induction therapy

**General concept:** Induction is the first, high-intensity phase of a multiphase regimen (induction → consolidation/intensification → maintenance). The goal is to rapidly reduce disease burden or immune activity. It is followed by lower-intensity therapy to sustain the response and limit toxicity.

**1. Oncology (hematologic malignancies)** - Goal: complete remission (CR), defined as <5% blasts in marrow with recovery of blood counts. - AML: "7+3" = cytarabine continuous infusion x7 days + an anthracycline (daunorubicin or idarubicin) x3 days. Key toxicities: cytarabine causes cerebellar toxicity and myelosuppression; daunorubicin/doxorubicin cause dilated cardiomyopathy (free radical damage; dexrazoxane is cardioprotective). Acute promyelocytic leukemia (APL, t(15;17), PML-RARA) is treated with ATRA (all-trans retinoic acid) + arsenic trioxide. ATRA causes differentiation syndrome (fever, dyspnea, effusions, weight gain), treated with dexamethasone. APL is associated with DIC. - ALL: multi-agent induction with vincristine, a corticosteroid (prednisone or dexamethasone), and an anthracycline, with or without L-asparaginase. Vincristine causes peripheral neuropathy and SIADH. Asparaginase causes pancreatitis, thrombosis, and hypersensitivity. Ph+ ALL (t(9;22)) adds a TKI. CNS prophylaxis with intrathecal methotrexate is given because the CNS and testes are sanctuary sites. Maintenance uses 6-MP and methotrexate. - Multiple myeloma: induction with a proteasome inhibitor (bortezomib), an immunomodulatory drug (lenalidomide), and dexamethasone, often followed by autologous stem cell transplant. Anti-CD38 antibodies (daratumumab) are frequently added in current practice. - Other: induction chemoimmunotherapy for lymphomas. Neoadjuvant chemotherapy for solid tumors is sometimes also called induction chemotherapy (e.g., head and neck cancer). - Tumor lysis syndrome can occur during induction. It causes hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Prevent it with hydration and allopurinol or rasburicase (rasburicase is contraindicated in G6PD deficiency).

**2. Transplantation** - Induction is intense immunosuppression given perioperatively (at the time of transplant) to reduce acute rejection, especially in high-immunologic-risk recipients. - Agents: - Basiliximab: anti-CD25 (IL-2 receptor α chain) monoclonal antibody that blocks T-cell activation and proliferation. It is generally well tolerated. - Anti-thymocyte globulin (ATG): polyclonal antibody that depletes T cells. Adverse effects include cytokine release syndrome, serum sickness, and leukopenia/thrombocytopenia. - Alemtuzumab: anti-CD52 antibody that causes profound lymphocyte depletion. - High-dose corticosteroids (methylprednisolone) are commonly part of induction. - Maintenance regimen after induction: calcineurin inhibitor (tacrolimus or cyclosporine) + antimetabolite (mycophenolate or azathioprine) ± steroids. Tacrolimus and cyclosporine cause nephrotoxicity. Tacrolimus also causes hyperglycemia and neurotoxicity. Cyclosporine causes gingival hyperplasia and hirsutism. mTOR inhibitors (sirolimus, everolimus) cause hyperlipidemia and impaired wound healing. - Rejection types to know: hyperacute (minutes, preformed antibodies, type II hypersensitivity), acute (weeks to months, T-cell mediated or antibody-mediated), chronic (months to years, with fibrosis, vasculopathy, or bronchiolitis obliterans).

**3. Autoimmune/rheumatologic/renal disease** - Lupus nephritis (class III/IV): induction with high-dose glucocorticoids + mycophenolate or cyclophosphamide, then maintenance with mycophenolate or azathioprine. Belimumab or voclosporin may be added. - ANCA-associated vasculitis (GPA, MPA): induction with glucocorticoids + rituximab or cyclophosphamide, then maintenance with rituximab or azathioprine. - Cyclophosphamide adverse effects: hemorrhagic cystitis (prevent with mesna and hydration), bladder cancer, myelosuppression, and infertility. - Inflammatory bowel disease: induction of remission with steroids or biologics (anti-TNF such as infliximab), followed by maintenance with agents such as azathioprine or biologics. Screen for latent TB before starting anti-TNF therapy.

**4. Other uses of the term** - Induction of anesthesia is a separate meaning: the initial phase of general anesthesia (e.g., propofol, etomidate, ketamine, with a neuromuscular blocker for intubation). - Induction of labor is also separate: oxytocin, prostaglandins (misoprostol, dinoprostone), or cervical ripening. - Antituberculosis therapy has an "intensive phase" (RIPE x2 months) that is conceptually similar. Treatment for H. pylori and for hepatitis C is not called induction.

**High-yield takeaway:** Induction = intensive initial therapy to achieve remission or prevent rejection, and it is distinct from maintenance therapy, which uses lower intensity to sustain the response. Know the drug classes and their signature toxicities for each setting.