Elevated pretransplant ferritin is associated with a lower incidence of chronic graft-versus-host disease and inferior survival after myeloablative allogeneic haematopoietic stem cell transplantation.

Elevated pretransplant serum ferritin levels have been associated with an increased incidence of morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HCT). We studied 222 patients who underwent myeloablative allogeneic HCT in whom pretransplantation serum ferritin levels were available. Pretransplantation ferritin > 1910 microg/l was associated with lower overall survival (P = 0.003), lower relapse-free survival (P = 0.003), decreased chronic graft-versus-host disease (GVHD) (P = 0.019) and increased non-relapse mortality (NRM) (P = 0.042). Similar results were obtained when pretransplantation ferritin was analysed as a continuous variable and by quartiles. Our results indicate that an elevated pretransplant ferritin level adversely impacts transplantation outcomes. The adverse impact of elevated ferritin on NRM and survival was despite its association with lower incidences of acute and chronic GVHD, which are major causes of NRM. The association of ferritin with iron overload and its influence on HCT outcomes requires further prospective validation.

Elevated ferritin is associated with relapse after autologous hematopoietic stem cell transplantation for lymphoma.

Elevated serum ferritin is associated with reduced survival following allogeneic transplantation and an increased risk of toxic and infectious complications after autologous hematopoietic stem cell transplantation (ASCT). We studied 315 patients who underwent ASCT for Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at our institution in whom pretransplantation ferritin was available to determine its association with survival. On multivariate analysis, a pretransplantation ferritin>685 ng/mL was associated with significantly lower overall (OS; P=.002) and relapse-free survival (RFS; P=.021). Ferritin>685 ng/mL was associated with a higher incidence of relapse (P=.005) and relapse mortality (P<.001), but not of nonrelapse mortality (NRM; P=.23). Similar results were seen when pretransplantation ferritin was analyzed as a continuous variable and by quartiles. Our results indicate the need for studies designed to correlate an elevated ferritin with iron overload and to analyze the benefit of strategies to reduce the extent of iron overload.

Fluorescence in situ hybridization (FISH) as primary methodology for the assessment of HER2 Status in adenocarcinoma of the breast: a single institution experience.

The demand for both reflexed and primary fluorescence in-situ hybridization (FISH) testing in the clinical setting is increasing. Relevant literature has reported the incidence of HER2 overexpression in 20% to 30% of cases, but some reports suggest that HER2 gene amplification rates are substantially lower. Published data, however, on primary FISH assessment from a single institution is limited, especially information about the frequency of the anomalous genotypes defined by FISH. We report our experience with primary FISH testing in 742 consecutive cases of breast cancer, in the calendar year 2006. Eighty percent (595/742) of the breast cancer cases were not amplified for HER2 (HER2/CEP17=0.8-1.9), whereas 19% (142/742) of cases were HER2 amplified (HER2/CEP17>or=2.0). Among the HER2-amplified cases, 3% (19/742) were low-level amplified (HER2/CEP17 ratio=2.0-2.5). Genotypic heterogeneity, defined as >5% but <50% of the tumor cells demonstrating HER2 gene amplification, was observed in 5% (40/7242) of the cases. HER2 monoallelic deletion (HER2/CEP1780% of tumor cells) was observed in 2% (13/742). Polysomy, if defined as CEP17 spot count 3.0 or more in at least 80% of tumor cells, was observed in 3% (20/742) of the cases. These data may be helpful as benchmarks for other institutions initiating primary FISH analysis for HER2 genotyping.

High-dose busulfan and the risk of pulmonary mortality after autologous stem cell transplant.

The non-relapse mortality of autologous stem cell transplant is low enough that the procedure has been extended to older patients with non-Hodgkin's lymphoma. We treated 537 non-Hodgkin's lymphoma patients with high-dose chemotherapy consisting of busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. Sixteen patients were identified who died of pulmonary complications at a five-year incidence of 3.6%. Risk factors for pulmonary mortality included older age and lower baseline D(CO) and FEV1. We conclude that high-dose busulfan is associated with pulmonary mortality after autologous transplant, particularly in older patients.

Timed sequential chemotherapy with concomitant granulocyte colony-stimulating factor for high-risk acute myelogenous leukemia: a single arm clinical trial.

BACKGROUND: The timed-sequential chemotherapy regimen consisting of etoposide, mitoxantrone and cytarabine (EMA) is an effective therapy for relapsed or refractory acute myelogenous leukemia (AML). We postulated that granulocyte colony-stimulating factor (G-CSF) might enhance the cytotoxicity of EMA by increasing the proportion of leukemic blasts in S-phase. We added G-CSF to EMA (EMA-G) for therapy of advanced high-risk AML patients. METHODS: High-risk AML was defined as refractory, relapsed or secondary to either an antecedent hematologic disorder or exposure to cytotoxic agents. The patients were treated with one course of EMA-G consisting of mitoxantrone and cytarabine on days 1-3, and etoposide and cytarabine on days 8-10. G-CSF was started on day 4 and continued until absolute neutrophil count recovered. RESULTS: Thirty patients were enrolled. The median age was 51 years (range, 25-75). Seventeen (61%) patients had unfavorable cytogenetic karyotypes. Twenty (69%) patients had secondary AML. Ten (34%) had relapsed disease. Four (14%) had refractory AML. Three (10%) patients died from febrile neutropenia and sepsis. Major non-hematologic toxicity included hyperbilirubimenia, renal insufficiency, mucositis, diarrhea, nausea and vomiting, skin rash. A complete remission was achieved in 13 (46%) patients. Median overall survival was 9 months (range, 0.5-66). Median relapse-free survival (RFS) for those who had a CR was 3 months (range, 0.5-63) with RFS censored at the time of allogeneic bone marrow transplantation or peripheral stem cell transplantation for 6 of the patients. CONCLUSIONS: EMA-G is a safe and efficacious option for induction chemotherapy in advanced, high-risk AML patients. The activity of EMA may be increased if applied in patients with less advanced disease.