The French-American-British classification of myelodysplastic syndromes

TITLE Proposals for the classification of the myelodysplastic syndromes.

AUTHORS Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C.

JOURNAL British Journal of Haematology 1982;51(2):189-199. PMID: 188440.

In 1976, Dr. John M. Bennett and colleagues, the French-American-British (FAB) cooperative group (Figure 1), published a seminal paper, the first classification of acute myeloid leukemia (AML).¹ Interestingly, for decades it had been recognized that many AML patients experience a preleukemic phase. Rhoads & Barker had reported on 100 patients with "refractory anemia" in 1938.² Several terms were subsequently suggested, including: "preleukemic leukemia", "smoldering leukemia", "preleukemic syndrome (hemopoietic dysplasia)" and "dysmyelopoietic syndrome". The 1976 paper, summarizing data from 150 patients, was the first to distinguish between common AML of recent onset, requiring immediate treatment, and less acute disorders regarded as "preleukemia", with no need for urgent treatment.¹ The authors also noted that many patients with "preleukemia" never evolve to AML and succumb to the complications of bone marrow failure.

Later on, the FAB group realized that further clarifications of the preleukemic phase were required, especially characterization of blasts, and definition of conditions with excess blasts, monocytosis and leukemic progression. Reviewing slides from an additional 80 patients led to the landmark report, changing the field.

The paper introduced the term "myelodysplastic syndrome (MDS)" and proposed guidelines for its diagnosis and classification based on morphological findings, dysplasia and percentage of blasts in the peripheral blood and bone marrow. Five MDS groups were described (Table 1): (i) refractory anemia; (ii) refractory anemia with ring sidero-blasts; (iii) refractory anemia with excess of blasts; (iv) chronic myelomonocytic leukemia (which was included among the MDS, despite controversy); and (v) refractory anemia with excess of blasts 'in transformation' (a new term). A main distinguishing feature of these conditions is the proportion of blast cells in the peripheral blood and/or bone marrow. The morphological features of blasts were redefined and over 30% bone marrow blasts were proposed to diagnose AML.

Figure 1.The French-American-British Leukemia Cooperative Group. Figure provided by Dr. John Bennett, the head of the group. Reproduced with permission.

Table 1.Peripheral blood and bone marrow viariables that the French-American-British cooperative group suggested considering when analyzing a case of myelodysplastic syndrome.

Several aspects made this original report a landmark paper. First, the proposed term, MDS, was new and descriptive but also reflected the biology, i.e., syndromes (not a single disease) of the bone marrow ("myelo"), characterized by defective production (dysplasia). Second, clear guidelines, with some objectivity and quantitation, although arbitrary, for MDS diagnosis were described. The diagnostic criteria are based mainly on peripheral blood and bone marrow morphology, still the backbone of diagnosis even today, despite the developments of novel tools (cytogenetics, immunophenotyping, molecular analysis). Third, this allowed the use of a common language and terminology, providing a platform for research, communication, and permitting comparisons between patients, and led to collaborative clinical trials. Finally, this was an academic collaborative international effort, without external funding.

The MDS FAB guidelines soon became the worldwide gold-standard for the diagnosis and classification of MDS. Numerous publications validated it, leading to more research and clinical trials.³ Not surprisingly, despite new clinical, biological and genetic information that required updated classifications (the World Health Organization classification, Revised International Prognostic Scoring System, Molecular International Prognostic Scoring System), the FAB classification remained the backbone, and all these classifications maintained the structure and philosophy of the FAB proposal.

In summary, the MDS FAB classification manuscript proposed a new term, defined a new disease entity, suggested diagnostic tools and risk stratification and led to a diagnostic, prognostic and therapeutic paradigm change.

Footnotes

Correspondence

*moshemt@gmail.com

Disclosure

No conflicts of interest to disclose.