Updated Guidelines for the Treatment of Acquired Aplastic Anemia in Children.

PURPOSE OF REVIEW: This review aimed to provide updated guidelines for the management of children with acquired aplastic anemia (AA), particularly focusing on hematopoietic stem cell transplantation (HSCT). RECENT FINDINGS: Failure-free survival for children with aplastic anemia has been shown to be better after bone marrow transplantation (BMT) from matched or one-locus mismatched related donors (MRD/1MMRD) than after immunosuppressive therapy (IST). A combination of the absence of minor paroxysmal nocturnal hemoglobinuria clones and short telomere length was identified as a strong predictor of a poor response to IST. Upfront HSCT from matched unrelated donors (MUD) and MRD was recently demonstrated to have comparable outcomes. Moreover, unrelated cord blood transplantation (UCBT) and haploidentical HSCT have shown promising outcomes, and the fludarabine/melphalan-based regimen has resulted in excellent survival without poor graft function. BMT from MRD/1MMRD is the treatment of choice. When a MRD/1MMRD is not available, upfront BMT from a MUD should be considered for patients with only a slim chance of responding to IST. UCBT and haploidentical HSCT are promising options. This updated treatment algorithm should improve overall outcomes for children with AA.

The Suppressive Effect of Quercetin on Toll-Like Receptor 7-Mediated Activation in Alveolar Macrophages.

Respiratory viral infections that cause chronic airway and lung disease can result in the activation of the innate immune response. Alveolar macrophages (AMs), one of the first lines of defense in the lung, are abundantly located in alveoli and the respiratory tract. Flavonoids found in fruits and vegetables exhibit cytoprotective effects on various cell types. In this study, we investigated the effect of quercetin on activation of AMs that had been exposed to imiquimod, a ligand of Toll-like receptor (TLR) 7. In both a mouse AM cell line (AMJ2-C11 cells) and mouse bronchoalveolar fluid cells, we demonstrated that quercetin attenuated TLR7-induced the expression of TNF-α and IL-6. In AMJ2-C11 cells, quercetin also attenuated the TLR7-induced CD40 expression; attenuated the translocation of p65; induced translocation of Nrf2 from cytosol to nucleus; and induced heme oxygenase (HO)-1 expression. Notably, tin protoporphyrin IX (SnPP), an inhibitor of HO-1, also attenuated TLR7-induced transcription of the TNF-α and IL-6 genes, suggesting that the effect of quercetin is mediated by HO-1. These results suggest that dietary supplementation with quercetin may have efficacy in the treatment of respiratory viral infection.

Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT.

Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes.

Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan.

Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia.

We conducted a prospective multicenter study to compare the efficacy of repeated immunosuppressive therapy (IST) with stem-cell transplantation (SCT) from an alternative donor in children with acquired aplastic anemia (AA) who failed to respond to an initial course of IST. Patients with severe (n = 86) and very severe disease (n = 119) received initial IST consisting of antithymocyte globulin (ATG) and cyclosporine. Sixty patients failed to respond to IST after 6 months from the initial IST and were eligible for second-line treatment. Among them, 21 patients lacking suitable donors received a second course of IST. Three patients developed an anaphylactoid reaction to ATG and could not complete the second IST. A trilineage response was seen in only 2 of 18 (11%) evaluable patients after 6 months. Thirty-one patients received SCT from an alternative donor. At 5 years from the initiation of second-line therapy, the estimated failure-free survival (FFS), defined as survival with response, was 83.9% (+/- 16.1%, SD) in the SCT group compared with 9.5% (+/- 9.0%) in the IST group (P = .001). These results suggest that SCT from an alternative donor offers a better chance of FFS than a second IST in patients not responding to an initial IST.