C. Sultan

Proposals for the Classification of the Acute Leukaemias French-American-British (FAB) Co-operative Group

Summary. A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell‐surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone‐marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia,‘lymphoblastic’and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.

Proposals for the classification of the myelodysplastic syndromes

Summary. New, diagnostic criteria for the diagnosis of the various myelodysplastic syndromes (MDS) are proposed, and a detailed description is given of the features that may help define MDS. Five MDS are described: (1) refractory anaemia (RA), (2) RA with ring sideroblasts, (3) RA with excess of blasts (RAEB), (4) chronic myelomonocytic leukaemia (CMML), and (5) RAEB ‘in transformation’. One of the main distinguishing features of these conditions is the proportion of blast cells in the peripheral blood (PB) and/or bone marrow (BM). The morphological features of the blast cells that are of diagnostic importance have been redefined. In RA, with or without ringed sideroblasts, there are fewer than 1% of blasts in the PB and fewer than 5% in the BM; RAEB is defined as having between 5% and 20% of blasts in the BM and fewer than 5% in the PB; RAEB in transformation (a newly defined category) will be considered when any one of the following features is present: (i) more than 5% of blasts in the PB, (ii) 20‐30% in the BM, and (iii) the presence of Auer rods in granulocyte precursors in BM or PB. In accordance with these newly defined criteria, it is now proposed that over 30% of bone marrow blasts will suffice for the diagnosis of acute myeloid leukaemia (AML) in any of its forms (M1‐M6). The proposed descriptions of the MDS should facilitate the interpretation of data emerging from cytogenetic and bone marrow culture studies and the search for features of possible prognostic significance. Recognition of the new category, RAEB in transformation, may throw light on the pathogenesis of AML.

Proposed Revised Criteria for the Classification of Acute Myeloid Leukemia: A Report of the French-American-British Cooperative Group

Excerpt The first proposals for the morphologic classification of the acute leukemias by the French-American-British (FAB) group (1) were put forward in the hope that they might serve as a basis fo...

Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO)

Summary. We describe a form of acute myeloid leukaemia (AML), designated AML‐MO, with minimal myeloid differentiation, not included previously in the FAB classification. AML‐MO cannot be diagnosed on morphological grounds alone as the blast cells are large and agranular, sometimes resembling L2 or, rarely, L1 lymphoblasts, and should be identified by the following features: negative myeloperoxidase (MPO) and Sudan Black B reaction (or positive in less than 3% of blasts), negative B and T lineage markers and expression of myeloid antigens recognized by at least one monoclonal antibody, CD13 or CD33. Other myeloid markers are also often positive and these include CDllb and the enzyme MPO demonstrated by immunocytochemistry and or electron microscopy analysis. The findings in a group of 10 cases satisfying the criteria for AML‐MO are described. AML‐MO represents 2–3% of all cases of AML and 1–1·5% of all acute leukaemias. Its clinical and biological significance is not yet apparent but its identification in a larger number of cases may achieve this aim.

Criteria for the Diagnosis of Acute Leukemia of Megakaryocyte Lineage (M7): A Report of the French-American-British Cooperative Group

For the diagnosis of M7, the bone marrow aspirate shows a leukemic cell infiltrate that comprises 30% or more of all cells. These cells are identified as being of megakaryocyte lineage by the platelet peroxidase reaction on electron microscopy or by tests with monoclonal or polyclonal platelet-specific antibodies. Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7. In patients with increased reticulin, the bone marrow sample may be difficult to obtain and the counts done on the marrow films may be misleading. In these patients, the diagnosis of M7 should be based on excellent bone marrow biopsy sections that show an excess of blasts and, at times, increased numbers of maturing megakaryocytes; and on the presence of unequivocal megakaryoblasts in the peripheral blood or bone marrow (or both) as shown by immunologic techniques.

Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.

Peripheral blood, bone marrow films, and bone marrow biopsy specimens from 110 patients, well characterised by clinical and laboratory studies, including electron microscopy, were reviewed, to determine proposals for the classification of chronic (mature) B and T cell leukaemias. On the basis of cytology and membrane phenotype the following disorders were defined: (i) B cell type: chronic lymphocytic leukaemia (CLL); CLL of mixed cell type, which includes cases with more than 10% and less than 55% prolymphocytes (CLL/PL), and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukaemia (PLL); hairy cell leukaemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes; leukaemic phase of non-Hodgkins lymphoma (follicular lymphoma, intermediate, or mantle zone lymphoma and others); lymphoplasmacytic lymphoma with peripheral blood disease (mostly Waldenströms macroglobulinaemia); and plasma cell leukaemia. (ii) T cell type: T/CLL, which was differentiated from reactive T/lymphocytosis; T/PLL; adult T cell leukaemia/lymphoma; and Sézarys syndrome. The recognition of distinct entities within the B and T cell leukaemias seems to have clinical and epidemiological connotations. It is hoped that these proposals may serve as the basis for further work, discussion, and improved management of patients.

The Morphological Classification of Acute Lymphoblastic Leukaemia: Concordance among Observers and Clinical Correlations

Summary. The degree of concordance in the morphological classification of ALL was assessed by the FAB group after two successive reviews of 200 and 100 slides respectively. As a result, a simple scoring system for types L1 and L2 is proposed based on the following four features: (1) nuclear cytoplasmic ratio, (2) presence, prominence and frequency of nucleoli, (3) regularity of nuclear membrane outline, and (4) cell size. By this method, the overall concordance by seven observers (agreement of 7:0 or 6:1 only) increased from 63% to 84%.

The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group.

Summary. We have reviewed our experience with four of the entities that are included under the generic term chronic myeloid leukaemia (CML), namely the classic Ph+ CGL, both BCR+ and BCR−, aCML and CMML. We have developed a statstical model that confirms that CGL, aCML and CMML can be distinguished from each other with reasonable success employing five quantitative parameters (WBC, percentage immature granulocytes, percentage monocytes, percentage basophils, percentage erythroid precursors in bone marrow) and one qualitative parameter (granulocytic dysplasia). It is hoped that these detailed recommendations will enable investigators to improve their diagnostic accuracy. This should permit more uniform comparisons of molecular biologic and clinical studies.

Classification of Acute Leukemia

Abstract The classification of acute leukemia has almost invariably been based on the morphologic diagnosis into two broad categories: acute lymphocytic and acute myeloid leukemia. Despite the wide...

ACUTE PROMYELOCYTIC LEUKAEMIA: HAEMORRHAGIC MANIFESTATION AND MORPHOLOGIC CRITERIA

Haeniorrhage is the second most common fatal complication in patients with acute leukaemia. These haemorrhagic complications were initially attributed either to a quantitative or qualitative platelet abnormality; however, subsequent studies revealed that quantitative platelet defects wcrc responsible for the majority of mucocutaneous and intracerebral haemorrhages in patients with acute leukaemia. Platelet transfusion therapy has reduced the risk of haemorrhage in these patients during periods of thrombocytopenia due to bone marrow replacement or bone marrow hypoplasia. The technique of HL-A typing and the use of HL-A matched platelets have resulted in the ability to provide long-term platelet support to these patients and further reduce the incidence of haemorrhage. Despite the decrease in haemorrhage due to thrombocytopenia, bleeding and thrombosis are still a relatively common finding in patients with acute leukaemia. Investigation of the syndrome of intravascular coagulation in man has revealed a complex constellation of coagulation and fibrinolytic abnormalities. Recognition of this syndrome in patients with leukaemia or other malignancies is hampered by the high levels of coagulation factors commonly present in these patients and the effects of chemotherapy, hepatic dysfunction and infection on coagulation tests. Despite these difficulties, intravascular coagulation has been recognized with increasing frequency in malignant diseases (Merskey et al, 1967; Brain et al , 1970; Colman et al, 1972; Lohrmann et a!, 1973). Acute proinyelocytic leukaemia (APL), a unique form of acute myeloblastic leukaemia (AML), is constantly associated in our experience with intravascular coagulation. Studies of this disease have increased our understanding of the role of the neoplastic cell in the initiation of haemorrhagic and/or thrombotic diatheses. Hillstad, in 1957, first described the clinical entity of APL. He found three patients with the triad of a leukaemic blood picture composed primarily of proniyelocytes, hypofibrinogenaemia and marked haemori1ia:ge. Didisheiin et al (1964) dcscribed factor-V deficiency in addition to hypofibrinogcnaernia and thrombocytopenia in two patients with APL. Baker et al (1967) described a patient with APL with the clinical and laboratory findings of intravascular coagulation. Trcatmcnt of this patient with heparin resulted in complete correction of the clinical bleeding and haemostaitic abnormalities. Approximately 13 5 cases of APL havc been described in thc literature. In general these reports support the concept that APL is a unique form of leukaemia manif’cst by massive haemorrhage and hypofibrinogenaemia, a distinct morphologic picture and a rapidly fatal course. The pathogenesis of the hypofibrinogenaeniia and bleeding has generally been attributed to intravascular coagulation, although some controversy still exists (Nilsson et al , 1960; Rand et al, 1969; Straub & Frick, 1970). Clinically these patients almost invariably present with symptoms of liacmorrhage. The haemorrhagic manifestations usually include petechiae, small ecchymoses, haematuria,