Myeloproliferative disorder with eosinophilia and ETV6-ABL gene rearrangement: efficacy of second-generation tyrosine kinase inhibitors.

ETV6/ABL is a rare gene rearrangement that has rarely been detected in Philadelphia-negative chronic myeloproliferative disorders (C-MPD) and found to have tyrosine kinase activity similar to the BCR/ABL fusion protein. We describe a case of a 61-year-old female with a C-MPD associated with an ETV6/ABL gene rearrangement. She achieved complete cytogenetic remission on imatinib 400mg daily for 17 months, but then developed morphologic and cytogenetic relapse. After starting nilotinib 400mg orally twice daily, she achieved CCyR at 3, 6, and 11 months, suggesting that second-generation TKIs can result in favorable responses in patients with ETV6/ABL rearrangement who relapse after imatinib.

Myeloid sarcoma presenting as an isolated nodule in a patient with acute myelogenous leukemia.

We report a case of an elderly female in remission from acute myelogenous leukemia that presented with a nonhealing enlarging asymptomatic nodule on her right thigh. A wide excision of the nodule and histological examination revealed myeloid sarcoma without evidence or overlap of leukemia cutis, which had been suspected from nodules that had developed early in the course of the disease. The patient subsequently underwent radiation therapy to the area with sustained clearance.

Positive heparin-platelet factor 4 antibody complex and cardiac surgical outcomes.

BACKGROUND: Given the large number of patients undergoing cardiac operations annually, it is important to identify populations at high risk for adverse outcomes. This observational study was conducted to determine the incidence of preoperative heparin-platelet factor 4 (HPF4) antibodies and to assess the associated risk of postoperative adverse outcomes in a nonselected cardiac surgery patient population. METHODS: Between March 2002 and December 2004, 1114 (92%) of 1209 patients undergoing cardiac surgery with heparin were tested in an unselected manner for HPF4 antibodies. Main outcome measures were HPF4 antibody seropositivity and fatal and nonfatal adverse clinical outcomes after cardiac surgery. RESULTS: Of those screened, 60 (5.4%) of 1114 had positive HPF4 antibodies preoperatively. These patients had longer mean postoperative length of stay (14.0 days versus 9.8 days, p = 0.05), a higher incidence of prolonged (> or = 96 hours) mechanical ventilation (20.3% versus 9.2%, p = 0.02), acute limb ischemia (5.1% versus 0.9%, p = 0.03), renal complications including dialysis (20.3% versus 10.5%, p = 0.03), and gastrointestinal complications (15.3% versus 5.9%, p = 0.01). Stepwise logistic regression analysis showed positive HPF4 antibody status to be an independent predictor for adverse outcome and was associated with a higher risk for renal complications, including dialysis (adjusted odds ratio 2.2; 95% confidence interval, 1.1 to 4.3), than was diabetes. CONCLUSIONS: In this large patient series, the presence of HPF4 antibodies before surgical heparin administration was an independent and clinically significant risk factor for postoperative adverse events after cardiac surgery. An optimal preoperative cardiac surgery risk profile should include HPF4 antibody status.

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets.

Thrombocytopenia, often severe, occurs in 1% to 2% of patients given the fibrinogen receptor antagonist abciximab, a chimeric Fab fragment containing murine specificity-determining and human framework sequences. The cause of this complication has not yet been defined. Studies of 9 patients who developed profound thrombocytopenia (platelets <10 x 10(9)/L [10 000/microL]) within a few hours of being given abciximab a second time showed that each had a strong immunoglobulin G (IgG) antibody that recognized platelets sensitized with abciximab. Five patients also had IgM antibodies. IgG antibodies reactive with abciximab-coated platelets were also found in 77 (74%) of 104 healthy subjects. However, the patient antibodies could be distinguished from "normal" ones in 2 ways: (1) only the patient antibodies reacted preferentially with platelets sensitized with the intact monoclonal antibody 7E3 from which the murine sequences in abciximab are derived; and (2) the "normal" antibodies could be inhibited by Fab fragments derived from normal human IgG, whereas the patient antibodies were relatively resistant to this treatment. The findings suggest that antibodies from the patients are specific for murine sequences in abciximab and are capable of causing life-threatening thrombocytopenia upon injection of this drug. The antibodies commonly found in healthy subjects are specific for the papain cleavage site of any Fab fragments and, although they react with abciximab-coated platelets, appear not to cause significant thrombocytopenia. It may be possible to identify patients at risk for developing thrombocytopenia if given abciximab by screening for antibodies that recognize 7E3-coated platelets.

Pentoxifylline, Ciprofloxacin and Dexamethasone Improve the Ineffective Hematopoiesis in Myelodysplastic Syndrome Patients; Malignancy.

Twenty-five patients with a diagnosis of myelodysplastic syndromes (MDS) were randomized to either begin therapy with pentoxifylline, ciprofloxacin and dexamethasone (PCD) immediately (10 patients) or after a 12 week observation period (control arm, 15 patients). PCD was administered with the goal of suppressing cytokine-induced excessive intramedullary apoptosis of hematopoietic cells. No marked fluctuations of blood counts were noted during the period of observation. Twenty-two patients completed at least 12 weeks of therapy: 18/22 showed some type of hematologic response, 9/18 showing an improvement in absolute neutrophil count only (p = < 0.001) and 9/18 showing multi-lineage responses. No unique category of MDS responded better, however 19/25 patients had refractory anemia (RA)/RA with ringed sideroblasts. The median time to response was 6 weeks and 3/18 responding patients maintained their responses beyond a year. We conclude that hematologic improvement in response to PCD therapy supports the validity of this unique anti-cytokine approach. Future trials should combine PCD therapy with established approaches (growth factors/chemotherapy) and also should focus on identifying more effective ways of suppressing the pro-apoptotic cytokines in MDS.