Natural history of moderate aplastic anemia in children

Howard, Scott C.; Naidu, Paula; Hu, X. Joan; Jeng, Michael; Rodríguez‐Galindo, Carlos; Rieman, Martha; Wang, Winfred C.

doi:10.1002/pbc.20131

Cited by 52 publications

(43 citation statements)

References 19 publications

(11 reference statements)

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“…When childhood non-severe AA is treated with supportive care, 67% of patients progress to develop severe AA, suggesting that it is important to consider early immunosuppressive therapy. 24 Our data indicate that immunosuppressive therapy is beneficial for some patients with non-severe AA. A previous Japanese study showed that the addition of G-CSF to immunosuppressive therapy increased the hematologic response rate after 6 months and reduced the relapse rate in adult patients with severe AA.…”

Section: Discussionmentioning

confidence: 62%

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

et al. 2011

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BackgroundAlthough the therapeutic outcome of acquired aplastic anemia has improved markedly with the introduction of immunosuppressive therapy using antithymocyte globulin and cyclosporine, a significant proportion of patients subsequently relapse and require second-line therapy. However, detailed analyses of relapses in aplastic anemia children are limited. Design and MethodsWe previously conducted two prospective multicenter trials of immunosuppressive therapy for children with aplastic anemia: AA-92 and AA-97, which began in 1992 and 1997, respectively. In this study, we assessed the relapse rate, risk factors for relapse, and the response to secondline treatment in children with aplastic anemia treated with antithymocyte globulin and cyclosporine. ResultsFrom 1992 to 2007, we treated 441 children with aplastic anemia with standard immunosuppressive therapy. Among the 264 patients who responded to immunosuppressive therapy, 42 (15.9%) relapsed. The cumulative incidence of relapse was 11.9% at 10 years. Multivariate analysis revealed that relapse risk was significantly associated with an immunosuppressive therapy regimen using danazol (relative risk, 3.15; P=0.001) and non-severe aplastic anemia (relative risk, 2.51; P=0.02). Seventeen relapsed patients received additional immunosuppressive therapy with antithymocyte globulin and cyclosporine. Eight patients responded within 6 months. Seven of nine non-responders to second immunosuppressive therapy received hematopoietic stem cell transplantation and five are alive. Eleven patients underwent hematopoietic stem cell transplantation directly and seven are alive. ConclusionsIn the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia. Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

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Section: Discussionmentioning

confidence: 62%

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

et al. 2011

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“…Clinically, the course of moderate aplastic anemia is variable: some patients progress to severe disease, others remain stable and may not require intervention; regular transfusions may not be required. 89 Very few clinical trials have specifically addressed moderate disease. Immunosuppression can reverse moderate pancytopenia and alleviate transfusion requirements; ATG and cyclosporine are more effective in combination, 73 but in practice are often used sequentially.…”

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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“…These patients may have moderate AA, a less severe form of AA that can persist for months or years, progress to more severe disease, or even resolve spontaneously. 5,30,31 As some cases of moderate AA 5,30,31 and lowgrade MDS (e.g., the 5qÀ syndrome 32,33 ) never progress to 34,35 whereas hypoplastic MDS patients generally have higher bone marrow CD34 þ cell counts. 9,10,36,37 However, significant overlap in the CD34 percentages between these two disorders has precluded using this assay diagnostically.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes

et al. 2006

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Natural history of moderate aplastic anemia in children

Abstract: When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

Cited by 52 publications

References 19 publications

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

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

Current concepts in the pathophysiology and treatment of aplastic anemia

Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes

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