Safety and efficacy of targeted busulfan therapy in children undergoing myeloablative matched sibling donor BMT for sickle cell disease.

Busulfan influences engraftment and toxicities during hematopoietic stem cell transplantation (HSCT). We report our single-institution experience of targeted busulfan therapy for myeloablative, matched sibling donor (MSD) HSCT for sickle cell disease (SCD) and assess the relationships of busulfan levels to engraftment and toxicities. Twenty-seven patients with SCD underwent MSD HSCT from 1993 to 2007, 25 with busulfan measurements. The conditioning regimen was busulfan (initial dose 0.875 mg/kg for 16 doses), CY and antithymocyte globulin. Busulfan area under curve (AUC) was determined with the first dose, and dose adjustments were made to target the desired AUC range. Median AUC was 963 µmol min/L (range 780-1305 µmol min/L). Engraftment occurred in all cases: 21 (84%) full donor chimerism (> 95% donor cells), 4 (16%) partial donor chimerism. Hepatic veno-occlusive disease (VOD) occurred in 8 (32%) patients. Lower AUC was seen with partial donor chimerism (862 ± 73 µmol min/L) versus full donor chimerism (AUC 1018 ± 122 µmol min/L) (P = 0.022). VOD was not associated with busulfan AUC (P = 0.153). Of 25 patients, 24 survived with median follow-up of 4.9 years. Our experience shows that targeting busulfan AUC above the range used in previous multicenter trials appears safe and may contribute to sustained engraftment in SCD.

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Humoral response to vaccination with interleukin-2-expressing allogeneic neuroblastoma cells after primary therapy.

BACKGROUND: Immunotherapy using cytokine-expressing tumor cells has shown promise as an anticancer strategy. We have recently begun a trial of interleukin-2 (IL-2) gene-modified allogeneic neuroblastoma cells administered in a sequence of eight injections to patients with high-risk neuroblastoma following completion of primary therapy. Six patients to date have completed treatment. PROCEDURE: We examined humoral responses to the immunizing cell line and, when available, to the patients' autologous tumor cells using an in vitro binding assay. RESULTS: Five of six patients developed a rise in antitumor antibodies to the immunizing neuroblastoma cell line following vaccination. Two of these patients had autologous tumor available; both demonstrated a humoral response to these cells as well. CONCLUSIONS: Our results demonstrate that vaccination with IL-2-expressing allogeneic tumor cells after intensive primary therapy can elicit a humoral response to the immunizing line. These antibodies are cross-reactive with the patients' own tumor cells in the two cases in which autologous cells were available. This suggests that different patients' tumors may share common antigens that can be exploited in immunotherapy strategies and supports the continued exploration of allogeneic tumor cells as tumor vaccines.

Budd-Chiari syndrome caused by Gaucher's disease.

We present a unique case of Budd-Chiari syndrome caused by Gaucher's disease. The diagnosis was based on Doppler sonography, magnetic resonance imaging, contrast-enhanced three-dimensional magnetic resonance angiography, standard venography, and venous pressure measurements and was confirmed histologically.