Acquired disorders of the bone marrow
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Bone marrow disorders may either be congenital or acquired. Only acquired bone disorders are discussed below. Bone marrow disorders may be myelosuppression, myeloproliferation, or mixed/unclassified (features of both).
Classification
Acquired bone marrow disorders include:
- Bone marrow suppression: Reduced numbers of cells in bone marrow
- Bone marrow proliferation: Increased numbers of cells in bone marrow
- Mixed or Unclassified: Difficult to classify as suppression or proliferation at diagnosis or disorder that contains features of both.
Shown below is an algorithm that depicts the classification of acquired bone marrow disorders.
| Myelodysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||
| All hematopoietic lineages | Aplastic anemia (aplastic pancytopenia) | ||||||||||||||||||||||||||||||||||||||||||||||||
| Paroxysmal nocturnal hemoglobinuria (PNH) | |||||||||||||||||||||||||||||||||||||||||||||||||
| Myelosuppressive disorders | |||||||||||||||||||||||||||||||||||||||||||||||||
| Pure red cell aplasia (erythroblastopenia) | |||||||||||||||||||||||||||||||||||||||||||||||||
| One lineage | Neutropenia (granulocytopenia and agranulocytosis | ||||||||||||||||||||||||||||||||||||||||||||||||
| Bone marrow suppression | |||||||||||||||||||||||||||||||||||||||||||||||||
| Amegakaryocytic thrombocytopenia | |||||||||||||||||||||||||||||||||||||||||||||||||
| T-cell immunosuppression | |||||||||||||||||||||||||||||||||||||||||||||||||
| Immunosuppression | |||||||||||||||||||||||||||||||||||||||||||||||||
| B-cell immunosuppression | |||||||||||||||||||||||||||||||||||||||||||||||||
| Polycythemia vera | |||||||||||||||||||||||||||||||||||||||||||||||||
| Essential thrombocytopenia | |||||||||||||||||||||||||||||||||||||||||||||||||
| Myeloproliferative disorders | Primary myelofibrosis | ||||||||||||||||||||||||||||||||||||||||||||||||
| Systemic mastocytosis | |||||||||||||||||||||||||||||||||||||||||||||||||
| Acquired bone marrow disorders | Bone marrow proliferation | ||||||||||||||||||||||||||||||||||||||||||||||||
| Chronic myeloid leukemia (CML) | |||||||||||||||||||||||||||||||||||||||||||||||||
| T-cell lymphoproliferative disorder | |||||||||||||||||||||||||||||||||||||||||||||||||
| Immunoproliferation | |||||||||||||||||||||||||||||||||||||||||||||||||
| B-cell lymphoproliferative disorder | |||||||||||||||||||||||||||||||||||||||||||||||||
| Chronic myelomonocytic leukemia (CMML) | |||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical chronic myeloid leukemia (aCML) | |||||||||||||||||||||||||||||||||||||||||||||||||
| Mixed or unclassified | |||||||||||||||||||||||||||||||||||||||||||||||||
| Juvenile myelomonocytic leukemia (JMML) | |||||||||||||||||||||||||||||||||||||||||||||||||
| Unclassifiable myelodysplastic/myeloproliferative disease | |||||||||||||||||||||||||||||||||||||||||||||||||
Myelosuppressive Disorders
Myelosuppressive disorders are characterized by either pancytopenia or selective lineage deficiency caused by deficient hematopoiesis at the level of the bone marrow. Bone marrow failure may be a result of a congenital disease or an acquired disease.
All Hematopoietic Lineages
- Myelodysplasia (aka Myelodysplastic syndrome): A cause of bone marrow failure characterized by defective stem cells that fail to undergo normal maturation. Bone marrow appears HYPER cellular in myelodysplasia.
- Aplastic anemia (aka Aplastic pancytopenia , bone marrow hypoplasia, hypoplastic bone marrow, bone marrow aplasia, aplastic bone marrow, ehrlich anemia): A cause of bone marrow failure that may be hereditary (Fanconi’s anemia) or acquired (drugs, chemicals, radiation, or viruses). It is a distinct disease characterized by an “empty” bone marrow. Pancytopenia is a manifestation of aplastic anemia. Unlike MDS, the bone marrow appears HYPOcellular in aplastic anemia. Aplastic anemia is not characterized by abnormal mature cells, and the few cells that mature are normal in aplastic anemia. Aplastic anemia is a misnomer since not only RBC (anemia) is affected.
- Paroxysmal nocturnal hemoglobinuria: Bone marrow failure characterized by clonal expansion of a mutated hematopoietic stem cell.
Selective Hematopoietic Lineages
- Pure red cell aplasia (aka erythroblastopenia): There is insufficient production of RBC characterized by absence or deficient erythroblasts in the bone marrow.
- Neutropenia( aka granulocytopenia, granulopenia, agranulocytosis, agranulosis, neutrophilic leukopenia, neutrophilic leukocytopenia, neutrophilic leucopenia, neutrophilic leucocytopenia): Neutropenia is defined absolute neutrophil count < 1.5 x 109/L. Agranulocytosis is defined as severe neutropenia < 0.5 x 109/L. Although agranulocytosis and granulocytopenia should include reduced numbers of all granulocytes (either neutrophils, eosinophils, or basophils), the majority of cases of granulocytopenia are actually neutropenia since neutrophils constitute the majority of leukocytes; the term granulocytopenia almost always refers to deficient neutrophils.
- Amegakaryocytic thrombocytopenia: Thrombocytopenia caused by a reduced number of megakaryocytes in the bone marrow.
Myeloproliferative Disorders
Malignant disease the causes abnormal growth of mature RBC, WBC, and platelets. Unlike myelodysplastic syndromes, myeloproliferative disorders are characterized by the presence of mature cells. Myelofibrosis is the end-stage of all myeloproliferative disorders and is characterized by replacement of bone marrow by fibrosis, which eventually results in a late state of myelosupression (compared with the the early state of myeloproliferation).
- Polycythemia vera (aka polycythemia rubra vera, erythemia, primary polycythemia): Bone marrow disease characterized by proliferation of RBC
- Essential thrombocytosis (aka essential thrombocythemia, primary thrombocythemiais): Bone marrow disease characterized by proliferation of platelets
- Primary myelofibrosis (aka idiopathic myelofibrosis, agnogenic myeloid metaplasia): Idiopathic replacement of bone marrow by fibrosis
- Systemic mastocytosis: Proliferation of mast cells in bone marrow and other organs
- Chronic myelogenous leukemia (CML): Chronic proliferation of myelogenous leukemic blast cells
Mixed or Unclassified Disorders
- Chronic myelomonocytic leukemia (CMML)
- Atypical chronic myeloid leukemia (aCML)
- Juvenile myelomonocytic leukemia (JMML)
- Unclassifiable Myelodysplastic (aka myeloproliferative disease)
Definitions of other Terms
- Pancytopenia: Reduced numbers of all 3 bone marrow cell types: RBCs + WBCs + platelets. It is not a disease, but rather a lab finding that has several causes (e.g. pancytopenia may be due to insufficient production [aplastic anemia], inability of cells or mature [myelodysplasia], or replacement of normal bone marrow with fibrosis [myelofibrosis]).
- Leukopenia: Deficiency of absolute number of leukocytes (generally either lymphocytes or neutrophils). The majority of cases of leukopenia are actually neutropenia since neutrophils constitute the majority of leukocytes.
- Neutrophilic leukopenia / Neutrophilic leukocytopenia / Neutrophilic leucopenia / Neutrophilic leucocytopenia / Neutropenia: Absolute neutrophil count < 1.5 x 109/L
- Eosinophilic leukopenia / Eosinophilic leukocytopenia / Eosinophilic leucopenia / Eosinophilic leucocytopenia / Eosinophilopenia: Reduced absolute number of eosinophils
- Basophilic leukopenia / Basophilic leukocytopenia / Basophilic leucopenia / Basophilic leucocytopenia / Basophilopenia: Reduced absolute number of basophils
- Lymphopenia / Lymphocytopenia: Reduced absolute number of lymphocytes (T-cells or B-cells)
- Myelophthisic Anemia / Myelophthisis: A type of bone marrow failure caused by invasion of abnormal constituents (e.g. fibrosis or tumor).