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K Wheatley

Publications and source records attributed to K Wheatley.

At least 55 records · Page 3Linked to original sources
PubMed1997

Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council.

The relative efficacy and toxicity of the chemotherapeutic agents thioguanine (6TG) and etoposide (VP16) were assessed by a randomized comparison of the DAT (daunorubicin, cytarabine, thioguanine) versus ADE (daunorubicin, cytarabine, etoposide) regimens in the Medical Research Council's 10th acute myeloid leukaemia trial (MRC AML 10), which was open to patient entry from May 1988 to April 1995. In this, the largest reported trial of AML therapy to date, 1,857 eligible patients, mostly less than 56 years old, were randomized: 929 (including 143 children under 15 years old) were allocated to DAT and 928 (143 children) to ADE. The two groups were well matched for presentation features. The complete remission (CR) rate was 81% with DAT and 83% with ADE (P = .3). The percentages of remitters achieving remission after 1, 2, or more than 2 courses were 70%, 22%, and 8% for DAT and 74%, 21%, and 5% for ADE. The percentages failing to achieve a CR due to resistant disease were 11% with DAT versus 9% with ADE (P = .07). There was a slightly higher death rate in CR during consolidation chemotherapy with ADE (9%) than with DAT (6%) (P = .06). Patients receiving DAT took slightly but significantly longer to recover from neutropenia and thrombocytopenia but the median number of days in hospital were similar in each group. ADE patients experienced slightly more severe nonhematologic toxicity. There was also no significant difference between the groups in the longer-term measures of efficacy: disease-free survival at 6 years from CR was 42% (+/-4) for DAT and 43% (+/-4) for ADE (P = .8); relapse rate at 6 years was 50% (+/-4) for DAT and 49% (+/-5) for ADE (P = .6); survival at 6 years was 40% (+/-4) for both DAT and ADE (P = .9). Subgroup analysis failed to show any benefit for etoposide in patients with monocytic or myelomonocytic disease, or in any other diagnostic subgroup. In conclusion, DAT and ADE both achieve high remission rates and good long-term survival, and are equally effective chemotherapy regimens for the treatment of AML patients aged up to 55 years.

Acute Disease↗
PubMed1997

What happens subsequently in AML when cytogenetic abnormalities persist at bone marrow harvest? Results of the 10th UK MRC AML trial. Medical Research Council Leukaemia Working Parties.

Cytogenetic analysis performed at diagnosis is widely recognised to provide one of the most valuable prognostic indicators in AML. Yet any role for this technique in residual disease assessment, particularly in the context of subsequent transplantation procedures has been incompletely explored. The present study considers the outcome of 190 patients drawn from the UK MRC AML 10 trial in whom cytogenetics were assessed whilst in morphological CR at the time of bone marrow harvest. Cytogenetics at this stage were abnormal in 19 patients (10%). In 11/19 patients, the abnormalities detected reflected the acquisition of new clonal (3/11) or nonclonal changes (8/11) that were not identified at diagnosis; comparison of this group to patients with normal cytogenetics at harvest provided no evidence that such acquired changes are of prognostic significance. In 8/19 patients, abnormalities detected were indicative of persistence of the disease-related clone in harvested marrow. Two of these patients died of sepsis during consolidation therapy. Two received ABMT in first morphological CR: one patient with AML associated with a favourable karyotype (+8,inv(16)) remains in CR, 5.5 years post-transplant, whereas the other with cytogenetic abnormalities considered to confer a poor prognosis (inv(3q),-7), relapsed within 5 months of ABMT. All four of the remaining patients with cytogenetic evidence of persistent disease who were not transplanted in first CR, relapsed within 6.5 months of harvest. Therefore, among 101 of 190 patients with AML characterised by abnormal karyotype at diagnosis, persistence of the disease-related clone in eight patients (8%), revealed by conventional cytogenetic assessment at bone marrow harvest whilst in morphological remission, was found to predict a poor prognosis. Nevertheless, transplantation procedures using marrow which is obviously contaminated with the original leukaemic clone may occasionally still be associated with long-term survival.

Adolescent↗
PubMed1997

Incidence of AML1/ETO fusion transcripts in patients entered into the MRC AML trials. MRC Adult Leukaemia Working Party.

Acute myeloid leukaemia (AML) with the t(8;21)(q22;q22) is deemed to be a 'good-risk' disease. 396 patients with AML at diagnosis were screened for the presence of t(8;21) and AML1/ETO fusion transcripts by cytogenetic and RT-PCR techniques respectively. 32 cases of t(8;21) were detected, all of which were also PCR positive. A further 19 cases were detected at the molecular level, predominantly but not exclusively in M1 and M2 FAB types. Approximately 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type.

Acute Disease↗
PubMed1997

Frequency of CBF beta/MYH11 fusion transcripts in patients entered into the U.K. MRC AML trials. The MRC Adult Leukaemia Working Party.

It has been established that cytogenetic findings at diagnosis of acute myeloid leukaemia (AML) are a powerful prognostic indicator. Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo. are deemed to have good-risk disease. This subtle translocation may be difficult to detect in poor-quality metaphase preparations and if missed could lead to the incorrect assignment of risk group and influence further treatment strategies. We studied 321 patients with AML at diagnosis for the presence of inv(16)(p13q22) and CBF beta/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respectively. Karyotypic analysis detected 21 cases of inv(16) (p13q22), all of which were PCR positive. A further 12 cases were detected at the molecular level only, in FAB types other than M4Eo. The observed frequencies of CBF beta/MYH11 fusion transcripts in our study have been adjusted for the reported incidence of each FAB subtype and we calculate that 10.1% of all new cases of AMLs have molecular evidence of inv(16)(p13q22). only half of which are of the M4Eo subtype. We conclude that molecular screening for the presence of CBF beta/MYH11 fusion transcripts should be mandatory in all case of AML at diagnosis.

Adolescent↗
PubMed1996

Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34 overexpression in acute myelogenous leukemia M2 with t(8;21).

During the immunodiagnosis of 517 cases of acute myelogenous leukemia (AML) entered into the Medical Research Council (MRC) AML 10 trials, we have observed the CD34 precursor cell antigen more frequently in AML of M2 morphology, especially in the 84% of cases with the t(8;21) chromosomal translocation, than in any other French-American-British classification group. CD34 expression was then quantified (using QIFI and Quantum Simply Cellular beads [Flow Cytometry Standards, Research Triangle Park, NC] and CD34+ standard cells). When CD34 antibody-binding capacity (ABC) of normal bone marrow (BM) precursors and leukemic blasts was compared, it was shown that AML M2 cases with t(8;21) not only had the highest percentages of CD34+ blasts, but in > 80% of CD34+ cases the individual blasts expressed higher than normal levels of CD34 antigen (> 60 x 10(3) ABC per cell). In addition, in 73% of this group CD34 antigen was overexpressed in an asynchronous combination with cytoplasmic myeloperoxidase (MPO). Other signs of asynchrony included high CD34 expression with CD15 and/or CD56, as well as aberrant combinations of CD13 with terminal deoxynucleotidyl transferase (TdT) and CD19. These findings demonstrate that asynchrony is identifiable in virtually every case of AML with t(8;21), although it does not always involve the same antigens. M2 cases with t(8;21), mostly CD34+, had a 100% remission rate and 71% 5-year survival rate; other patients with CD34+ or CD34- AML showed 69% and 84% remission rates and 31% and 36% 5-year survival rates, respectively. Consequently, individual markers such as CD34 should be interpreted in relation to other features such as chromosomal changes. These simple methods, which are well suited to quantify the expression of ligands, are a useful contribution to diagnosis: 60% to 65% of M2 cases with t(8;21) are rapidly identified by CD34 overexpression alone. This aberration, together with the other signs of asynchrony seen at presentation, can be used to search for residual leukemia after therapy.

Adolescent↗
PubMed1996

A modular questionnaire for the assessment of longterm quality of life in leukaemia patients: the MRC/EORTC QLQ-LEU.

We describe the psychometric analysis of a supplementary quality of life measure (MRC/EORTC QLQ-LEU) for evaluating long term sequelae of leukaemia treatments. The questionnaire under development was administered to 388 patients entered into the EORTC-GIMEMA AML 8A and the MRC AML10 clinical trials who were in complete remission for at least one year after completion of treatment on these trials. Results indicated a measure which is useful in evaluating the long-term effects of treatment in relation to chronic graft-vs-host disease and infection susceptibility. The performance of this measure in terms of its sensitivity and specificity between treatment arms was established by comparisons between the three treatment modalities in the above-mentioned trials and is the subject of further investigation. The new Leukaemia Module can be recommended for use alongside generic QOL instruments as a measure of long-term quality of life in leukaemia trials.

Acute Disease↗
PubMed1996

Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

Adolescent↗
PubMed1996

The retinoblastoma gene (rb1) in acute myeloid leukaemia: analysis of gene rearrangements, protein expression and comparison of disease outcome.

The occurrence of retinoblastoma gene abnormalities in a large subset of various malignancies suggests an important role for this tumour suppressor gene in carcinogenesis, but this varies considerably from one tumour type to another and results in patients with acute myeloid leukaemia (AML) have been controversial. We analysed 106 AML patients and 18 normal controls for RB1 gene rearrangements and 86 AML patients for RB protein (pRB) expression. Southern blot analysis detected no gross gene rearrangements, but several restriction enzyme polymorphisms were observed. By Western blot analysis, 20 patients (23%) had no detectable pRB protein and seven (8%) had truncated pRB bands. Discordance between the DNA and protein data suggests that there may be minor deletions and point mutations in the RB1 gene or abnormalities in the proteins regulating the expression of pRB. No significant differences in the frequency of attainment of complete remission or length of survival were observed between patients with normal and abnormal pRB.

Acute Disease↗
PubMed1996

Establishing the presence of the t(15;17) in suspected acute promyelocytic leukaemia: cytogenetic, molecular and PML immunofluorescence assessment of patients entered into the M.R.C. ATRA trial. M.R.C. Adult Leukaemia Working Party.

Detection of the t(15;17) or its molecular consequence, the PML-RAR alpha rearrangement, is critical for meaningful analysis of clinical trials involving patients with suspected acute promyelocytic leukaemia (APL). Its presence remains the best predictor of a favourable response to retinoids, such as ATRA, which in combination with chemotherapy confer significant improvements in disease-free survival. We have evaluated the relative efficacy of RT-PCR, cytogenetics and PML immunofluorescence staining to identify the existence of the translocation in 100 patients entered into the Medical Research Council (M.R.C.) ATRA trial. RT-PCR successfully identified PML-RAR alpha rearrangements in 93/100 patients, including 65 where only peripheral blood or post-induction marrow samples were available for analysis and in 12 patients in whom cytogenetic assessment failed to demonstrate t(15;17) due to poor-quality metaphases (10/12) or as a reflection of cryptic PML-RAR alpha rearrangements (2/12). Parallel employment of the RAR alpha-PML assay confirmed expression of del(17q)-derived transcripts in 81% and permitted determination of the PML breakpoint (a potential independent prognostic variable) in all 93 cases. Sequencing of RT-PCR products derived from 50 patients with 3' PML breakpoints revealed five bcr 2 cases, including a novel exon 5 breakpoint. 35/81 (43%) patients with cytogenetic evidence of t(15;17) possessed additional karyotypic abnormalities. In four patients with available buffy coat smears, lack of cytogenetic or molecular evidence of the t(15;17) was confirmed by a wild-type PML immunofluorescence nuclear staining pattern, in contrast to the characteristic microparticulate distribution detected in 14 patients with RT-PCR evidence of the rearrangement. However, although PML immunofluorescence staining is suitable for rapid determination of patients likely to benefit from ATRA, this approach does not obviate the need for cytogenetic and RT-PCR analysis of all patients entered into APL clinical trials, because both techniques provide additional information which may prove to be of independent prognostic significance.

Adolescent↗
PubMed1995

Bcl-2 protein expression in normal human bone marrow precursors and in acute myelogenous leukemia.

The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.

Antigens, CD↗
PubMed1994

Mortality in relation to smoking: 40 years' observations on male British doctors.

OBJECTIVE: To assess the hazards associated with long term use of tobacco. DESIGN: Prospective study of mortality in relation to smoking habits assessed in 1951 and again from time to time thereafter, with causes sought of deaths over 40 years (to 1991). Continuation of a study that was last reported after 20 years' follow up (1951-71). SUBJECTS: 34,439 British male doctors who replied to a postal questionnaire in 1951, of whom 10,000 had died during the first 20 years and another 10,000 have died during the second 20 years. RESULTS: Excess mortality associated with smoking was about twice as extreme during the second half of the study as it had been during the first half. The death rate ratios during 1971-91 (comparing continuing cigarette smokers with life-long non-smokers) were approximately threefold at ages 45-64 and twofold at ages 65-84. The excess mortality was chiefly from diseases that can be caused by smoking. Positive associations with smoking were confirmed for death from cancers of the mouth, oesophagus, pharynx, larynx, lung, pancreas, and bladder; from chronic obstructive pulmonary disease and other respiratory diseases; from vascular diseases; from peptic ulcer; and (perhaps because of confounding by personality and alcohol use) from cirrhosis, suicide, and poisoning. A negative association was confirmed with death from Parkinson's disease. Those who stopped smoking before middle age subsequently avoided almost all of the excess risk that they would otherwise have suffered, but even those who stopped smoking in middle age were subsequently at substantially less risk than those who continued to smoke. CONCLUSION: Results from the first 20 years of this study, and of other studies at that time, substantially underestimated the hazards of long term use of tobacco. It now seems that about half of all regular cigarette smokers will eventually be killed by their habit.

Adult↗
PubMed1994

Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors.

OBJECTIVE: To assess the risk of death associated with various patterns of alcohol consumption. DESIGN: Prospective study of mortality in relation to alcohol drinking habits in 1978, with causes of death sought over the next 13 years (to 1991). SUBJECTS: 12,321 British male doctors born between 1900 and 1930 (mean 1916) who replied to a postal questionnaire in 1978. Those written to in 1978 were the survivors of a long running prospective study of the effects of smoking that had begun in 1951 and was still continuing. RESULTS: Men were divided on the basis of their response to the 1978 questionnaire into two groups according to whether or not they had ever had any type of vascular disease, diabetes, or "life threatening disease" and into seven groups according to the amount of alcohol they drank. By 1991 almost a third had died. All statistical analyses of mortality were standardised for age, calendar year, and smoking habit. There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk; those who reported drinking 8-14 units of alcohol a week (corresponding to an average of one to two units a day) had the lowest risks. The causes of death were grouped into three main categories: "alcohol augmented" causes (6% of all deaths: cirrhosis, liver cancer, upper aerodigestive (mouth, oesophagus, larynx, and pharynx) cancer, alcoholism, poisoning, or injury), ischaemic heart disease (33% of all deaths), and other causes. The few deaths from alcohol augmented causes showed, at least among regular drinkers, a progressive trend, with the risk increasing with dose. In contrast, the many deaths from ischaemic heart disease showed no significant trend among regular drinkers, but there were significantly lower rates in regular drinkers than in non-drinkers. The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality. Similar differences persisted irrespective of a history of previous disease, age (under 75 or 75 and older), and period of follow up (first five and last eight years). Some, but apparently not much, of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers. CONCLUSION: The consumption of alcohol appeared to reduce the risk of ischaemic heart disease, largely irrespective of amount. Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week. Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol, or the consumption of substantial amounts. Above about three units (two American units) of alcohol a day, progressively greater levels of consumption are associated with progressively higher all cause mortality.

Adult↗
PubMed1992

Intensive chemotherapy with or without additional bone marrow transplantation in paediatric AML: progress report on the MRC AML 10 trial. Medical Research Council Working Party on Childhood Leukaemia.

The Medical Research Council's AML 10 Children Trial commenced in 1988. It is a multicentre collaborative study based on 4 courses of intensive chemotherapy with additional allogeneic bone marrow transplantation for children with a matched sibling donor. The remaining children are randomised either to an autologous transplant using unpurged marrow or stopping therapy. To date 156 eligible patients have been entered with a CR rate of 91%. 56% of children are still alive 2 years after trial entry and 57% are in CR 3 years after achieving CR. The treatment regimen is intensive but mortality and morbidity are acceptable. The study will need to accrue patients for a further 2 to 3 years in the hope of defining the role of allogeneic and autologous marrow transplantation.

Acute Disease↗
PubMed1991

Prognostic importance of Sudan Black positivity: a study of bone marrow slides from 1,386 patients with de novo acute myeloid leukaemia.

Analysis of bone marrow slides from 1,386 patients entered into the Medical Research Council's 8th and 9th trials in Acute Myeloid Leukaemia confirmed that features associated with differentiation in blast cells, in particular increasing Sudan Black (SB) positivity, were the most important morphological features for predicting remission achievement (P = 0.002) and hence survival (P less than 0.0001). SB positivity was also weakly predictive of remission duration (P = 0.05). A low complement of maturing granulocytes was associated with early induction death and a high percentage of blasts with shorter remissions. The few patients with acute promyelocytic leukaemia (FAB M3) had a high haemorrhagic death rate during induction and a low relapse rate. Apart from this, lineage involvement was not predictive of outcome. Multiple lineage leukaemias, in particular those with megakaryocytic and/or erythroid involvement, which had been reported previously to have a poor prognosis, did not have any worse remission rates in this series. When more than one cell line was involved, no combination with particularly good or poor prognosis could be identified. Multivariate analysis suggested that percentage SB positivity was adequate on its own to divide granulocytic leukaemias into poorly differentiated (less than 50% SB +ve) and well-differentiated groups (50% or more SB +ve) without the need for further measurements. This simple and reproducible test was strongly predictive of resistant disease but not of induction deaths. It was of considerably greater prognostic value--and was less open to inter-observer disagreement--than the FAB criteria which are usually used to classify granulocytic lineage leukaemias into the M1 and M2 subgroups. It is proposed that greater than or equal to 50% of blasts with SB positivity should replace blasts greater than 10% of maturing myeloid cells for this sub-categorization between M1 and M2.

Acute Disease↗
PubMed1991

How to avoid bias when comparing bone marrow transplantation with chemotherapy.

It is important to know whether the survival of patients receiving an allogeneic bone marrow transplant (BMT) is better than that of patients receiving "conventional" treatment and, if BMT is better, to know how much better. Unfortunately, this information is surprisingly difficult to obtain accurately. Most studies that have attempted to define the value of BMT have been subject to varying degrees of bias because of the problems of identifying a "conventional chemotherapy" control group with which the outcome of patients who have received BMTs can be compared. A common bias arises when disease-free survival of BMT patients is compared with that of all other remitters. Early failures are then automatically assigned to the chemotherapy group even if they have donors and so would have gone on to a BMT had they not relapsed or died. Since some patients receive BMTs many months (or even years) after achieving remission-when their prognosis is already much improved-the definition of "early failure" is problematic. Nevertheless, although it is very rarely used, an adequate statistical method does exist to overcome this problem. Careful analysis cannot, however, overcome the problem of selection bias: patients selected for BMT are likely to have better (or worse) prognosis than patients who are treated conventionally. The only really satisfactory way of assessing the value of BMT is to conduct randomised trials comparing BMT with no BMT - or with extra chemotherapy. Several such studies are currently being undertaken assessing the role of autologous BMT in AML.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1989

AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial.

The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelodysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow. The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P = 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P = 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases. Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (greater than 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P = 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement. Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of these were in Group 1.

Adolescent↗
PubMed1989

The significance of ultrastructural features in acute myeloid leukemia: a study of 220 patients entered into the Medical Research Council's ninth acute myeloid leukemia trial.

Samples of peripheral blood or bone marrow obtained before treatment from 220 patients entered into the Medical Research Council's ninth acute myeloid leukemia (AML) trial were examined by electron microscopy. Several ultrastructural features showed strong correlations with each other, with variants of AML defined by the Hayhoe classification scheme, and with FAB type. However, no ultrastructural feature was found either uniquely in association with any other or specifically in any variant of AML. Each ultrastructural feature was tested for association with achievement of remission, remission duration, and survival time. Only Auer rods were associated with a high remission rate (p = 0.01), but even this association was not quite conventionally significant when the analysis was not quite conventionally significant when the analysis was stratified for age (p = 0.055). Shorter duration of remission was associated with cytoplasmic projections (p = 0.04 stratified for age). Overall survival was worse when convoluted or lobed nuclei were present but only when stratified for age and Hayhoe type (p = 0.04). The possibility of testing combinations of ultrastructural features for correlation with diagnosis or prognosis is discussed but would require data from more than the present 220 patients to be meaningful.

Bone Marrow↗