The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997.

INTRODUCTION Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC)) of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November, 1997, to discuss clinical issues related to the classification. RESULTS The WHO has adopted the 'Revised European American Classification of Lymphoid Neoplasms' (R.E.A.L.), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO Classification has applied the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). CONCLUSION The experience of developing the WHO Classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

[1]  V. Diehl,et al.  Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure? , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  P. Mclaughlin,et al.  Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  B. Coiffier,et al.  Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte. , 1993, The New England journal of medicine.

[4]  J. Armitage,et al.  A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. , 1998, The New England journal of medicine.

[5]  A. Hagenbeek,et al.  Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. , 1995, The New England journal of medicine.

[6]  H Tesch,et al.  BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  S. Hancock,et al.  Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  N. Ueno,et al.  Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  B. Cheson,et al.  Report of an international working group to standardize response criteria for myelodysplastic syndromes. , 2000, Blood.

[10]  J. Gribben,et al.  High-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation in mantle-cell lymphoma: no evidence for long-term remission. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  H. Kantarjian,et al.  Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  J. Hainsworth,et al.  Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. , 2000, Blood.

[13]  R. Levy,et al.  Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[15]  L. Gordon,et al.  Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[17]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[18]  A. Norton,et al.  Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  T M Grogan,et al.  Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. , 1993, The New England journal of medicine.

[20]  L. Gordon,et al.  Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  T. Lister,et al.  Follicular lymphoma: prognostic factors for response and survival. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  J. Armitage,et al.  International Consensus Conference on High-Dose Therapy with Hematopoietic Stem Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas: report of the jury. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  V. Diehl,et al.  Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  B. Coiffier,et al.  Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  W. Chan,et al.  Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  D. Weisenburger,et al.  New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  A. Nagler,et al.  Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. , 1998, Blood.

[28]  J. Gribben,et al.  Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. , 1999, Blood.

[29]  R B Mann,et al.  Criteria for the cytologic subclassification of follicular lymphomas: A Proposed alternative method , 2007, Hematological oncology.

[30]  R. Fisher,et al.  Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  M. Grever,et al.  Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies. , 2000, Blood.