Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia

Jeng, Michael; Naidu, Paula; Rieman, Martha; Rodríguez‐Galindo, Carlos; Nottage, Kerri; Thornton, Donyell T.; Li, Chin‐Shang; Wiang, Winfred C.

doi:10.1002/pbc.20278

Cited by 16 publications

(12 citation statements)

References 34 publications

(20 reference statements)

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“…With the deep exploration of immune-mediated pathogenesis and accumulative clinical experience on IST, it has become the main method for the treatment of SAA when without matched haemopoietic stem cells. Its response rate could reach 60-80%, and the long-term survival rate and life quality of patients treated with IST could match those treated with BMT (Kojima et al 2000a, b;Goldenberg et al 2004;Führer et al 2005;Jeng et al 2005). The curative eVect of intensive IST for 14 SAA children from a total of 16 has been reported.…”

Section: Discussionmentioning

confidence: 92%

Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia

Chen

Hou

et al. 2012

J Cancer Res Clin Oncol

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Section: Discussionmentioning

confidence: 92%

Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia

Chen

Hou

et al. 2012

J Cancer Res Clin Oncol

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“…Of them, 19 trials were excluded for various reasons 3,7,[10][11][12]14,15,18,19,[22][23][24][25][26][27][28][29][30][31] (Figure 1). Six trials performed between 1991-2007 and randomizing 414 patients fulfilled inclusion criteria.…”

Section: Resultsmentioning

confidence: 99%

“…Design incompatible with inclusion criteria -13 trials 3,7,[10][11][12]14,15,18,[22][23][24][25][26] Randomization according to genetics: allo-HSCT vs. immunosuppressive therapy -1 trial 27…”

Section: Data Synthesis and Analysismentioning

confidence: 99%

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

Gurion¹,

Gafter‐Gvili²,

Paul³

et al. 2009

Haematologica

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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...

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“…Megadoses of methylprednisolone only added toxicities. Small pilots of GM-CSF 81 and much larger, randomized studies of G-CSF 71,82 as routine additions to ATG and cyclosporine have been negative to date; improved neutrophil counts did not translate into a higher rate of recovery or even less infection. A very large ongoing European study of G-CSF should definitively answer efficacy and safety concerns.…”

Section: Treatment Immunosuppressionmentioning

confidence: 99%

Current concepts in the pathophysiology and treatment of aplastic anemia

Young

Calado

Scheinberg

2006

Blood

773

529

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Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the ben- IntroductionMore than 25 years have passed since our first, highly speculative review of aplastic anemia; in that fortunately obscure publication, pathophysiology was addressed tentatively and immunosuppressive therapies hardly at all. The article did reflect both the dismal prospects for patients with the severe form of marrow failure and the formidable practical difficulties of experimentation in a rare disorder in which the cells of interest had disappeared. Aplastic anemia was considered heterogenous in origin and virtually impossible to study systematically. At the bedside, the clinical emphasis was the identification of a putative causal factorexposure to benzene or a culpable pharmaceutical-to allow classification in an otherwise doomed patient. As progenitor assays were developed, diverse factors could be held theoretically responsible for failure to form colonies in tissue culture, ranging from quantitative and qualitative defects in stem cells and blocks in differentiation to a lack of stroma support or inadequate cytokine production, or the effects of a chemical poison.In the intervening decades, our understanding of aplastic anemia has cohered around a unified immune mechanism of hematopoietic-cell destruction, which was inferred from but also has informed effective immunosuppressive therapies for the disease (Figure 1). Technical advances in cell biology, flow cytometry, molecular biology, and immunology have provided methods to measure numbers and function of very limited numbers of cells. As a result, we have a more unified and rational view of aplastic anemia's pathophysiology; the disease is understood in its relation to other related marrow failure syndromes; and in many important respects an unusual blood syndrome can model more common autoimmune diseases of other organ systems (Figure 2). Particularly satisfying is that aplastic anemia is now amenable to cure or amelioration in most patients, based both on high-quality clinical trials and mechanistic insights from the experiment...

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Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia

Cited by 16 publications

References 34 publications

Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia

Rabbit-antithymocyte globulin combined with cyclosporin A as a first-line therapy: improved, effective, and safe for children with acquired severe aplastic anemia

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

Current concepts in the pathophysiology and treatment of aplastic anemia

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