Disseminated superficial actinic porokeratosis. Coexistence with other porokeratotic variants

The coexistence of disseminated superficial actinic porokeratosis (DSAP) with other variants of porokeratosis is rare. We report three such cases: DSAP with porokeratosis of Mibelli; DSAP with linear porokeratosis; and DSAP occurring in the mother of a girl with linear porokeratosis. Although different areas of skin and different family members usually express the same morphological variant, we suggest that the simultaneous expression of two closely linked gene loci could explain the coexistence of different porokeratotic variants.     

Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: a report from the Childhood Cancer Survivor Study

BACKGROUND: Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML). METHODS: This analysis included 272 5-year AML survivors who participated in the Childhood Cancer Survivor Study (CCSS). All patients were diagnosed at age < or =21 years between the years 1970 and 1986, and none underwent stem cell transplantation. Rates of survival, relapse, and late outcomes were analyzed. RESULTS: The average follow-up was 20.5 years (range, 5-33 years). The overall survival rate was 97% at 10 years (95% confidence interval [95%CI], 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8 recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95% CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent malignant neoplasms (SMN) were reported, including 4 with a history of radiation therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI, 2.1%-7.3%). Half of the survivors reported a chronic medical condition and, compared with siblings, were at increased risk for severe or life-threatening chronic medical conditions (16% vs 5.8%; P < .001). Among those aged > or =25 years, the age-adjusted marriage rates were similar among survivors and the general United States population (57% for both) and lower compared with siblings (67%; P < .01). Survivors' college graduation rates were lower compared with siblings but higher than the general population (40% vs 52% vs 34%, respectively; P < .01). Employment rates were similar between survivors, siblings, and the general population (93%, 97.6%, and 95.8%, respectively). CONCLUSIONS: Long-term survival from childhood AML > or =5-years after diagnosis was favorable. Late-occurring medical events remained a concern with socioeconomic achievement lower than expected within the individual family unit, although it was not different from the general United States population.     

Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia.

Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid cells (ID(50), 1-2 mM). Higher doses induce apoptosis. Patients with myelodysplasia (n = 11) and acute myeloid leukemia (n = 16) were treated with PB as a 7-day continuous infusion repeated every 28 days in a Phase I dose escalation study. The maximum tolerated dose was 375 mg/kg/day; higher doses led to dose-limiting reversible neurocortical toxicity. At the maximum tolerated dose, PB was extremely well tolerated, with no significant toxicities; median steady-state plasma concentration at this dose was 0.29 +/- 0.16 mM. Although no patients achieved complete or partial remission, four patients achieved hematological improvement (neutrophils in three, platelet transfusion-independence in one). Other patients developed transient increases in neutrophils or platelets and decrements in circulating blasts. Monitoring of the percentage of clonal cells using centromere fluorescence in situ hybridization over the course of PB administration showed that hematopoiesis remained clonal. Hematological response was often associated with increases in both colony-forming units-granulocyte-macrophage and leukemic colony-forming units. PB administration was also associated with increases in fetal erythrocytes. These data document the safety of continuous infusion PB and provide preliminary evidence of clinical activity in patients with myeloid malignancies.     

Safety of general anaesthesia and surgery in acute hepatic porphyria.

Patients with acute hepatic porphyria are denied essential operations because of concern that general anaesthesia and surgery will precipitate a life threatening porphyric crisis. This study assessed the safety of surgery under general anaesthesia in these patients. A combined prospective and retrospective case note study, with a biochemical study, was conducted in 25 patients with acute hepatic porphyria undergoing 38 surgical operations. Clinical outcome measures were survival and occurrence of porphyric crisis after surgery. The biochemical activity of porphyria was assessed by measurement of the perioperative 24 hour excretion of the haem precursors delta amino-laevulinic acid (ALA) and porphobilinogen (PBG). There were no deaths or crises after 29 operations in 19 patients who were known to have porphyria before their surgery, and therefore given only appropriate drugs. These operations include such major procedures as mitral valve replacement, hip replacement, coronary artery grafting, cholecystectomies, and renal transplantation. In eight of these patients the urinary excretion of ALA and PBG were studied, and showed no sustained postoperative increase. Nine operations were performed in eight patients before the diagnosis of porphyria was known and who thus received routine anaesthetic agents. Seven of these patients developed a postoperative porphyric crisis. Two of them died. It is concluded therefore that even the most major surgery can be undertaken safely in patients with porphyria. The risk is for undiagnosed cases.