This 30 year old man has presented with a worrisome complex of symptoms: 4 months of dull pain in the right hip joint, in association with an intermittent, low-grade fever. The differential diagnoses for this presentation are broad, and include a variety of infectious, inflammatory, and neoplastic conditions. However, his full blood count reveals an even more worrisome finding: anemia and thrombocytopenia, in association with a leukocytosis - but absolute neutropenia; a follow up peripheral blood smear reveals 15% blast cells. These features are generally seen in infiltrative disorders of the bone marrow, such as leukemia, myelofibrosis and metastatic neoplasms; thus, a neoplastic etiology seems to be the most likely cause of his presentation. Note also that the hip joint is clinically normal (as is the knee joint, excluding referred pain); this too is more suggestive of a neoplastic etiology, as opposed to an infectious or inflammatory pathology. The x-ray appearance of reduced density of the right iliac bone, acetabular bone and marrow spaces lends further credence towards the possibility of marrow infiltration. Aspiration and biopsy of the bone marrow is an essential next step; this reveals the presence of fibrotic marrow with areas of hyperplasia while aspiration and special staining techniques demonstrate 36% blast cells which are of myeloid lineage. Note that according to the world health organization (WHO) classification, the presence of more than 20% blasts in the bone marrow is diagnostic of acute leukemia; thus, this appears to be acute myeloid leukemia (AML). Flow cytometric immunophenotyping is important to confirm the lineage of blast cells and further classify the subtype of AML; this confirms the myeloid phenotype. Prior to initiation of therapy, cytogenetic analysis should be carried out in order to identify the specific genetic defect involved; this is because certain genetic changes in AML are associated with favorable outcomes and the therapeutic process can be altered to facilitate this in some instances. Chemotherapy is currently the mainstay of treatment; daunorubicin and cytarabine are the most commonly used chemotherapeutic agents for induction of remission. Blood transfusion is only required if the Hb count is less than 7 g/dL, and thus is not indicated in this patient. Radiotherapy is indicated in patients in whom there is spread to the spinal cord or brain; or prior to stem cell transplantation. Stem cell transplantation is not indicated right now, but may be considered if this patient goes into remission following the initial course of chemotherapy.
Acute myeloid leukemia (AML) is a hematological malignancy where there is overproliferation and lack of differentiation of stem cells, resulting in the accumulation of myeloblasts in the bone marrow and blood. The disease is the most common hematological malignancy among adults, with the median age of presentation in the United States being 68 years; in this age group, the incidence is 17.6 per 100,000 persons. The clinical features of AML are due to progressive marrow infiltration; the resultant pancytopenia gives rise to the characteristic clinical findings. Leukemic infiltration of the organs can also give rise to a variety of symptoms and signs; these include hepatomegaly, splenomegaly, lymphadenopathy and bone pain. Collections of leukemic cells are well known to occur in the skin (leukemia cutis), gingiva and central nervous system. Some patients may present as an emergency, if the rapidly proliferating myeloblasts occlude the blood supply to areas of the central nervous system or lungs. Basic investigations in a patient suspected of AML include a complete blood count and blood smear; the white cell count will generally be elevated, whereas the neutrophil count will be low. Red cells and platelets may be reduced in varying degrees. A blood smear is important in demonstrating the morphological type of the circulating blasts; these are distinguished by the large nuclei, prominent nucleoli and scanty cytoplasm. Note that azurophilic granules and Auer bodies are findings characteristic of myeloid cells. Bone marrow aspiration and biopsy is the lynchpin diagnostic test; according to the world health organization (WHO) classification, the presence of myeloblasts amounting to more than 20% of nucleated cells in the marrow is diagnostic of AML. Note that cytochemical staining of marrow specimens with myeloperoxidase is confirmatory of a myeloid lineage; this aids in distinguishing AML from lymphoblastic leukemias. Once the diagnosis of AML has been established, the next step is to determine the subtype, as this often correlates with the prognostic outcome; immunophenotypic flow cytometry is a valuable test in this regard. The morphological subtypes of AML have been classified by the French-American-British (FAB) group into 9 categories; however, the latest classification by the WHO contains only 4. These classifications are aimed at identifying subtypes with similar biological properties and prognoses. The determination of specific chromosomal aberrations of myeloblasts by means of cytogenetic analysis aids in categorizing the subtypes even further. It has been demonstrated that certain subtypes thus identified have distinct outcomes. Renal and liver function tests, clotting profiles and cerebrospinal fluid (CSF) analysis may be required in order to identify complications of the disease, such as renal and hepatic failure, disseminated intravascular coagulation (DIC) and leukemic spread to the central nervous system (CNS); note that the last is quite rare in AML. The treatment of AML is aimed at induction of remissio, and prevention of relapse. Treatment recommendations vary according to the age of the patient, health status, and subtype of AML. Commonly used induction agents include cytarabine and daunorubicin; drugs such as idarubicin or mitoxantrone may also be used. Remission is said to be achieved when the bone marrow myeloblast count is less than 5%, along with the normalization of peripheral blood count. Post induction or consolidation therapy involves high dose chemotherapy, or autologous or allogeneic stem cell transplantation; the choice mainly depends on the risk as determined by cytogenetics. Stem cell transplantation should be particularly considered in patients younger than 60 years and in those who have HLA-matched siblings or a donor. Supportive therapy involves blood transfusion if the count is less than 7 g/dL, and platelet transfusion if the count is reduced beyond 20,000/µL without signs of blood loss. In case of bleeding, the transfusion threshold may be lowered. Prophylactic antibiotics, antivirals and antifungals are recommended by certain authorities in patients undergoing extensive chemotherapy. Hyperuricemia is frequently identified in patients during chemotherapy; allopurinol should generally be prescribed until the resolution of hyperuricemia. The prognosis of AML depends heavily upon the age of the patient, previous hematological disorders, overall health of the individual, and most importantly the cytogenetics; individuals with favourable cytogenetics such as the t(15;17), t(8;21), or inv(16) mutations, have a significantly better survival rate. Note that the survival of patients with AML has progressively improved over the past few years, due to advancements in treatment. Individuals younger than 60 years show rates of response approximating 70% to 80%. However, overall survival remains close to 30%.