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D Becton

Publications and source records attributed to D Becton.

8 recordsLinked to original sources
PubMed2005

Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000.

From 1981 to 2000, a total of 1823 children with acute myeloid leukemia (AML) enrolled on four consecutive Pediatric Oncology Group (POG) clinical trials. POG 8101 demonstrated that the induction rate associated with the 3+7+7 combination of daunorubicin, Ara-C, and 6-thioguanine (DAT) was greater than that associated with an induction regimen used to treat acute lymphoblastic leukemia (82 vs 61%; P=0.02). Designed as a pilot study to determine the feasibility of administration of noncross-resistant drug pairs and later modified to assess the effect of dose intensification of Ara-C during the second induction course, POG 8498 confirmed the high initial rate of response to DAT (84.2%) and showed that dose intensification of Ara-C during the second induction course resulted in a trend toward higher event-free survival (EFS) estimates than did standard-dose DAT (2+5) during the second induction course (5 year EFS estimates, 22 vs 27%; P=0.33). Age <2 years and leukocyte count <100 000/mm3 emerged as significantly good prognostic factors. The most significant observation made in the POG 8498 study was the markedly superior outcome of children with Down's syndrome who were treated on the high-dose Ara-C regimen. POG 8821 compared the efficacy of autologous bone marrow transplantation (BMT) with that of intensive consolidation chemotherapy. Intent-to-treat analysis revealed similar 5-year EFS estimates for the group that underwent autologous BMT (36+/-4.7%) and for the group that received only intensive chemotherapy (35+/-4.5%) (P=0.25). There was a high rate of treatment-related mortality in the autologous transplantation group. The study demonstrated superior results of allogeneic BMT for patients with histocompatible related donors (5-year EFS estimate 63+/-5.4%) and of children with Down's syndrome (5-year EFS estimate, 66+/-8.6%). The POG 9421 AML study evaluated high-dose Ara-C as part of the first induction course and the use of the multidrug resistance modulator cyclosporine. Preliminary results showed that patients receiving both high-dose Ara-C for remission induction and the MDR modulator for consolidation had a superior outcome (5-year EFS estimate, 42+/-8.2%) than did patients receiving other treatment; however, the difference was not statistically significant. These four studies demonstrate the importance of dose intensification of Ara-C in the treatment of childhood AML; cytogenetics as the single most prognostic factor and the unique curability of AML in children with Down's syndrome.

Acute Disease↗
PubMed2001

High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A.

An open-label multicentre trial was conducted to evaluate high-dose DDAVP (desmopressin acetate) intranasal spray (Stimate; 1.5 mg mL(-1)), for the control of bleeding in 333 patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease, or symptomatic carriers of haemophilia A. Overall, 278 patients received 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)). Using study-defined guidelines, patients evaluated the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) as 'excellent' or 'good' in 743 (95%) of 784 bleeding episodes. It demonstrated 'excellent' results in 384 (93%) of 413 administrations for prophylaxis and in eight of eight uses prior to acute surgical or dental procedures. When used for the treatment of menorrhagia, the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) was rated as 'excellent' after 655 (92%) of 721 daily uses. Of 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)), 172 (8%) were associated with adverse events. A total of 272 adverse events were reported among 80 patients. Of these, 239 (88%) were mild or moderate in intensity and only one patient was removed from the study due to an adverse event. These results demonstrate the safety and efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) for control of bleeding episodes in patients with mildly decreased levels of factor VIII, von Willebrand factor, or both.

Administration, Intranasal↗
PubMed2000

BP1, a new homeobox gene, is frequently expressed in acute leukemias.

Aberrant expression of homeobox genes has been described in primary leukemia blasts. We recently cloned a new cDNA, BP1, which is a member of the homeobox gene family. BP1 expression was investigated in bone marrow samples from acute myeloid leukemia (AML), acute T cell lymphocytic leukemia (ALL) and pre-B cell ALL. Expression levels of two apparent isoforms of BP1, DLX7 and DLX4, were measured in the same samples. They are weakly if at all detectable in normal bone marrow, PHA-stimulated T cells or B cells. BP1 RNA was highly expressed in 63% of AML cases, including 81% of the pediatric and 47% of the adult cases, and in 32% of T-ALL cases, but was not found in any of the pre-B ALL cases. Coexpression of BP1, DLX7 and DLX4 occurred in a significant number of leukemias. Our data, including co-expression of BP1 with c-myb and GATA-1, markers of early progenitors, suggest that BP1 expression occurs in primitive cells in AML. Analysis of CD34+ and CD34- normal bone marrow cells revealed BP1 is expressed in CD34- cells and virtually extinguished in CD34+ cells. Ectopic expression of BP1 in the leukemia cell line K562 increased clonogenicity, consistent with a role for BP1 in leukemogenesis. The presence of BP1 RNA in leukemic blasts may therefore be a molecular marker for primitive cells and/or may indicate that BP1 is an important upstream factor in an oncogenic pathway.

Acute Disease↗
PubMed1994

Karyotype evolution in a patient with Down syndrome and acute leukemia following a congenital leukemoid reaction.

We report the serial cytogenetic study of a patient with Down syndrome who experienced a congenital leukemoid reaction, underwent a spontaneous remission within four months, and subsequently developed acute myeloid leukemia at 16 months. A blood chromosome study to rule out Down syndrome performed at age 24 days, during the leukemoid reaction, revealed a 47,XX,+21 karyotype. The diagnosis of acute leukemia was made at 16 months, at which time a chromosome study, on bone marrow, was performed. This analysis revealed a clonal karyotype of 47,XX,+21,-22,+der(22)t(1;22)(q21;q13) in all but one cell studied. The single apparently nonclonal cell showed a karyotype of 49,XX,+12,-13,-19,+der(19)t(19;?)(q11;?)x2,+21,+22. A third chromosome study at 19 months indicated the original leukemic clone with t(1;22) (q21;q13) had been replaced by the clone represented by the single cell with 49 chromosomes seen in the previous chromosome study. This case of an infant with Down syndrome and acute leukemia illustrated rapid evolution and a transitory nature to clonal chromosome aberrations while retaining AML morphology and course.

Acute Disease↗
PubMedDate not supplied

Thyroid carcinoma after successful treatment of osteosarcoma: a report of three patients.

We report three cases of papillary thyroid carcinoma occurring after successful treatment of osteosarcoma. Only one of the three patients received radiation therapy (to the chest) as part of the primary treatment of osteosarcoma. The onset of thyroid carcinoma occurred between 8 and 16 years from the cessation of osteosarcoma therapy. All patients are alive and disease-free from both malignancies. Whereas the association between osteosarcoma and thyroid carcinoma has not previously been recognized, there have been five case reports of these two entities occurring in the same patient. Three of these cases occurred in patients with Werner syndrome. None of the patients reported here had physical stigmata of Werner syndrome or a family history consistent with a hereditary cancer syndrome. Thyroid carcinoma occurs infrequently in patients with osteosarcoma, but in view of the rarity of these two disorders, this association may represent an inherited predisposition to these malignancies.

Adolescent↗