonal evolution to myelodysplastic syndrome (MDS) or to acute myelogenous leukemia (AML) were of concern in some of the trials. 11,18,19 We undertook this systematic review and meta-analysis in order to assess the role of the addition of HGF to IST in aplastic anemia, mainly severe aplastic anemia, and specifically to evaluate their effect on mortality, overall hematologic response and on the occurrence of MDS/AML and paroxysmal nocturnal hemoglobinuria (PNH). Design and Methods Data sources and searchesWe searched PubMed (January 1966 20 We scanned the references of all included studies and reviews identified for additional trials that did not come up in our search. Study selectionWe included all randomized, controlled t...

Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

“…The addition of hematopoietic growth factors did not affect mortality, response rate, or occurrence of infections, but did significantly decrease the risk of relapse. 26 The data from our AA-92 trial were included in this meta-analysis. In contrast to the other five studies in the meta-analysis, only our study included patients with non-severe AA, who had a significantly higher relapse rate than that of patients with either severe AA or very severe AA.…”

Supportive care in severe and very severe aplastic anemia

“…35,36 There are currently no data to support the routine use of growth factors in AA either alone are as adjunct to immunosuppression. 1,31,32 NEUTROPENIC FEVER Fever with neutropenia is an indication for immediate hospitalization. Diagnostic procedures should include careful physical examination, blood cultures and cultures from other relevant sites, while chest X-ray is optional but often useful.…”

“…[30][31][32][33] The addition of G-CSF to triple immunosuppression with ATG, ciclosporin and cortcosteroids accelerates the recovery of neutrophils und reduces the rate of early infections and the length of hospital stay. 4,34 Addition of G-CSF does not improve trilineage response, EFS, relapse rate and OS.…”

Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia

“…[7][8][9][10] Previous studies of cytokines in aplastic anemia have not shown a benefit, probably because hematopoietic stem and progenitor cells do not have receptors for erythropoietin or G-CSF. 21 Thrombopoietin levels are significantly elevated in patients with aplastic anemia, in contrast to thrombopoietin levels in patients with immune thrombocytopenic purpura, which are at the high end of the normal range. 20 Eltrombopag does not compete with thrombopoietin for binding to c-MPL, since it binds in the membrane-spanning region outside the ligand-binding pocket of c-MPL, and it activates signaling through JAK-STAT (Janus-associated kinase-signal transducers and activators of transcription) and MAPK (mitogen-activated protein kinase) pathways.…”