Malnutrition as a prognostic factor in lymphoblastic leukaemia: a multivariate analysis.

One hundred and twenty eight Brazilian children with lymphoblastic leukaemia were intensively treated with a Berlin-Frankfurt-Munich based protocol. More children had a white cell count above 50 x 10(9)/l (31%) then observed in developed countries. After a median follow up of 31 months (11-58 months), the estimated probability of relapse free survival was 41% (7%) for the whole group. After adjustment in the Cox's multivariate model, malnutrition was the most significant adverse factor affecting duration of complete remission. Age above 8 years and high peripheral white cell count were also significant adverse factors. Among the nutritional indices, the height for age and weight for age z scores were both significant, whether the cut off points of z-2 or z = -1.28 were chosen to define malnutrition. A strong statistical association between the two indices was found; the contribution of height for age z score to the prediction of relapse free survival was more significant. Children with height for age z score < -2 had a relapse risk of 8.2 (95% confidence interval 3.1 to 21.9) relative to children with z score > -2. The results of this study suggest that socioeconomic and nutritional factors should be considered in the prognostic evaluation of children with leukaemia in developing countries.

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.

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.

Features affecting outcome during remission induction of acute myeloid leukaemia in 619 adult patients.

Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.