Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation.

Busulfan (Bu)-based preparative regimens have not been extensively investigated in Hodgkin disease (HD). The purposes of this study were to investigate the toxicity and efficacy of a novel preparative regimen of Bu 14 mg/kg, etoposide 50-60 mg/kg, and cyclophosphamide 120 mg/kg in patients with primary refractory and relapsed HD. One hundred twenty-seven patients with a median age of 33 years (range, 14-67 years) underwent transplantation. The regimen was well tolerated, with 5.5% treatment-related mortality at 100 days after transplantation. With a median follow up of 6.7 years, the 5-year progression-free survival was 48 +/- 5%, and the 5-year overall survival was 51 +/- 5%. A Cox proportional hazards model identified refractory disease at time of transplantation as the only significant factor affecting relapse and overall survival, whereas disease bulk >10 cm affected overall survival. Five patients died between 5.3 and 9.3 years of late complications, including secondary myelodysplasia or acute myeloid leukemia, secondary solid malignancies, and pulmonary toxicity. This novel Bu regimen is comparable to other radiation-free preparative regimens in its effectiveness in the control of HD and with a low-risk of early treatment-related mortality.     

Nonhematopoietic tumor cells express functional GM-CSF receptors

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the colony growth of myeloid progenitors in semisolid media, and enhances the function of mature effector cells, including neutrophils, monocytes, and eosinophils. Small cell carcinoma lines (SCCL) have properties of amine precursor uptake and decarboxylation (APUD) cells and express high levels of the enzyme, L-aromatic amino acid decarboxylase. We looked for possible expression of GM-CSF receptors on nonhematopoietic cells and found specific high-affinity binding of human GM-CSF to SCCL and to the SV40-transformed African green monkey kidney cell line, COS. The small cell carcinoma lines responded to GM-CSF with enhanced proliferation, and both small cells and COS cells were found to express authentic 84,000 dalton GM-CSF receptor protein. These findings indicate that nonhematopoietic cells can bind and respond to GM-CSF, suggesting additional biological activities as well as the possibility of tumor responses when GM-CSF is used therapeutically in humans. Since preliminary clinical trials using CSFs as adjunctive treatment in patients with solid tumors are underway, it will be important to consider the possible responsiveness of nonhematopoietic tumor cells to CSFs.     

Additional translocation (9;12)(p13;q24.1) in newly diagnosed chronic myeloid leukemia: complete cytogenetic remission after interferon therapy

We report the case of a patient with chronic phase CML who exhibited, in the same cells, beside the Philadelphia chromosome, an additional translocation between the other chromosome 9 and one of the chromosomes 12 [t(9;12)(p13;q24.1)]. Complete cytogenetic remission with disappearance of both karyotypic abnormalities was achieved after 18 months treatment with low dose (1.4 × 10⁶ U/m²/day) recombinant alpha-interferon and has been sustained with maintenance therapy for 68⁺ months (actual follow-up). Clonality at diagnosis and recovery of polyclonal hematopoiesis in complete cytogenetic remission were demonstrated using the polymorphism at the human androgen receptor gene (Humara) locus on chromosome X. The role of the additional translocation in the response to low dose alpha-interferon therapy remains hypothetical.     

The prevalence of Down syndrome in County Galway

This is a retrospective survey of all cases of Down syndrome recorded between 1981 and 2000 to mothers resident in Co. Galway. The study compares the incidence of Down syndrome in both decades and examines the effects of changing demographics on incidence rates. The overall prevalence rate was 26.8/10,000 live births for the full period. Although there were 5119 fewer births in the 1991-2000 period, the prevalence was 29.8/10,000 compared to 24.1/10,000 in the previous decade. Despite the falling birth rates and fertility rates observed in our study between the two decades we found that the higher prevalence of Down syndrome in the second decade was directly related to the significant increase in the proportion of women in the 30 plus age group. Our study also found the place of the child with Down syndrome in the family changed, with 25.3% being the 5th or more child in the first decade compared with 9.5% in the second decade.     

The great imitator with no diagnostic test: pyoderma gangrenosum

Pyoderma gangrenosum is a rare, neutrophil‐mediated, auto‐inflammatory dermatosis that wound care specialists must be prepared to recognise. This condition has clinical features analogous to infectious processes. There is no specific diagnostic test and the diagnosis is usually obtained from exclusion. Its early recognition and proper management with prompt initiation of immunosuppressive therapy are essential to improve the quality of life and the prognosis of patients.     

A single gene for lycopene cyclase, phytoene synthase, and regulation of carotene biosynthesis in Phycomyces

Previous complementation and mapping of mutations that change the usual yellow color of the Zygomycete Phycomyces blakesleeanus to white or red led to the definition of two structural genes for carotene biosynthesis. We have cloned one of these genes, carRA, by taking advantage of its close linkage to the other, carB, responsible for phytoene dehydrogenase. The sequences of the wild type and six mutants have been established, compared with sequences in other organisms, and correlated with the mutant phenotypes. The carRA and carB coding sequences are separated by 1,381 untranslated nucleotides and are divergently transcribed. Gene carRA contains separate domains for two enzymes, lycopene cyclase and phytoene synthase, and regulates the overall activity of the pathway and its response to physical and chemical stimuli from the environment. The lycopene cyclase domain of carRA derived from a duplication of a gene from a common ancestor of fungi and Brevibacterium linens; the phytoene synthase domain is similar to the phytoene and squalene synthases of many organisms; but the regulatory functions appear to be specific to Phycomyces.     

Revisiting the sponge sources, stereostructure, and biological activity of cyclocinamide a

The dramatic biogeographical variations in the secondary metabolites from Psammocinia aff. bulbosa have complicated our efforts to reisolate the two most cytotoxic of its metabolites, (+)-psymberin and (+)-cyclocinamide A. Reported now are the results of a new study that demonstrates our ability to repeatedly isolate these two compounds through targeted collection efforts. Additional study of the new sample of (+)-cyclocinamide A has enabled finalizing its biological activity and absolute stereochemistry as 4S, 7S, 11S, 14S.