Phellinus coronadensis: a new species from southern Arizona, USA.

Phellinus coronadensis is characterized and described morphologically as a new species from southern Arizona, USA. This fungus was previously reported as P. torulosus based on morphological similarities of the basidiomes and type of wood decay. However, P. coronadensis is restricted to two mountain ranges in southern Arizona and found almost exclusively on living southwestern white pine (Pinus strobiformis). Phellinus torulosus is found primarily in Europe and parts of Asia and is primarily associated with hardwood hosts. Based on sequence analysis of small subunit mitochondrial ribosomal DNA (mt-SSU), we determined that P. coronadensis is in a different lineage from P. torulosus and apparently more closely related to the P. pini complex. The taxon associated with southwestern white pine, being distinct and not yet having been validly named, is proposed as a new species here.

Role of adjuvant chemotherapy in the treatment of surgically resected pediatric nonrhabdomyosarcomatous soft tissue sarcomas: A Pediatric Oncology Group Study.

PURPOSE: To prospectively study the value of adjuvant chemotherapy in pediatric patients with surgically resected nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS). PATIENTS AND METHODS: From June 1986 to May 1992, after complete surgical resection (+/-radiotherapy) of their NRSTS, 81 eligible patients either received adjuvant chemotherapy comprising vincristine, dactinomycin, cyclophosphamide, and doxorubicin or were observed. Only 30 patients accepted randomization, and 15 were assigned to each regimen. Of the remaining 51 patients, 19 elected adjuvant chemotherapy and 32 elected observation. RESULTS: Patients were predominantly male, and 69% of all patients were white. The median age at diagnosis was 12.3 years (range, 9.2 to 20.7 years). For the 81 eligible patients, the 5-year overall survival estimate was 84.5% +/- 4.4% and event-free survival was 72.2% +/- 5.4%. Among randomized patients, the 5-year estimated overall survival rate was 93.3% +/- 7%, and the event-free survival rate was 86.7% +/- 9.5% for the observation group, compared with 69.2% +/- 13% and 40.7% +/- 14%, respectively, for those who received chemotherapy. The significantly worse outcome of patients who received adjuvant chemotherapy disappeared when survival was stratified by tumor grade. Among all patients, a grade 3 lesion conferred a significant disadvantage with respect to event-free survival (P =.0001). CONCLUSION: The administration of adjuvant chemotherapy according to the schedule and dosages used in our trial did not improve the outcome of children with resected NRSTS. In this study, tumor grade was the most important predictor of clinical outcome in patients with resected NRSTS, and this factor should be incorporated into the stratification of patients in future trials.

Interobserver variability in the detection of cervical-thoracic Hodgkin's disease by computed tomography.

PURPOSE: Computed tomography (CT) scans of the neck and chest are obtained at diagnosis of Hodgkin's disease to establish disease extent, plan radiotherapy, and serve as baseline studies for subsequent evaluation of response to therapy. However, differences in interpretation may occur even among experienced radiologists. This study was designed to test the extent of variation among expert radiologists' interpretations and to assess how their interpretations differed from that of the primary (institutional) radiologists. MATERIALS AND METHODS: Five radiologists independently reviewed randomly selected CT scans of 59 patients enrolled onto two Pediatric Oncology Group Hodgkin's disease treatment protocols. For each patient, 31 potential disease sites were scored as positive, negative, uncertain, or unassessable. Agreement among the reviewers and between the reviewers and the primary readers was analyzed. RESULTS: For 58% of the sites, at least four of the five reviewers agreed in >/= 80% of the cases. Kappa analysis showed moderate agreement in approximately two thirds of the sites and poor agreement in the remainder. There was moderate agreement between a majority of the expert readers and the primary radiologist reports for approximately one third of the sites, and agreement was poor in two thirds. CONCLUSION: There are disparities among radiologists' interpretations of cervical-thoracic CT imaging of patients with Hodgkin's disease. This variability may affect patient care and the performance and results of multi-institutional clinical trials. We propose that a standardized method of reporting might improve the consistency of interpretation of CT scans in these patients.

Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant.

Patients with delayed platelet recovery post-PBPC transplant (PBPCT) are a high-risk group for thrombocytopenic bleeding and platelet transfusion dependence. Total CD34+ cell dosage has been proposed as the most important factor influencing the rate of platelet recovery. To achieve the shortest time to platelet engraftment, a minimum leukapheresis target of 10x10(6) CD34+ cells/kg was established for 30 patients. Of the 29 evaluable patients, 62% had rapid (group I: time to platelets >20x10(9)/l < or =10 days and 50x10(9)/l < or =14 days) platelet recoveries while 38% had delayed (group II: 20x10(9)/l >10 days and 50x10(9)/l >14 days) recoveries. Groups I and II were compared for: (1) pretreatment variables; (2) mobilizing capability of CD34+ cells and subsets including megakaryocyte (Mk) progenitors; (3) infused dose of these cells at transplant; (4) changes in endogenous levels of Mpl ligand (or TPO) during mobilization and myeloablative chemotherapy. Group II patients received significantly more platelet transfusions (6 vs. 2.1, P = 0.002) post-PBPCT, had a higher proportion of patients with a prior history of BM disease (64% vs. 6%, P = 0.001), and showed a reduced ability to mobilize differentiated (CD34+/38+, CD34+/DR+) and Mk progenitors (CD34+/42a+, CD34+/61+). Only the number of Mk progenitors reinfused at transplant was significantly different between the groups (group II vs. group I: CD34+/42a+ = 1.02 vs. 2.56x10(6)/kg, P = 0.013; CD34+/61+ = 1.12 vs. 2.70x10(6)/kg, P = 0.015). The ability to mobilize Mk progenitors correlated with percentage changes in endogenous levels of TPO from baseline to platelet nadir during mobilization chemotherapy (CD34+/42a+: r = 0.684, P = 0.007; CD34+/61+: r = 0.684, P = 0.007), with group II patients experiencing lower percentage changes. An inverse trend but no correlation was observed between serial TPO levels and platelet counts. TPO levels remained elevated in group II patients throughout a prolonged period of thrombocytopenia (median days to 50x10(9)/l = 25 vs. 11 for group I), indicating that delayed engraftment was not due to a deficiency of TPO but to a lack of Mk progenitor target cells. Our results show that the number of reinfused Mk progenitors is a better predictor of platelet engraftment than total CD34+ cell dosage. Small changes in endogenous TPO levels during mobilization predict for low Mk progenitor yields.

Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.

PURPOSE: To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen. PATIENTS AND METHODS: Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin. RESULTS: The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. Twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P=.06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P=.03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia. CONCLUSION: This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients.

Modelling cure rates using the Gompertz model with covariate information.

We extend the modified Gompertz hazard function, first used by Cantor and Shuster for estimation of cure rates from pediatric clinical trials, by including covariate effects. The extended model provides a convenient method for estimation of the cure rate as a function of treatments and covariates.

Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation, and chemotherapy: a Pediatric Oncology Group study.

BACKGROUND: The objectives of this study were to compare vincristine/actinomycin D/cyclophosphamide/adriamycin (VACA) with VACA/plus imidazole carboxamide (DTIC) (VACAD) therapy in regards to complete/partial response and event free survival rates in children and adolescents with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) or previously chemotherapy-naive recurrent NRSTS or locally persistent gross residual tumor after surgery and radiation therapy. PROCEDURES: Between 1986 and March 1994, 75 patients entered this randomized study comparing VACA and VACAD, given at 3 week intervals. Sixty-one patients were considered eligible and received chemotherapy and radiation therapy to the primary tumor and areas of metastases. Thirty-six patients had regional unresected (Group III) disease, and 25 had metastatic disease (Group IV) at time of accession. Thirty-six patients received VACA (11 were not randomized), and 25 received VACAD. RESULTS: With a median follow-up of greater than 4 years, overall and event-free survival for all eligible patients are 30.6% and 18.4% respectively (S.E: 9.5% and 6.8%). There was insufficient evidence that DTIC offered any advantage to event free survival, but there was evidence for better outcome for patients in Group III disease in comparison to patients with Group IV disease, and for patients with a Grade 1 and 2 histology in comparison to Grade 3 lesions. CONCLUSIONS: Combination chemotherapy with VACA and VACAD were insufficient to prevent recurrent or progressive disease in children and adolescents with high stage NRSTS. The use of vincristine/ifosfamide/doxorubicin with cytokine support is under study.

Lymphocyte predominant Hodgkin disease: clinico-pathologic features and results of treatment--the Pediatric Oncology Group experience.

PURPOSE: In this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed. MATERIALS AND METHODS: From 1984-1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials. Patients' ages ranged from 3.1-17.8 years (mean of 12.9 years). There was a marked male predominance. RESULTS: Histologic subtypes were 17 nodular, 8 diffuse pattern; 1 was indeterminant. The sites involved at diagnosis were primarily the peripheral lymph nodes. Fourteen patients had stage (S) I disease; 9 had SII; 3 had SIII; there was no SIV disease. Only 4 of 26 patients had B symptoms. All 26 patients achieved complete remission, 10 with radiotherapy, 6 with chemotherapy and 10 with combined modality therapy. Treatment was not uniform since patients were registered on different protocols. Event-free survival after 5 years was 86.5 percent. Two patients developed and succumbed to large cell, T-cell type, non-Hodgkin lymphoma (NHL). CONCLUSIONS: Optimal treatment for LPHD should focus on efforts to limit the risk of second malignancy.

Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.

PURPOSE: To determine whether the addition of low-dose total-nodal irradiation (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have received eight cycles of alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when compared with patients who have received chemotherapy only. PATIENTS AND METHODS: At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV Hodgkin's disease were randomized to receive eight cycles of alternating MOPP-ABVD with or without low-dose TNI. RESULTS: Of 183 patients, four were rendered ineligible before treatment was initiated. One hundred sixty-one of 179 patients (90%) were in complete remission (CR) at the completion of eight cycles of alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to observation off therapy, whereas 80 of 161 were to receive combined modality therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive CMT did not receive radiation (RT) because of a protocol violation, but were monitored for EFS and OS and included in all analyses. The estimated EFS and OS rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The actuarial EFS at 5 years was 80% for patients who received CMT and 79% for patients who received MOPP-ABVD only. The OS for the former group is estimated to be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis and the attainment of a clinical CR after three cycles of chemotherapy were associated with a statistically significant improved EFS. CONCLUSION: Our results indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of low-dose RT does not improve the estimated EFS or OS in pediatric patients with advanced-stage Hodgkin's disease.

Meta-analysis and prospective meta-analysis in childhood leukemia clinical research.

In this paper, we consider the role of meta-analysis and 'prospective meta-analysis' studies in childhood acute lymphocytic leukemia (ALL). In this issue, Valsecchi and Masera [1] give a thoughtful discourse, generally favorable to this approach. This article presents the opposite point of view. The aims of our article are to present the implications in clinical, rather than biostatistical terms, and to provide an extensive literature review of the subject of meta-analysis. We conclude that treatment assessments, resulting from meta-analysis of closed studies (retrospective) should be met with healthy skepticism. Trials requiring international resources should be true intergroup trials with a single coordinating center, rather than prospective meta-analysis, unless it is a question grafted onto each group's own research agenda. For example, each group might ask its own systemic control question, but a CNS protection question is asked collectively.

A mating-type factors of Coprinus cinereus have variable numbers of specificity genes encoding two classes of homeodomain proteins.

We have identified the seven genes that constitute the A43 mating-type factor of Coprinus cinereus and compare the organisation of A43 with the previously characterised A42 factor. In both, the genes that trigger clamp cell development, the so-called specificity genes, are separated into alpha and beta loci by 7 kb of noncoding sequence and are flanked by homologous genes alpha-fg and beta-fg. The specificity genes are known to encode two classes of dissimilar homeodomain (HD1 and HD2) proteins and have different allelic forms which show little or no cross-hybridisation. By partial sequencing we identified a divergently transcribed HD1 (a1-2) and HD2 (a2-2) gene in the A43 alpha locus. a2-2 failed to elicit clamp cell development in three different hosts, suggesting that it is non-functional. a1-2 elicited clamp cells in an A42 host that has only an HD2 gene (a2-1) in its alpha locus, thus demonstrating that the compatible A alpha mating interaction is between an HD1 and an HD2 protein. The A43 beta locus contains three specificity genes, the divergently transcribed HD1 and HD2 genes b1-2 and b2-2 and a third HD1 gene (d1-1) that was shown by hybridisation and transformation analyses to be functionally equivalent to d1-1 in A42. An untranscribed footprint of a third A42 HD1 gene, c1-1, was detected between the A43 b2-2 and d1-1 genes by Southern hybridisation.

Comparison of two b1 alleles from within the A mating-type of the basidiomycete Coprinus cinereus.

We cloned and sequenced the b1 specificity gene, b1-2, from the A43 mating-type locus of the basidiomycete Coprinus cinereus, to compare its molecular structure to a previously published allele. The b1-2 gene was identified and isolated using a transformation assay for A-activity. The nucleotide (nt) sequence was determined and compared to the published sequence for the b1 specificity gene of the A42 mating-type locus. Both genes map to the same physical location within the A mating-type locus and conserved structural organization is observed at both the genomic and the protein level. Sequence alignments show that the two alleles share 73% overall nt sequence identity for the open reading frames (ORFs) and 68% overall amino acid (aa) sequence identity for the deduced polypeptides. Allowing for conservative substitutions, the overall aa sequence similarity is 79%. Comparison of the deduced aa sequences reveals several conserved structural motifs, including a DNA-binding homeodomain, putative bipartite nuclear localization signal sequences, and four predicted dimerization motifs. Regions rich in Pro and hydroxylated aa (Ser and Thr) are also common to both alleles. Sequence similarity varies greatly along the length of the gene at both the nt and aa levels. In general, similarity increases progressively from the N- to the C-terminal end with variable patterns of similarity observed for individual exons and the predicted motifs they encode. The low sequence similarity observed in the N terminus suggests that variability in this region may be involved in non-self recognition. Differing levels of positional and compositional constraint are apparent for different functional domains.