Treatment Options for Bone Marrow Related Cancers
Acute Myeloid Leukemia (AML)
For patients under 65 years old who are fit for intensive therapy, standard induction chemotherapy consists of an anthracycline (daunorubicin 60-90 mg/m² IV days 1-3 or idarubicin 12 mg/m² IV days 1-3) plus cytarabine 100-200 mg/m² continuous IV infusion days 1-7 (the "7+3" regimen), followed by risk-stratified consolidation therapy. 1, 2
Pre-Treatment Workup and Risk Stratification
- Obtain bone marrow aspirate and biopsy with peripheral blood films for morphology, immunophenotyping, cytogenetics (including FISH), and molecular genetics (PCR for NPM1, FLT3-ITD, CEBPA, IDH, TET2, DNMT3A mutations) 1
- Perform HLA typing of patient and first- and second-degree family members immediately at diagnosis to identify allogeneic stem cell transplant candidates 1, 2
- Assess cardiac function with echocardiography before anthracycline administration, particularly in patients with cardiac risk factors or history of heart disease 1
- Obtain coagulation profile before inserting central venous catheters, especially to detect APL-related coagulopathy 1
- Perform CT chest and abdomen (or chest X-ray and abdominal ultrasound) plus dental survey to identify infectious foci before starting chemotherapy 1
Risk Categories Guide Treatment Decisions
Favorable-risk AML includes: APL with t(15;17), core-binding factor AML with t(8;21) or inv(16), biallelic CEBPA mutation with normal cytogenetics, and normal karyotype with NPM1 mutation without FLT3-ITD 1
Intermediate-risk AML includes: normal cytogenetics without adverse molecular features, and FLT3-ITD with normal karyotype 1
Adverse-risk AML includes: complex karyotype (>3 abnormalities) and monosomal karyotype 1
Induction Chemotherapy
- For patients <65 years: daunorubicin 60-90 mg/m² IV days 1-3 (or idarubicin 12 mg/m² IV days 1-3) plus cytarabine 100-200 mg/m² continuous IV infusion days 1-7 1, 2, 3
- For patients ≥60 years: consider dose reduction to daunorubicin 30 mg/m² IV days 1-2-3 plus cytarabine 100 mg/m² daily for 7 days, though this may not be necessary with optimal supportive care 3
- For FLT3-mutated AML: add midostaurin 50 mg orally twice daily with food on days 8-21 of each induction and consolidation cycle 2, 4
- Patients may require up to three courses of induction therapy to achieve normal-appearing bone marrow 3
- Perform bone marrow aspirate during aplastic phase to monitor blast clearance or persistence 1
Consolidation Therapy Based on Risk
For favorable-risk AML: Administer chemotherapy alone without transplant using high-dose cytarabine 1-3 g/m² every 12 hours on days 1,3,5 for 2-4 cycles 1, 2
For intermediate and high-risk AML: Proceed to allogeneic stem cell transplantation in first complete remission with HLA-identical sibling donor 1, 2
For high-risk patients without sibling donor: Initiate matched unrelated donor search early and consider allogeneic transplantation with unrelated matched donor 1
Acute Promyelocytic Leukemia (APL) - Distinct Treatment
- If APL is suspected, immediately initiate all-trans retinoic acid (ATRA) 25 mg/m² per day before confirmatory molecular results are available 4
- Induction: anthracycline plus ATRA 1
- Consolidation: 1-2 cycles of chemotherapy including ATRA 1
- Maintenance: chemotherapy and ATRA are beneficial in APL 1
- For relapsed APL refractory to ATRA: arsenic trioxide can induce remission 1, 5
Relapsed or Refractory AML
- Patients in second or subsequent remission may qualify for allogeneic transplantation with matched unrelated donor 1
- Carefully selected refractory patients with HLA-matched donor may be offered allogeneic stem cell transplantation, though with limited success and considerable morbidity 1
Response Criteria
Complete remission requires: normal bone marrow cellularity, morphologically normal hematopoiesis, blast levels <5% on bone marrow smears, and peripheral blood count recovery 1, 2
Acute Lymphoblastic Leukemia (ALL)
For adult ALL, induction therapy consists of vincristine, anthracyclines, corticosteroids, with or without L-asparaginase and/or cyclophosphamide, plus CNS prophylaxis with intrathecal chemotherapy, followed by consolidation and maintenance therapy over 2-3 years. 5, 6
Philadelphia Chromosome-Positive (Ph+) B-cell ALL
- Combination of BCR::ABL1 tyrosine kinase inhibitor (TKI) with multiagent chemotherapy or blinatumomab is the mainstay of therapy, resulting in 5-year survival rates exceeding 80% 6
- Achieving complete molecular remission by next generation sequencing may identify patients who can avoid allogeneic stem cell transplantation 6
Philadelphia Chromosome-Negative (Ph-) B-cell ALL
- Chemotherapy backbone (pediatric-inspired or Hyper-CVAD based) combined with novel agents including inotuzumab ozogamicin and blinatumomab 6
- These immunotherapy-chemotherapy regimens achieve 4-year survival rates of 80-85% among patients able to receive treatment 6
- For elderly patients (≥60 years): inotuzumab ozogamicin and blinatumomab in lieu of intensive chemotherapy improves safety and efficacy 6
T-cell ALL
- Combination chemotherapy regimens incorporating pegylated asparaginase and nelarabine are standard 6
- Early T-cell precursor (ETP) ALL is high-risk: consider allogeneic stem cell transplantation 6
- Venetoclax (BCL-2 inhibitor) may be beneficial for ETP-ALL and is under investigation 6
Pediatric ALL Induction Example
- Daunorubicin 25 mg/m² IV on day 1 every week, vincristine 1.5 mg/m² IV on day 1 every week, prednisone 40 mg/m² PO daily 3
- Complete remission typically obtained within four courses; may require up to two additional courses 3
- For children <2 years or <0.5 m² body surface area: calculate daunorubicin dosage based on weight (1 mg/kg) instead of body surface area 3
Adult ALL Induction Example
- Daunorubicin 45 mg/m² IV days 1-2-3, vincristine 2 mg IV days 1,8,15, prednisone 40 mg/m² PO days 1-22 then tapered days 22-29, L-asparaginase 500 IU/kg/day x 10 days IV days 22-32 3
CNS Prophylaxis
- All ALL treatment regimens include CNS prophylaxis and/or treatment 5
- Antimetabolites (methotrexate, cytarabine, mercaptopurine) often included during induction for CNS prophylaxis 5
Relapsed/Refractory ALL
- Best outcomes obtained with combination chemo- and immuno-therapies followed by CAR T-cell consolidation and allogeneic stem cell transplantation 6
Lymphoma
Diffuse Large B-Cell Lymphoma (DLBCL)
For previously untreated DLBCL, administer R-CHOP (rituximab 375 mg/m² plus cyclophosphamide, doxorubicin, vincristine, prednisone) for 6-8 cycles, each cycle lasting 21 days. 7
- Rituximab dosing: 375 mg/m² IV on Days -7 and -3 (prior to Cycle 1) and 48-72 hours prior to Cycles 3 and 5 7
- For patients receiving 8 cycles: also administer rituximab prior to Cycle 7 7
- This regimen demonstrates reduction in risk of progression, relapse, or death compared to chemotherapy alone 7
Pediatric DLBCL/Burkitt Lymphoma/B-cell Acute Leukemia
- For advanced stage (Stage III with elevated LDH or Stage IV): rituximab 375 mg/m² IV administered as six infusions (two doses during each of two induction courses, one during each of two consolidation courses) combined with LMB chemotherapy 7
- LMB chemotherapy includes: corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple drug intrathecal therapy 7
Low-Grade B-cell NHL
- For patients not progressing after 6-8 cycles of CVP chemotherapy: rituximab 375 mg/m² IV once weekly for 4 doses every 6 months for up to 16 doses reduces risk of progression, relapse, or death (hazard ratio 0.36-0.49) 7
Multiple Myeloma
For standard-risk multiple myeloma, treat with lenalidomide plus low-dose dexamethasone (Rd) followed by autologous stem cell transplantation (ASCT); for high-risk patients, use bortezomib-based induction followed by ASCT and bortezomib-based maintenance. 8
Risk Stratification
High-risk features include: 17p deletion, t(4;14), t(14;16), t(14;20), karyotypic deletion 13, or hypodiploidy 8
Standard-risk: all other patients 8
Treatment for Transplant-Eligible Patients
Standard-risk: Lenalidomide plus low-dose dexamethasone (40 mg once weekly) followed by ASCT 8
- Alternative strategy: continue initial therapy after stem-cell collection, reserving ASCT for first relapse if tolerating induction well 8
High-risk: Bortezomib-based induction followed by ASCT, then bortezomib-based maintenance 8
- Use once-weekly bortezomib dosing to reduce toxicity 8
Treatment for Transplant-Ineligible Patients
Relapsed Multiple Myeloma
Indolent relapse: lenalidomide, bortezomib, or alkylators plus low-dose corticosteroids 8
Aggressive relapse: combination of multiple active agents 8
Diagnostic Criteria
Multiple myeloma requires: (1) ≥10% clonal plasma cells on bone marrow examination or biopsy-proven plasmacytoma plus (2) evidence of end-organ damage (CRAB criteria: hypercalcemia, renal insufficiency, anemia, bone lesions) 9
Prognosis
- Median survival for newly diagnosed multiple myeloma: 5-7 years 9
- Multiple myeloma is incurable; management focuses on controlling disease and addressing complications 9
Critical Treatment Setting Requirements
All bone marrow cancer treatment should only be administered in specialized centers with comprehensive hematology/oncology services, bone marrow transplant capabilities, infectious disease expertise, adequate transfusion services, and psycho-oncology support. 1, 2, 4