Eighty-four patients with typical chronic lymphocytic leukemia 27% of patients with B-CLL. [11][12][13] Fegan et al 13 studied 45 (CLL) (by morphological and immunophenotypic criteria) on patients with typical CLL over 5 years and performed cytowhom karyotypes were available were studied. Binet stage at genetic analysis every 6-12 months or more frequently if there diagnosis and follow-up were defined. Survival was calculated was evidence of disease progression. Abnormalities were from diagnosis. Fifty-one percent of patients had a karyotypic detected in 62% at some point during the study with 38% abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different surshowing clonal evolution. 11q deletions were found most frevival from patients with normal karyotype. The second comquently in the patients with progressive disease. This original monest abnormality was del(11q) (13%); these patients had sigstudy was extended to an adjacent centre and here we present nificantly worse survival when compared both with patients our updated long-term results. The patients' records were examined and the Binet stage was with CLL have chromosomal abnormalities as detected by noted at diagnosis and any change was documented. Treatcytogenetic analysis 1,2 but few centres perform routine cytogments for CLL were also recorded as were the causes of death. enetic analysis because of the perception that limited prognos-A patient was considered to have had a CLL-related death if tic information can be gained over and above that of the he/she died as a result of cytopenias, high-grade lymphoma Binet/Rai staging. The presence of a clonal abnormality, howor infection; also if CLL was quoted as the cause of death on ever, may be an aid in the diagnosis and assessment of progthe death certificate. Otherwise death was considered nonnosis. Deletions at 13q14 are the most frequent abnormality CLL related. In all cases survival was assessed from diagnosis. in CLL and occur in up to 30% of patients. 2-4 Such patients have been shown to have a similar survival pattern to those with a normal karyotype. 2 Trisomy 12 is another common abnormality, affecting about 20% of patients as determined Diagnosis of CLL by conventional techniques 2 but as many as 30-40% when analysed by FISH, detecting abnormalities in previously norThis required a peripheral lymphocytosis (Ͼ4 × 10 9 /l) of small mal karyotypes. 5,6 Trisomy 12 is thought to be an adverse mature lymphocytes, Ͻ10% prolymphocytes or large lymphoprognostic feature and correlation with atypical morphology cytes and Ͻ15% cleaved or lymphoplasmacytic cells. and poor survival has been shown. 2,6,7 Multiple karyotypic Immunophenotype of typical CLL was needed ie CD5, CD19 abnormalities, a high percentage of abnormal metaphases and and CD23 positive with weak immunoglobulin expression abnormalities of chromosome 14 are also associated with demonstrating or restriction. FMC7 was weak and/or poorer outlook; 2,8-10 at least a proportion of the latter wi...
SummaryWe report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.
Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R-1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post-autoBMT, and 12 d post-alloBMT. Attainment of 15 x 10(9)/l reticulocytes and 0.5 x 10(9)/l HFR at day 21 post-transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft-versus-host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR. Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation.
BACKGROUND: In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent/refractory lymphoma. METHODS: The authors escalated the dose of CXD101 from 1 mg twice daily orally for 5 days in a 21-day cycle (3+3 design). RESULTS: A total of 39 patients were enrolled, 36 of whom received CXD101. Of the 30 patients in the escalation cohort, 29 were evaluable for determination of the dose-limiting toxicity (DLT). DLTs were noted at doses of 16 mg twice daily (1 of 6 patients), 20 mg twice daily (1 of 6 patients), and 24/25 mg twice daily (2 of 5 patients, both of whom developed neutropenic fever). The MTD was 20 mg twice daily, which achieved maximal plasma concentrations (±standard deviation) of 231 ± 76 nM to 342 ± 126 nM, which was within the biologically active range. Six patients received 20 mg twice daily in an expansion cohort. The most frequent adverse events were fatigue, nausea, and reversible cytopenia. Key grade 3 to 4 adverse events (according to Common Terminology Criteria for Adverse Events criteria [version 4.03]) included thrombocytopenia (11%), neutropenia (17%), and neutropenic fever (2%) across the 133 CXD101 cycles given. The toxicity profile was similar to that of licensing studies with other histone deacetylase inhibitors. In 22 evaluable patients receiving a dose of ≥16 mg twice daily (17 of whom had lymphoma and 5 of whom had solid tumors), 3 partial responses (2 in patients with classic Hodgkin lymphoma after allogenic stem cell transplantation and 1 in a patient with angioimmunoblastic T-cell lymphoma) and 1 complete response (in a patient with follicular lymphoma) were noted (overall response rate of 18%) in addition to 9 patients who achieved durable stable disease. Responses were noted predominantly among patients with lymphoma (tumor reduction noted in 63% of patients on standard computed tomography). CONCLUSIONS: The MTD in the current study was found to be 20 mg twice daily. Encouraging and durable activity was observed in patients with Hodgkin lymphoma, T-cell lymphoma, and follicular lymphoma. Cancer 2019;125:99-108.
Cotyledonoid dissecting leiomyoma is a benign smooth muscle neoplasm with an unusual growth pattern that is characterized by intramural dissection within the uterine corpus and often a placental-like appearance macroscopically in its extrauterine component that may be alarming to the surgeon. All cases reported to date have been nonaggressive. We report a case in a 33-yr-old woman who had a history of prolonged uterine bleeding. She was operated upon for uterine leiomyomas, and the diagnosis of cotyledonoid dissecting leiomyoma was made at the time of intraoperative consultation. To maintain fertility, the intrauterine tumor was resected by myomectomy and the extrauterine tumor by excision. However, persistent uterine bleeding that eventually became intractable and continued growth of the neoplasm in the uterus necessitated hysterectomy 5 yr later. She was living and well 2.5 yr after hysterectomy with no evidence of disease.
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