Thiotepa and fractionated TBI conditioning prior to allogeneic stem cell transplantation for advanced hematologic malignancies: a phase II single institution trial.

Relapse of hematologic malignancies after allogeneic stem cell transplantation remains a common problem, in particular for patients who have advanced disease at the time of transplantation. Thiotepa has excellent antileukemic and immunosuppressive activity, and could therefore be a useful drug in the conditioning regimen for patients with advanced hematologic neoplasms. We retrospectively analyzed toxicity, engraftment and survival data of 41 patients who received a conditioning regimen of thiotepa (600 mg/m2) and hyperfractionated TBI (10 Gy) prior to matched related (n = 25) or matched unrelated (n = 16) allogeneic stem cell transplantation. The mean age at transplantation was 37.8 years (range 20-59), all but five patients had advanced hematologic malignancies at the time of transplantation. GVHD prophylaxis was with standard cyclosporine and methotrexate. Engraftment was excellent, but the regimen was associated with a high incidence of grade III renal (41%) and hepatic (15%) toxicity, and high transplant-related mortality (44% at day +90). The 3-year event-free survival was 13% and overall survival 14%. We conclude that this regimen requires modification to reduce toxicity.

Metallothionein isoform 3 overexpression is associated with breast cancers having a poor prognosis.

The third isoform (MT-3) of the metallothionein gene family is unique in that it has a limited tissue distribution, is not induced by metals, has a neuronal growth inhibitory activity, and sequesters zinc more effectively under zinc-depleted conditions. The goal of the present study was to determine whether MT-3 was absent in normal breast tissue, was overexpressed in breast cancers, and if MT-3 overexpression would be associated with disease outcome. A combination of immunohistochemistry and reverse-transcription polymerase chain reaction was used to demonstrate that the normal breast had no detectable expression of MT-3 mRNA or protein. Using immunohistochemistry, it was shown that MT-3 was overexpressed in 25 of 34 cases of breast cancer. In all cases of positive staining, MT-3 was diffusely localized to the cytoplasm. The tumors from these 34 cases were divided as to outcome based on known 5-year survival, with 20 patients being disease free at 5 years (good outcome) and the other 14 having recurring disease within 5 years (bad outcome). When analyzed for MT-3 staining, it was shown that there was a trend for increased MT-3 immunoreactivity in the group having bad outcomes. However, when the tumor subgrouping was further defined on the basis of carcinoma in situ (CIS), there was a marked significant difference in MT-3 staining between patients with good and bad outcomes. Limited to DCIS, MT-3 staining was significantly increased in patients with bad outcomes compared to those with good outcomes. Thus, these studies demonstrate that MT-3 is overexpressed in selected breast cancers and that overexpression is associated with tumors having a poor prognosis.

Guidelines for the use of blood transfusions.

Over 11 million units of red blood cells are transfused each year in the United States at a cost of over $2 billion. This paper reviews the indications for and the risks of red blood cell transfusions, and provides guidelines for transfusions in both surgical and non-surgical settings.

Current transfusion practices.

Utilization of packed red blood cells (PRBC) and plasma components individually or in combination allows replacement of the precise blood element needed, while avoiding some of the potential hazards of whole blood transfusions. Transfusion of PRBC, rather than whole blood, reduces the risk of circulatory overload and nonhemolytic transfusion reactions. Frozen PRBC essentially eliminate leukocyte or platelet sensitization and transmission of hepatitis is extremely rare.