ACUTE LYMPHOID LEUKEMIAS/LYMPHOMAS
ACUTE LYMPHOBLASTIC LEUKEMIA AND LYMPHOBLASTIC LYMPHOMA
These are more common in children than adults (∼6000 total cases/year). In children, most cases of acute leukemia are of B-cell origin. The majority of cases of acute leukemia in adults and all cases of lymphoblastic lymphoma have tumor cells that appear to be of thymic origin, and pts may have mediastinal masses. Pts usually present with recent onset of signs of marrow failure (pallor, fatigue, bleeding, fever, infection). Hepatosplenomegaly and adenopathy are common. Males may have testicular enlargement reflecting leukemic involvement. Meningeal involvement may be present at diagnosis or develop later. Elevated LDH, hyponatremia, and hypokalemia may be present, in addition to anemia, thrombocytopenia, and high peripheral blood blast counts. The leukemic cells are more often FAB type L2 in adults than in children, where L1 predominates. Leukemia diagnosis requires at least 20% lymphoblasts in the marrow. Prognosis is adversely affected by high presenting white count, age >35 years, and the presence of t(9;22), t(1;19), and t(4;11) translocations. HOX11 expression identifies a more favorable subset of T cell acute lymphoblastic leukemia.
Treatment: Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Successful treatment requires intensive induction phase, CNS prophylaxis, and maintenance chemotherapy that extend for about 2 years. Vincristine, L-asparaginase, cytarabine, daunorubicin, and prednisone are particularly effective agents. Intrathecal or high-dose systemic methotrexate is effective CNS prophylaxis. Long-term survival of 60–65% of pts may be achieved. The role and timing of bone marrow transplantation in primary therapy are debated, but up to 30% of relapsed pts may be cured with salvage transplantation.
This is also more common in children. It is associated with translocations involving the c-myc gene on chromosome 8 rearranging with immunoglobulin heavy or light chain genes. Pts often have disseminated disease with large abdominal masses, hepatomegaly, and adenopathy. If a leukemic picture predominates, it is classified as FAB L3.
Treatment: Burkitt’s Lymphoma/Leukemia
Resection of large abdominal masses improves treatment outcome. Aggressive leukemia regimens that include vincristine, cyclophosphamide, 6-mercaptopurine, doxorubicin, and prednisone are active. CODOX-M and the BFM regimen are the most effective regimens. Cure may be achieved in 50–60%. The need for maintenance therapy is unclear. Prophylaxis against tumor lysis syndrome is important (Chap. 27: Oncologic Emergencies).
ADULT T CELL LEUKEMIA/LYMPHOMA (ATL)
This is very rare; only a small fraction (∼2%) of persons infected with HTLV-I go on to develop the disease. Some HTLV-I-infected pts develop spastic paraplegia from spinal cord involvement without developing cancer. The characteristic clinical syndrome of ATL includes high white count without severe anemia or thrombocytopenia, skin infiltration, hepatomegaly, pulmonary infiltrates, meningeal involvement, and opportunistic infections. The tumor cells are CD4+ T cells with cloven hoof- or flower-shaped nuclei. Hypercalcemia occurs in nearly all pts and is related to cytokines produced by the tumor cells.
Treatment: Adult T Cell Leukemia/Lymphoma
Aggressive therapy is associated with serious toxicity related to the underlying immunodeficiency. Glucocorticoids relieve hypercalcemia. The tumor is responsive to therapy, but responses are generally short lived. Zidovudine and IFN may be palliative in some pts. Lenalidomide and the monoclonal anti-CCR4 receptor antibody, mogamulizumab have antitumor activity.