F. G. J. Hayhoe

8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features

Summary. Thirty patients with the 8;21 translocation and three with closely related variants have been studied. Ages ranged from 3 to 64 years (mean 28±3). Thirty‐one were entered into the MRCs 8th Acute Myeloid Leukaemia Trial. Twenty‐nine (88%) achieved complete remission. Marrow smears from most patients showed granulocytic maturation (M2, FAB classification) with characteristic abnormalities, but at least six showed predominantly myeloblastic (M1) morphology. The blast cells were markedly heterogeneous with regard to size and nuclear cytoplasmic ratio. Typical staining patterns were observed in the blast cells using Sudan black B and diaminobenzidine peroxidase stains, and to a lesser extent with periodic acid‐Schiff and chloroacetate esterase. Butyrate esterase was negative in all cases. Auer rods were present in the granulocyte precursors in 31 cases and in eosinophil precursors in two cases. In most cases the existence of the translocation was predicted from the cytological and cytochemical findings. Seven patients developed solid leukaemic deposits, principally in the mastoid cavities, orbital cavities or thoracic spine (extradural).

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

Summary. The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelo‐dysplastic 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.

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

Summary. Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Councils eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematologi‐cal 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 × 109/1. 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 morphologïcal and cytoche‐mical 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 13 3 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.

Beneficial effect of heparin in the management of patients with APL.

Summary 115 patients with acute promyelocytic leukaemia (APL) were studied retrospectively to evaluate prognostic factors and assess therapeutic approaches, particularly the use of heparin in the management of disseminated intravascular coagulation (DIC). The remission rate was 86% (30/35 patients) in those who received heparin and 49% (39/80 patients) in those who received no heparin (P= 0.0002). This difference in remission rates was accounted for by a marked decrease in the number of haemorrhagic deaths, especially those due to intracranial haemorrhage (ICH), in the heparin treated group. Other factors associated with a poor remission rate were prothrombin ratio (PTR) > 1.3 (P=0.008), fibri‐nogen < 1.5 g/l (P=0.02) and WCC >2.0x109/1 (P=0.03).

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 1386 patients entered into the Medical Research Councils 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<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 (<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 ≥ 50% of blasts with SB positivity should replace blasts > 10% of maturing myeloid cells for this sub‐categorization between Ml and M2.

Two further cases of acute myeloid leukemia with trisomy 4

Two cases of acute myeloid leukemia (FAB M1 and M2) with trisomy 4 are described. Morphologic abnormalities were confined to the granulocytic monocytic lineage with no evidence of erythroid or megakaryocytic involvement. One of the cases, who also had trisomy 13, presented initially with skin infiltration without bone marrow involvement.

Translocation (3;6)(q21;p21) in acute myeloid leukemia with abnormal thrombopoiesis and basophilia

A case of acute myeloid leukemia (AML) with increased numbers of basophils and abnormal megakaryocytes was shown to have a t(3;6)(q21;p21) in the bone marrow cells. The morphology is described in detail and the case is discussed with reference to t(6;9)(p23;q34) and inv/ins(3)(q21q26) in AML. It is possible that increased numbers of basophils in AML may be associated with a translocation involving 6p21-6p23.

Complex translocation t(8;12;14) in a cell line derived from a child with nonendemic Burkitt-type acute lymphoblastic leukemia

A cell line is described with a typical Burkitt lymphoma (BL) marker 14q+ due to the classical reciprocal translocation between chromosome #8 and #14 with breakpoints at 8q24.1 and 14q32.3. In addition, an interstitial piece from the long arm of 12(q24.1-q24.3) is inserted at the site of the exchange on chromosome #8, proximal to 14q32.3.

CYTOLOGICAL FEATURES OF 9q‐ DELETIONS IN AML

Interstitial deletions of the long arm of chromosome 9 (9q -) have been reported in haematological malignancies usually in association with other chromosome abnormalities, particularly the 8:2 1 translocation (Mecucci et al, 1984: Kao et aJ, 1986), and here the cytological features characteristic of that translocation (Swirsky et aJ, 1984) generally predominate. Five cases have been reported with 9qas the sole chromosomal anomaly at diagnosis, three of whom had AML. We describe five further cases of de novo AML with 9q (q13q22) as the only cytogenetic anomaly. All five cases had similar cytological and cytochemical features. Cytogenetics were performed at diagnosis except for one patient who was studied at relapse. There were no specific clinical features deserving comment, and the patients ranged in age from 36 to 66 years. The main morphological features were the marked variation in size and N/C ratio in the blasts, the preponderance of agranular blasts, many of which had a reticulated appearance to the cytoplasm on Romanowsky stains {Fig l), and the presence of moderately common Auer rods, vacuoles or other inclusions on both Romanowsky and Sudan black stains. The majority of blasts were Sudan black positive showing typically the presence of large hollow granules (Fig 2) which we speculate may represent intermediate stages in Auer rod formation since the Auer rods were often short, squat and sometimes appeared hollow, with sudanophobic centres. PAS staining of the blasts varied from negative to weak Muse positive, butyrate esterase was consistently negative and chloroacetate esterase was positive in all cases, in 1-35% of blasts. Mature myeloid cells were markedly reduced but the majority of neutrophils showed normal granularity as did eosinophils. The red cell series in all cases showed variable degrees of dyserythropoiesis. with nuclear fragmentation, binucleate cells and nuclear cytoplasmic asynchrony. Two Groffen. J.. Stephenson, J.R.. Heisterkamp. N., de Klein. A.. Bartram. C.R. & Grosveld. G. (1984) Philadelphia chromosomal breakpoints are clustered within a limited region, bcr. on chromosome 22. Cell.

Translocation 5;21 and interstitial deletion of chromosome 7 in a case of chronic myelomonocytic leukemia

We report a case of chronic myelomonocytic leukemia with a translocation involving chromosome 5 and 21, namely, t(5;21)(q35.3;q22.1), and an interstitial deletion of the long arm of chromosome 7. High-resolution analysis at the 900-band stage has shown that the lesion in chromosome 7 is an interstitial deletion involving loss of the segments q22-q35 of the long arm of chromosome 7 and retaining the telomere.