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Radiotherapeutic palliation of bone marrow diseases—leukemia and multiple myeloma
Introduction
Hematologic malignancies arising from bone marrow cell populations classically include leukemias, either of lymphocytic or myelogenous origin, and multiple myeloma (MM), of plasma cell origin. The mainstay of definitive therapy for these malignancies is high-dose chemotherapy with local therapy, such as radiation therapy (RT) typically reserved for palliation. However, in the modern era of improved systemic agents and prolonged patient survival, the management of the many permutations of relapsed disease has become increasingly common, which in turn often complicates the delivery of palliative RT for local symptoms. There are many exciting, targeted agents being developed for both leukemia and myeloma, including receptor tyrosine kinase inhibitors, immunotherapies, and cellular therapies (i.e., chimeric antigen receptor [CAR] T-cell therapies). In addition, we are witnessing an evolution of relapsed disease presentation with more extra-medullary disease as patients traverse through multiple lines of therapy. As more lines of marrow-toxic and lymphocyte-reliant therapies become available, preservation of these compartments should be kept in mind as palliative RT regimens are considered. Palliation of bone marrow malignancies requires careful planning and knowledge of the various techniques possible in the treatment of the diverse local manifestations of what are otherwise considered systemic diseases. We provide an outline of these in this section.
Palliative radiation therapy for leukemia
Modern systemic therapy for leukemia can achieve control of disease in the blood and bone marrow. Nevertheless, symptomatic relapse outside the blood and bone marrow remains a matter of quality of life (QoL) and at times may warrant emergent local therapy. Such relapses can be divided anatomically into either central nervous system (CNS) or other extramedullary sites. Scenarios with unique clinical considerations include splenomegaly, testicular relapse, and parenchymal lung disease. The high radiosensitivity of leukemic cells renders RT an effective palliative strategy; in select cases, it may be used to achieve durable control of disease as part of an intensive regimen with systemic therapy. The approach of palliative RT in these settings, including dose, technique, and unique clinical considerations of palliative RT are outlined in the following sections.
Extramedullary leukemia
Extramedullary leukemia includes the entities of chloroma , which is any extramedullary collection of immature myeloid cells, and leukemia cutis , which strictly refers to skin involvement. These are most common in patients with acute myeloid leukemia (AML). RT dose and technique depends on the prognosis, plan for systemic therapy, as well as the presence of emergent symptoms resulting from the mass effect on vital organs.
Chloroma most commonly involves the lymph nodes, soft tissue, testes, bone, peritoneum, and gastrointestinal tract. These range from asymptomatic to emergent mass-effect symptoms, such as airway or neurologic compromise. They usually present in the context of disease relapse. Imaging characteristics vary with anatomic site.
The dose depends on the clinical scenario and ranges from a total of 6 to 24 Gy in ∼2 Gy fractions; lower doses are typically used in scenarios of poor prognosis for purely symptomatic relief, while higher total doses are used in the context of a prognosis where durable control would provide benefit. Simulation techniques and image guidance likewise vary with anatomic sites. Local control rates are excellent, with rates of symptomatic relief up to 95%. The exquisite radiosensitivity of leukemic cells often results in quick response and may be observed as early as the day after the first treatment.
Leukemia cutis represents a minority of hematologic-associated skin lesions and is associated with a poor prognosis. It more commonly presents synchronously or following a systemic leukemia diagnosis, not before. The most common sites are legs, followed by arms, back, chest, scalp, and face. RT assumes a palliative role, except in the rare context of bone marrow remission. Palliative RT is limited to symptomatic lesions and rarely requires total skin electron beam therapy (TSEBT) unless a large surface area of the skin is symptomatic.
As in chloroma, the dose ranges from a total of 6 to 24 Gy in ∼2 Gy fractions. , The typical technique entails a clinical set up with electrons and bolus directed at the symptomatic lesions. Lower electron energies of 6 to 9 MeV with bolus as needed are appropriate. Responses are achieved in up to 90% of patients, with many achieving a complete response (CR). However, long-term local control even at one year is poor, with skin and marrow relapse most often being concomitant.
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