Revaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy.

Revaccination of pediatric HSCT recipients in accordance with this revaccination schedule provides a high level of protection against these vaccine-preventable diseases.

Summary:Graft failure, regimen-related toxicity and graft-versus-host disease (GVHD) are the critical barriers to unrelated donor transplants for aplastic anaemia (AA). We investigated the use of a novel conditioning regimen consisting of alemtuzumab (humanized CD52 antibody), fludarabine and cyclophosphamide in seven patients with AA, who underwent bone marrow transplant procedure using matched unrelated donors. The aetiology of AA was acquired (n ¼ 3), Fanconi's (n ¼ 3) and congenital (n ¼ 1). Median age was 13 years (range 8-35). All the donors were fully matched for HLA class I and II antigens using high-resolution typing. All the patients engrafted at a median of 18 days (range 13-35). Two patients died of transplant-related complications: one of adenovirus disease and the other developed extensive chronic GVHD of skin followed by cytomegalovirus (CMV) disease. Three patients developed Grade II acute GVHD disease (GVHD); none had Grade III-IV acute GVHD. Of the six evaluable patients, only one developed chronic GVHD. We conclude that this conditioning regimen for unrelated donor transplants for AA is sufficiently immunosuppressive to allow stable engraftment and appears to have a favourable impact on the incidence and severity of GVHD, warranting further investigation. The long-term survival of aplastic anaemia (AA) with bone marrow transplantation (BMT) using HLA-identical family donors has improved over the years and is in the range of 75-90%. 1-3 However, in comparison, the survival of patients transplanted from unrelated donors has only been in the range of 20-50%. 2,4-6 Main causes of transplantation failure in unrelated donor transplants in patients with AA (acquired as well as Fanconi's anaemia) are a high-incidence of graft failure, toxicities related to conditioning regimen and graftversus-host disease (GVHD). 5,6 To improve the outcome of unrelated donor transplants, a multidimensional approach using strategies addressing all the above issues is needed.The optimum conditioning regimen for unrelated donor transplants in AA is not known. Excellent long-term outcomes have been reported with cyclophosphamide (CY) and antithymocyte globulin (ATG) in the conditioning of acquired AA patients using HLA-identical family donors. 3 However, a similar approach with unrelated donors resulted in a high-incidence of graft failure. 7 Irradiation containing regimens result in better engraftment, but add substantial regimen-related toxicity and more GVHD resulting in no improvement in survival. [8][9][10][11] The role of low-dose total body irradiation (TBI, 200-300 cGy) in acquired AA has also been investigated and recommended as a measure to reduce graft rejection. 12,13 Even with low-dose of TBI, fatal pulmonary toxicity such as diffuse alveolar damage has been observed. 12 Alemtuzumab (Campath-1H) is a humanized IgG1 anti-CD52 monoclonal antibody (MoAb) and effectively depletes lymphocytes. In a pilot study, we previously reported a low incidence of GVHD in marrow transplants from HLA-identical sibling donors u...

Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.

Summary:Twenty-one paediatric patients (11 males and 10 females) received a CD34-selected partially matched related donor transplant for malignant (16 cases) and non-malignant conditions (five cases). The average cell dose was 11.13 ؋ 10 6 /kg. Fifteen of 16 patients with malignant conditions and one with non-malignant disease received total body irradiation plus cyclophosphamide. Three of 5 patients with non-malignant conditions and one with leukaemia, received busulphan plus cyclophosphamide. One patient with Fanconi anaemia received 100 mg/kg of cyclophosphamide. Fludarabine (25 mg/m 2 /day for 5 days) was administered prior to all these regimens. Additionally, anti-lymphocyte gamma-globulin (12.5 mg/kg/day) was administered from day ؊2 to day +2. Three (15%) patients failed to achieve complete chimaerism (CC). These patients received a second cell infusion. Two of them achieved CC. In the third patient, the percentage of donor cells was increased. The likelihood for engraftment was not related to the cell dose received. Acute graft-versus-host disease (GVHD) occurred in nine patients but only one developed GVHD Ͼgrade II. Eight patients developed active viral infections, which resolved after treatment. Patients receiving cell doses higher than our average had a significantly faster CD3 and CD4 cell recovery and experienced a lower incidence of viral infections. After 480 ؎ 255 days of median follow-up, 16/21 patients are alive and well and have CC. Three patients died of leukaemic relapse and a fourth from progression of his disease (adreno-leuko-dystrophy). We conclude that partially matched related donors are a feasible source of haemopoietic progenitor cells for transplantation for patients without matched familial or unrelated donors.

Strategies for reversing graft failure (GF) after allogeneic stem cell transplant (SCT) depend on the options available in each situation. GF was reported in 16 Spanish institutions from January 2006 to July 2011. Primary GF was defined as an absolute neutrophil count (ANC) > 0.5 × 10(9)/L not reached by day + 28 after SCT from peripheral blood (PB) or bone marrow (BM) progenitors and by day + 42 after SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a recurrent ANC < 0.5 × 10(9)/L. Eighty-nine patients with GF were reported, and 80 patients received a second SCT. The 5-year survival probability was 31% (95% confidence interval [CI]: 18-44%), and the incidences of non-relapse mortality and relapse estimated by competing risks were 47% (95% CI: 36-58%) and 21% (95% CI: 4-28%). The strategy adopted to treat GF was heterogeneous, and no approach could be unequivocally recommended for this situation. The prognosis of patients with GF was poor even after successful recovery from GF.

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Miconazole oral gel enhances acenocoumarol anticoagulant activity. Although we did not observe major bleeding complications, we suggest the use of other families of antifungal drugs, such as nystatin, to treat oral candidiasis in patients taking acenocoumarol.