Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS.

Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

First two cases of immune hemolytic anemia associated with ceftizoxime.

BACKGROUND: Second- and third-generation cephalosporins have been associated with immune-mediated hemolytic reactions. This report discusses two patients who developed clinically significant extravascular hemolysis while receiving the third-generation cephalosporin ceftizoxime (Ceftizox). This is believed to be the first time hemolysis has been described in patients receiving this drug. STUDY DESIGN AND METHODS: Immunologic workup of drug-dependent antibodies was performed on blood samples using drug-coated and immune complex methodologies. Antibody classes and titers were analyzed. RESULTS: Both the patients' sera contained anti-ceftizoxime that reacted with red cells only when ceftizoxime was added to the sera ("immune complex" method). The patients recovered without complications following discontinuation of the drug. Each patient had IgM and IgG drug-dependent antibodies. The drug-induced antibodies from each patient cross-reacted with cefotaxime, which is structurally similar to ceftizoxime, but cross-reacted either weakly or not at all with ceftriaxone, which has a more complex side chain. CONCLUSION: This report describes the first cases of immune hemolytic anemia associated with ceftizoxime. In drug-induced hemolytic reactions, prompt recognition and discontinuation of the drug may be important factors in reducing the chance of serious sequelae.

Use of a tumor-cell enrichment column for the enhanced detection of minimal residual disease in the BM or apheresis peripheral blood transplant products of breast-cancer patients.

BACKGROUND: Contaminating tumor cells present in the BM or apheresis peripheral blood (APB) autologous transplant products have been shown to contribute to relapse following high-dose chemotherapy and stem-cell rescue (HDC/ASCR). Enhanced methods for tumor detection in BM or APB products for breast-cancer patients are required. METHODS: We evaluated a laboratory-scale tumor-cell enrichment column (TEC) as an enhanced method of detecting tumor cells in APB or BM of breast-cancer patients. Seventeen women with breast cancer (14 Stage IV and three Stage III) were evaluated using the TEC for residual tumor cells present in 20 samples of APB or BM biopsies following HDC/ASCR. RESULTS: Using conventional histological staining methods (without TEC), only one patient had evidence of tumor cells present in the BM biopsy, while 16 patients had negative biopsies. Using the TEC for tumor cell capture and immunocytochemical (ICC) staining with anti-cytokeratin MAb (CAM 5.2) for tumor detection, we were able to positively identify tumor cells in 20 samples (14 BM aspirates and six APB products). In 15 samples (nine BM and six APB), we used CAM 5.2 to positively identify cytokeratin(+) cells prior to using the TEC. However, positive cells were detected only after using the TEC in the remaining five samples. The level of sensitivity was significantly enhanced (p < or = 0.05) by 100-400 fold in the post-TEC (absorbed) fraction compared with the pre-TEC (post-Ficoll) fraction. DISCUSSION: We conclude from this study that the use of TEC improves our ability to detect residual breast-cancer cells in the APB or BM and could be potentially utilized to purge contaminating tumor cells from the stem-cell transplant.

Lamellar body number density and the prediction of respiratory distress.

The determination of amniotic fluid lamellar body number density (LBND) has recently been shown to correlate well with other established indicators of fetal lung maturity. The authors have compared the LBND with a fetal lung phospholipid profile in predicting the clinical outcome in 52 well-documented cases. If a cutoff of 30,000/microL was used to indicate fetal lung maturity, there were no false-negative results for the LBND whereas there was one for the fetal lung profile. On the other hand, this cutoff resulted in 22 false-positive results for the LBND, whereas there were only 7 false-positive results by the fetal lung profile. The number of false-positive results by the LBND can be decreased by using a separate cutoff of less than 10,000/microL to indicate high risk for development of respiratory distress, while leaving the cutoff for predicting mature lung at 30,000/microL. This resulted in only four false-positive results for the LBND; each of these were from the same patients who also had false-positive results by the fetal lung profile. Care must be taken to ensure that the particle counter used is properly calibrated and that the appropriate cutoffs for both lung maturity and immaturity are used.