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Blood cancer

Blood cancer is a term that refers to cancers that affect our blood-forming organ, or bone marrow. Blood cancers include leukemia, myeloid neoplasms, and plasma cell malignancies.

The term leukemia describes a number of cancers of the bone marrow characterized by increased growth and/or impaired maturation. The four major types of leukemia are acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). More than 50,000 new cases of leukemia will be diagnosed in the United States this year.

Diagnosis & treatment

AML is highly heterogeneous and responses to AML therapy vary between individual patients. Based on cytogenetic and molecular markers, AML can be divided into several categories with distinct disease risk. Genomic-wide sequencing has identified over 20 mutations recurrently seen in AML. Of these, testing for mutations in FLT3, NPM1, and CEBPA is critical in determining how patients who enter first remission should be treated. Optimal induction therapy in AML involves the use of an anthracycline and cytarabine. Patients up to age 60 who achieve a complete response, except those with favorable cytogenetic/molecular risk profile who achieve an early first complete response and have no evidence of minimal residual disease after induction, should be considered for allogeneic hematopoietic stem cell transplantation, especially if comorbidity scores are low and an HLA-matched donor is available. Patients with acute promyelocytic leukemia should receive all-trans retinoic acid and arsenic trioxide as part of induction and/or consolidation therapy.

ALL occurs both in children and adults. ALL can be categorized according to morphology, histochemistry, cell surface markers, cytogenetics, and molecular biology. Induction therapy in adult ALL should include vincristine, prednisone, an anthracycline, and asparaginase. With such regimens, complete remissions can be achieved in more than 80% of patients. Patients with Philadelphia chromosome-positive ALL should receive a tyrosine kinase inhibitor in combination with chemotherapy. Allogeneic transplantation is an important post-remission treatment modality except in some patients who have highly chemosensitive disease.

CML was the first malignant disease found to be consistently associated with a specific cytogenetic abnormality, the Philadelphia chromosome, a translocation between chromosomes 9 and 22. Tyrosine kinase inhibitors such as imatinib, nilotinib, and dasatinib are spectacularly effective in patients with newly diagnosed chronic phase CML, leading to complete hematologic and cytogenetic remissions for the majority of patients.

CLL is the most prevalent adult leukemia in Western countries. There are no known risk factors for CLL. Distinguishing CLL from other diseases such as hairy cell leukemia, marginal zone lymphoma, and mantle cell lymphoma is based on the morphologic appearance of the cells and the distinct immunophenotype of the malignant cells. First line chemoimmunotherapy offers prolonged survival in patients with CLL. The treatment protocol chosen is based on the medical fitness of the patient and the presence or absence of del(11q) or del(17p). Recently, the oral Bruton tyrosine kinase inhibitor ibrutinib was approved for first-line therapy of CLL with del(17p).

The term myeloid neoplasm encompasses several disorders including AML, myelodysplastic syndrome, (MDS), and myeloproliferative neoplasms (MPNs). MDS is the most common class of acquired bone marrow failure syndrome in adults. More than 30,000 new cases of MDS will be diagnosed in the United States this year.

MDS generally affects older individuals, with a median age of 65 at diagnosis. Only 10% of patients are younger than 50 years at diagnosis. The three most important factors that predict outcome for patients with MDS are percentage of marrow blasts, karyotype, and number of peripheral cytopenias. The treatment strategy is based on the disease risk. The goals of therapy include reducing consequences related to cytopenias, improving quality of life in patients with low risk disease, and improving survival for patients with higher risk disease.

MPNs are a heterogeneous group of hematologic disorders that include CML, polycythemia vera (PV), primary myelofibrosis (MF), essential thrombocythemia (ET), and myeloproferative neoplasms otherwise unclassified. The median life expectancy varies considerably between the various disorders because of varying risks for thrombosis, bleeding, and clonal evolution. The goals of therapy for myeloproferative neoplasms include alleviation of symptoms, prevention of thrombosis, minimizing risk of progression to MF (for patients with PV or ET), reducing risk of leukemia transformation (for patients with MF), and improvement in survival.

Multiple myeloma is a plasma cell neoplasm characterized by osteolytic bone lesions, anemia, hypercalcemia, and renal failure. Multiple myeloma accounts for 1% of all cancers and about 10% of all hematologic cancers. Myeloma is twice as common in the African American population compared with the white population. Benign monoclonal gammopathy (BMG) and smoldering multiple myeloma are asymptomatic plasma cell disorders that need to be distinguished from multiple myeloma. Early intervention with lenalidomide has shown promise in the treatment of smoldering multiple myeloma, but the standard of care remains observation in this patient population. The most common presenting symptoms of multiple myeloma are fatigue and bone pain. Patients who are considered potential candidates for autologous stem cell transplantation (ASCT) are first treated with bortezomib, lenalidomide, and dexamethasone, followed by stem cell harvest, followed by either early ASCT or continuation of initial treatment regimen with delay of ASCT until relapse.