Leukemia Treatment and Multisystem Effects

Leukemia Treatment

• Treatment focuses on symptom relief and achieving remission or cure.
• Common treatment methods include chemotherapy, targeted therapy, radiation therapy, and bone marrow/stem cell transplantation.
• Induction chemotherapy aims to induce remission, while consolidation chemotherapy sustains it
• Children with acute leukemia have a higher cure rate compared to adults, though long-term remission is achievable for both.

Multisystem Effects

• Neurologic
  • Headache, altered level of consciousness (LOC), cranial nerve impairment, potential complications: subarachnoid and retinal hemorrhages, seizures, coma
• Respiratory
  • Dyspnea on exertion, pharyngitis, sore throat, frequent respiratory infections, potential complication: pulmonary bleeding
• Gastrointestinal
  • Anorexia, nausea, oral ulcerations/infections, bleeding gums, gingival hyperplasia, abdominal pain, hepatomegaly, occult GI bleeding
• Urinary
  • Urinary tract infection, hematuria, potential complication: renal insufficiency or failure
• Musculoskeletal
  • Weakness, bone tenderness/pain, joint pain
• Metabolic Processes
  • Malaise, lethargy, heat intolerance, diaphoresis, chills, fever, night sweats, weight loss
• Cardiovascular
  • Tachycardia, palpitations, orthostatic hypotension, heart murmurs, hematomas, edema, potential complications: hemorrhage, thrombophlebitis
• Hematologic
  • Anemia, thrombocytopenia, leukopenia, bleeding (epistaxis), splenomegaly, potential complication: disseminated intravascular coagulation (DIC)
• Immunologic
  • Frequent or recurrent infections, lymphadenopathy, potential complications: abscesses, septicemia
• Integumentary
  • Skin and mucous membrane pallor, petechiae, bruising/purpura, ulcerations, chloromas (skin infiltrations near bony prominences)

Diagnostic Tests

• Complete blood count with differential (CBC with diff): evaluates cell counts (RBCs, WBCs, platelets), hemoglobin and hematocrit levels, and morphology of WBCs.
• Platelet count: identifies possible thrombocytopenia and bleeding risk.
• Bone marrow examination: provides information about marrow cells, erythropoiesis, and maturity of erythro- and leukopoietic cells.

Surgical Procedures

• Bone marrow transplant (BMT)
  • Treatment of choice for certain leukemia types.
  • Often used with or after chemotherapy or radiation.
  • Allogeneic BMT uses donor bone marrow, ideally from a sibling with closely matched tissue antigens or an unrelated donor.
  • Requires high-dose chemotherapy and potentially total body irradiation to destroy leukemic cells.
  • Donor bone marrow is aspirated and infused through a central venous line.
  • Post BMT, the patient is critically ill and at high risk for infections and bleeding due to WBC and platelet depletion.
  • Autologous BMT utilizes the patient's own bone marrow, often stored during remission, to restore bone marrow function after treatment.
  • Involves aspirating and freezing bone marrow, then thawing it and infusing it intravenously with antibiotics and steroids after high-dose chemotherapy or radiation.
• Stem Cell Transplant (SCT)
  • Alternative to BMT, resulting in complete replacement of the recipient's blood cell lines with donor stem cell-derived cells.
  • Similar treatment as BMT beforehand.
  • Donors must have closely matched tissue antigens.
  • Hematopoietic growth factors (GM-CSF, G-CSF) are administered to the donor to increase stem cell concentration in their peripheral blood, allowing for stem cell harvesting and transplantation.
  • Peripheral blood is collected, WBCs are separated, and infused via a central venous catheter.
  • Umbilical cord blood can also be used as a source of stem cells.

Graft-Versus-Host Disease (GVHD)

• A potential complication of allogeneic BMT or SCT, occurs when donor T lymphocytes attack the recipient's liver, skin, and GI tract.
• Acute GVHD: develops within days to 6 months after transplant, characterized by a pruritic maculopapular rash and other symptoms like jaundice, nausea, vomiting, diarrhea, and dry eyes.
• Chronic GVHD: develops over 3 months after transplant and can persist for life, accompanied by chronic pain, fatigue, weakness, and shortness of breath.
• Treated with antibiotics and corticosteroids.

Pharmacologic Therapy

• Two main approaches: killing cancerous cells and altering the body's response to cancer cells.
• Chemotherapy: cytotoxic medications given in induction and postremission phases.
• Induction chemotherapy: high doses to eradicate leukemic cells, but can also harm stem cells and affect normal blood cell production.
• Postremission chemotherapy: lower doses, aimed at eradicating remaining leukemic cells, preventing relapse, and prolonging survival.
• Biological therapy: uses cytokines like interferons and interleukins, modifying the body's response to cancer cells and potentially having cytotoxic effects.
• Interferons: proteins normally produced in response to antigens, modulating immune function and inhibiting abnormal cell proliferation.
• Interferon alfa: used for certain leukemias, particularly chronic myeloid leukemia (CML), with common side effects like flu-like symptoms, fatigue, weight loss, muscle and joint pain.

Medications

• Colony-Stimulating Factors: stimulate the production and differentiation of neutrophils, aiding in recovery after chemotherapy.
• Cytokines: modify the body's response to cancer cells, potentially causing cell lysis.
• Drug Antibody Conjugates: target specific antigens on tumor cells, delivering cytotoxic agents to cause cell death.
• FLT3 Inhibitors: target the FLT3 protein involved in cell proliferation, inhibiting signaling and inducing cell death in leukemic cells.

Monoclonal Antibodies

• Alemtuzumab: Targets CD52 antigen on B and T cells, leading to cell death in chronic lymphocytic leukemia (CLL).
• Obinutuzumab: Targets CD20 antigen on premature and mature B cells, resulting in cell death and depletion in CLL.
• Ofatumumab: Binds to CD20 to cause cell death in CLL.
• Rituximab: Binds to CD20 antigen on lymphoma cells, preventing cell cycle activation and resulting in cell death in CLL.

Monitoring

• General: CBC, liver and renal function tests, infusion reactions, cardiovascular status
• Alemtuzumab: Stroke symptoms (neck pain, weakness, facial droop), infection, immune thrombocytopenia, progressive multifocal leukoencephalopathy (PML), depression, suicide ideation
• Obinutuzumab: Tumor lysis syndrome, infection, hepatitis, new neurologic symptoms
• Rituximab: Stroke symptoms, infection, neutropenia, tumor lysis syndrome, PML, hypersensitivity reactions

Patient Advice

• Alemtuzumab: Report neutropenia (bleeding, easy bruising), infusion reactions, infection, thyroid disorder, stroke, PML, depression, suicide ideation
• Obinutuzumab: Report infusion reaction, tumor lysis syndrome, infection, hepatitis, new neurologic symptoms
• Rituximab: Report infection, neutropenia, tumor lysis syndrome, PML, hypersensitivity reactions

Biological Response Modifiers (Colony-Stimulating Factors)

• Stimulate bone marrow recovery following chemotherapy
• Examples: granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF)
• Side effects: bone pain, fever, chills, anorexia, muscle aches, lethargy

Radiation Therapy

• Uses high doses of x-rays or other energy to damage cellular DNA, preventing cell division and multiplication.
• Targets rapidly dividing cells (e.g., bone marrow, cancer cells).
• Normal cells recover better from radiation damage than cancer cells.

This quiz covers the treatment strategies for leukemia including chemotherapy, targeted therapy, and stem cell transplantation. It also explores the multisystem effects of leukemia on neurologic, respiratory, gastrointestinal, and urinary functions. Test your knowledge on symptom management and the complexities of leukemia treatments.