Single-dose dexamethasone for the prevention of pemetrexed associated cutaneous adverse reactions.

Pemetrexed (Alimta®) is a novel anti-folate antimetabolite agent that is used in combination with cisplatin for the treatment of patients with unresectable malignant pleural mesothelioma and as a single agent or in combination with cisplatin for patients with locally advanced or metastatic non-small-cell-lung-cancer. Cutaneous adverse reactions are common side effects of pemetrexed for which the manufacturer recommends 3-day premedication with dexamethasone 4 mg by mouth twice daily-(the day before, the day of, and the day after treatment). Patients' adherence to this premedication regimen is of concern. We report 14 cases of metastatic non-small-cell-lung-cancer patients who were premedicated with a single dose of dexamethasone 20 mg prior to pemetrexed or pemetrexed-based chemotherapy. None of these patients reported a grade 3 or above skin reactions over the course of their treatments. These findings suggest that a single dose of dexamethasone 20 mg may be an alternative premedication regimen in patients with metastatic non small cell lung cancer receiving pemetrexed or pemetrexed-based chemotherapy.

Safety and efficacy of FOLFOX followed by cetuximab for metastatic colorectal cancer with severe liver dysfunction.

Both 5-FU and oxaliplatin have been used as single agents in patients with colorectal cancer and severe liver dysfunction, but the combination of these drugs has not yet been investigated. A 67-year-old man diagnosed with colorectal cancer in 2008 presented in April 2011 to Appalachian Regional Healthcare Cancer Center with obstructive jaundice and weight loss. Imaging studies were compatible with a liver mass and dilatation of the intrahepatic bile ducts. A liver biopsy confirmed metastatic colorectal cancer. Because his total bilirubin level was 23.1 mg/dL, a percutaneous catheter was placed in May 2011. His total bilirubin level decreased to 5.9 mg/dL, but then increased to 9.4 mg/dL in June 2011. He was started on a FOLFOX regimen, with a 50% dose reduction of 5-FU bolus (200 mg/m(2)) and continuous infusion (1200 mg/m(2)) over 46 hours, and a 15% dose reduction of oxaliplatin (75 mg/m(2)) every 2 weeks. He tolerated this regimen very well, with normalization of his bilirubin level, a significant decrease in his tumor markers, and a partial response seen on PET/CT scan. His only significant toxicity was a grade 2 stomatitis. He received 21 cycles of FOLFOX, and was later switched to cetuximab treatment after disease progression. These findings suggest that FOLFOX might be effective in metastatic colon cancer with severe liver dysfunction, with minimal toxicity, and deserves further investigation.

Influence of related donor age on outcomes after peripheral blood stem cell transplantation.

BACKGROUND AIMS: The rising use of allogeneic transplantation in older recipients necessitates considering older related donors. The effect of related donor age for peripheral blood stem cell allografts (PBSC) on graft maintenance and outcomes, independent of CD34(+)cell dose, has not been well-characterized. METHODS: HLA-related donors (98% siblings) underwent a uniform filgrastim-based mobilization regimen aiming to collect and infuse 5 × 10(6) CD34(+) cells/recipient kg. Donor and recipient age were modeled in multiple ways to account for the correlation, and outcomes reported by decade of donor age. RESULTS: The median donor and recipient ages were 52 years and 54 years, respectively. The mean CD34(+) cell dose infused was 5.6 × 10(6) CD34(+)/kg and 75% of patients received a narrow range between 4.4 and 6.6 × 10(6) CD34(+) cells/kg. Neither better PBSC mobilization nor higher CD34(+) content of allografts was significantly associated with engraftment or transplant outcomes. After adjusting for recipient age and other prognostic factors, older donor age by decade conferred a lower risk of non-relapse mortality (NRM) [hazard ratio (HR) = 0.64, 95% confidence interval (CI) 0.45-0.91, P = 0.013] and borderline improvement in overall survival (OS) (HR = 0.76, 95% CI 0.58-0.99, P = 0.045) without altering progression-free survival (PFS) (HR = 0.85, 95% CI 0.66-1.07, P = 0.18). CONCLUSIONS: Older donor age does not worsen outcome after matched related donor PBSC transplantation in patients receiving a narrow range CD34(+) cells. The relatively small sample size mandates that the finding of similar to improved outcomes for older related donor age must be confirmed in larger studies.

Persistent hypocalcemia associated with therapeutic plasma exchange performed to reduce HLA antibody levels in cardiac transplant recipients.

BACKGROUND: Patients who receive heart transplants may undergo therapeutic plasma exchange to reduce high levels of HLA antibodies which may increase the risk of allograft rejection. Plasma exchange may predispose to hypocalcemia because of chelation of calcium by sodium citrate, used as an anticoagulant both during the procedure and in thawed fresh frozen plasma often used for replacement. METHODS: We report three adults with dilated cardiomyopathy who underwent cardiac transplantation and serial plasma exchange for high levels of HLA antibodies. We followed these patients' pre-exchange serum calcium levels and the quantity of calcium supplementation they received. Further, we examined myocardial tissue sections post-transplantation for calcium deposition. RESULTS: Our patients' serum calcium levels were initially normal, but, despite aggressive calcium repletion, remained low (nadirs for pre-exchange ionized calcium in two patients 4.48 and 3.8mg/dL, respectively, reference range 4.6-5.4mg/dL). For patient 3, pre-exchange total calcium on day 2 was 7.9mg/dL (reference range 8.4-10.2mg/dL). Two patients had intermittent symptoms of hypocalcemia. Studies of cardiac tissue sections (available only from these two patients) were consistent with the presence of calcium deposition post transplantation. In comparison, six patients who underwent lung transplantation and plasma exchange for high levels of HLA antibodies did not manifest significant hypocalcemia. CONCLUSIONS: We emphasize the need for prompt and sufficient calcium replacement, monitored by serum ionized calcium levels, in the early post-cardiac transplantation period when plasma exchange is performed with thawed fresh frozen plasma replacement. The persistently low serum calcium levels we observed post heart transplantation were possibly contributed to by increased myocardial calcium influx.

Adjunct therapeutic plasma exchange for anti-N-methyl-D-aspartate receptor antibody encephalitis: a case report and review of literature.

Encephalitis associated with autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR) is usually a paraneoplastic syndrome that presents in young females with ovarian teratomas. We report a case of a previously healthy 14-year-old girl with sudden-onset paranoia, hallucinations, hyperactivity, increased speech, decreased sleep, seizures, and violent behavior deteriorating to catatonia. Her cerebrospinal fluid tested positive for anti-NMDAR antibodies. She was treated with five sessions of therapeutic plasma exchange (TPE) after having failed therapy with antibiotics, intravenous steroids, intravenous immunoglobulin (IVIG), one dose of rituximab, and seven sessions of electroconvulsive therapy (ECT). The American Society for Apheresis assigns a Category III (Grade 2C) recommendation for TPE in paraneoplastic neurologic syndromes; however, apheresis specifically for anti-NMDAR encephalitis has not been well studied. Literature review revealed two case reports describing outstanding improvement in patients with anti-NMDAR encephalitis following TPE. We report no improvement in our patient's symptoms after plasma exchange and discuss possible reasons for why it failed along with review of the literature.

Polyethylene glycol antiglobulin tube versus gel microcolumn: influence on the incidence of delayed hemolytic transfusion reactions and delayed serologic transfusion reactions.

BACKGROUND: Our institution has reported on delayed hemolytic transfusion reaction (DHTR) and delayed serologic transfusion reaction (DSTR) incidence changes. From January 1993 to June 2003, a polyethylene glycol (PEG) tube-based technique was used for red blood cell (RBC) antibody screen. In June 2003, a gel microcolumn technique was implemented. Impact of this on antibody detection and DHTR and DSTR incidence was investigated. STUDY DESIGN AND METHODS: Positive antibody screen frequency and antibody specificity from January 2002 to March 2003 and July 2003 to September 2004 were compared. Overall incidence of DHTR and DSTR as well as the number and identity of the RBC antibodies implicated from August 1999 through June 2003 (PEG) and July 2003 through July 2007 (gel) were compared. The mean length of hospital stay (LOS) and number of RBC units transfused per patient were compared. RESULTS: Equivalent numbers of antibody screens were performed with equivalent numbers of positive screens. Significant differences were not seen in the detection of clinically significant antibodies but significantly fewer clinically insignificant antibodies were detected with gel. Ninety-six DHTRs and DSTRs were diagnosed. The LOS and number of transfused RBC units were not statistically different. A significantly higher incidence of DHTRs and DSTRs was seen with PEG compared to the gel. CONCLUSION: The gel microcolumn method is similar to the PEG in detecting clinically significant antibodies but detects fewer clinically insignificant antibodies. The implementation of gel resulted in a lower incidence of DHTRs and DSTRs compared to PEG.

Older age but not donor health impairs allogeneic granulocyte colony-stimulating factor (G-CSF) peripheral blood stem cell mobilization.

We evaluated stem cell mobilization in 195 consecutive sibling donors who underwent a uniform mobilization regimen of granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg/day divided into twice daily dosing. On day 5, peripheral blood (PB) CD34 cells/microL were measured immediately prior to peripheral blood stem cell (PBSC) apheresis. Failed mobilization was defined as <20 CD34 cells/microL on day 5. The median age was 52 years and 73 (37%) were 55 years or greater. Comorbid conditions by the Charlson Comorbidity Index (CCI) occurred in 13%, but only 3% had Karnofsky performance status (PS) <100%. Eight (4%) failed mobilization, defined as <20 CD34 cells/microL on day 5. Older age was associated with fewer CD34 cells/microL (P=.002). In addition, 6/73 (8.2%) older donors failed mobilization compared to 2/122 (1.6%) younger donors (P=.054). Comorbidity, sex, race, and donor weight did not influence mobilization. Although low PS was very uncommon, it was associated with reduced mobilization (P=.021), but not mobilization failure. A small fraction of older donors mobilize poorly, and this is not explained by standard measures of comorbidity or PS.

Eluate testing following microscopically positive direct antiglobulin tests with anti-IgG.

The direct antiglobulin test (DAT) demonstrates the presence of immunoglobulin (eg, IgG) or complement on the surface of red blood cells (RBCs). Immunoglobulin can be removed from RBCs by elution. The liquid end-product of elution procedures, the eluate, can be evaluated by antibody identification procedures. Antibody identification studies following acid/EDTA elution and DATs performed in our immunohematology laboratory during 2005 were evaluated to determine the usefulness of eluate testing following a microscopically positive IgG DAT. In total, 310 eluates were prepared during the year 2005; 146 of these eluates were derived from RBC samples with a microscopically positive DAT. The remaining eluates were derived from RBC samples with macroscopically positive IgG DATs (85 were weakly +; 32 were 1+; 40 were 2+; and 7 were 3+). Data were collected for the number and types of new antibodies (warm autoantibodies or alloantibodies) that were identified as a consequence of eluate testing. The incidence of new alloantibodies in the microscopically positive group (0.7%) was significantly lower than the combined incidence in the macroscopically positive groups (5.5%, p = 0.02). Based on these results, the authors conclude that performing antibody identification procedures on acid/EDTA eluates derived from RBC samples with microscopically positive IgG DATs has limited utility.

The effect of double- and triple-apheresis platelet product donation on apheresis donor platelet and white blood cell counts.

BACKGROUND: Concerned about the effect of multiple platelet (PLT) product donation on donor health, in 2005 the FDA proposed restrictions limiting the number of PLT products donated in 12 months. This was based on limited published evidence. To provide information on the effect of PLT donation on PLT and lymphocyte (LYM) count, hematologic variables were examined in a group of multiple PLT product donors. STUDY DESIGN AND METHODS: Donors with at least two apheresis PLT donations, one of which was a double- or triple-PLT product, were examined. Donor demographics, number of blood donations, and number of apheresis PLT products donated were determined. Hematologic variables were evaluated at the first and last donation. RESULTS: A total of 471 donors (median age, 48.8 years; 55% male; median time between first and last donations, 72 weeks) were studied. The median number of PLT donations was 4 (range, 1-34) with the median number of PLT products donated being 7 (range, 2-65). The median PLT count demonstrated a significant increase (14 x 10(9)/L, p = 0.0001) while both white blood cell and LYM counts showed significant decreases (-0.2 x 10(9)/L, p = 0.0052; and -0.06 x 10(9)/L, p = 0.0001, respectively). After adjusting for sex and whole-blood donations, LYM count demonstrated a significant decline associated with both number of donations (-0.01 x 10(9)/L, p = 0.01) and number of products donated (-0.005 x 10(9)/L, p = 0.02). PLT count demonstrated a significant increase associated with number of products donated (0.42 x 10(9)/L, p = 0.03). CONCLUSION: Significant but small LYM decrease and PLT increase were seen. Limitations on the number of apheresis PLT products donated within 12 months do not seem warranted due to PLT or LYM count changes.