What are the indications and considerations for autologous hematopoietic stem cell (AHSC) treatment in adult patients with specific types of cancers, such as multiple myeloma, lymphoma, or leukemia, who have undergone previous treatments like chemotherapy or radiation therapy?

Autologous Hematopoietic Stem Cell Transplantation: Current Indications and Considerations

Primary Indications for Autologous HSCT

Autologous hematopoietic stem cell transplantation (AHSCT) following high-dose chemotherapy is the standard of care for eligible patients with multiple myeloma and relapsed/refractory lymphomas, demonstrating superior response rates and progression-free survival compared to conventional chemotherapy alone. 1

Multiple Myeloma

• All transplant-eligible patients with newly diagnosed multiple myeloma should undergo stem cell harvest after initial induction therapy, collecting sufficient cells for 2 transplants in anticipation of tandem transplantation or salvage therapy. 1
• Autologous HSCT results in higher complete response rates and improved overall survival (54 vs. 42 months) compared to standard therapy, with benefits most pronounced in higher-risk patients. 1
• Young patients with high-risk cytogenetic changes (t(4;14), t(14;16), 17p deletion) should receive autologous HSCT, with allogeneic HSCT reserved as salvage therapy after disease progression post-auto-HSCT. 1
• The median progression-free survival after autologous HSCT in myeloma patients reaches 99.5 months, with overall survival of 157 months. 2

Hodgkin Lymphoma

• Patients with Hodgkin lymphoma who are refractory to initial therapy or relapse after first-line treatment should undergo high-dose chemotherapy followed by autologous HSCT. 1
• Patients relapsing after ≥1 course of autologous HSCT may be considered for allogeneic HSCT as salvage therapy. 1
• Debulking with second-line non-cross-resistant chemotherapy is required before HSCT in chemosensitive patients. 1
• Long-term outcomes show median progression-free survival of 123.8 months and overall survival of 130 months in lymphoma patients undergoing autologous HSCT. 2

Non-Hodgkin Lymphoma

• Autologous HSCT is indicated for patients with aggressive NHL who achieve at least 25% disease reduction after salvage therapy. 3
• The procedure is effective for consolidating response in chemosensitive disease, with cumulative relapse incidence at 5 years of only 19.1%. 2

Acute Lymphoblastic Leukemia

• In Ph-negative high-risk ALL, autologous HSCT does NOT provide significant benefit compared to chemotherapy alone (5-year OS: 32% vs 21%, not statistically significant). 1
• Allogeneic HSCT is superior to autologous HSCT for ALL patients, particularly those with high-risk features. 1

Patient Selection Criteria

Eligibility Requirements

• All candidates must have sufficient liver, renal, pulmonary, and cardiac function to tolerate high-dose chemotherapy. 1
• Age considerations: Most protocols include patients up to 65 years, though outcomes remain favorable in carefully selected older patients. 1
• Disease status: Patients must achieve at least partial response to induction/salvage therapy before proceeding to HSCT. 3

Pre-Transplant Workup

• Complete blood count and comprehensive metabolic panel. 3
• Liver and kidney function assessment. 3
• Pulmonary function tests and cardiac evaluation. 3
• Infectious disease screening (hepatitis B, hepatitis C, HIV). 4
• Chest radiographs and disease-specific imaging (CT/PET). 3
• Dental evaluation to minimize infection risk. 3

Stem Cell Mobilization Strategies

Standard Mobilization Protocol

• Cyclophosphamide followed by granulocyte colony-stimulating factor (G-CSF) 300 µg twice daily is the standard mobilization regimen. 3, 5
• Target CD34+ cell collection: minimum 2 × 10⁶ cells/kg for single transplant, ideally 4-5 × 10⁶ cells/kg to allow for tandem transplant. 5
• Mean infused cell dose: 4.7 × 10⁸ ± 1.7 mononuclear cells per kilogram. 3

Mobilization Failure Predictors

• Prior extensive chemotherapy exposure, particularly alkylating agents. 5
• Advanced age and bone marrow involvement. 5
• Lenalidomide exposure in myeloma patients. 5
• For patients predicted to mobilize poorly, consider upfront plerixafor addition to G-CSF rather than waiting for mobilization failure. 5

Conditioning Regimens

Lymphoma Conditioning

• BEAM (carmustine, etoposide, cytarabine, melphalan) is the standard conditioning regimen for lymphoma patients. 3
• Total body irradiation (TBI) has been abandoned due to equivalent efficacy and less toxicity with chemotherapy-only regimens. 1

Myeloma Conditioning

• High-dose melphalan (typically 200 mg/m²) is the standard conditioning for multiple myeloma. 3
• Dose reduction to 140 mg/m² may be considered in patients >70 years or with renal impairment. 1

Expected Outcomes and Engraftment

Hematopoietic Recovery

• Median time to neutrophil recovery (ANC >500/µL): 9-11 days for myeloma, 11 days for lymphoma. 2
• Median time to platelet recovery (>20,000/µL): 13-14 days for myeloma, 14 days for lymphoma. 2
• Median time to white blood cell recovery: 18.2 ± 5.34 days overall. 3

Long-Term Survival

• Overall survival rate at median follow-up of 104 months: 86% across all autologous HSCT patients. 3
• Transplant-related mortality: approximately 10-15% in contemporary series. 3, 2
• Five-year cumulative mortality incidence: 5.9% in myeloma, 30.9% in lymphoma. 2

Critical Post-Transplant Complications

Acute Complications

• G-CSF prophylaxis should be considered for intensive regimens due to high febrile neutropenia risk. 4
• Anti-infectious prophylaxis and surveillance screening are strongly recommended during active treatment. 4
• Common serious complications occur in approximately 7% of patients (5/69 in recent series). 3

Long-Term Monitoring Requirements

• Complete blood count every 3-4 months during the first two years post-transplant. 4
• Thyroid function testing mandatory for patients receiving neck/mediastinal radiotherapy. 4
• Cardiovascular monitoring should continue long-term for all patients. 4
• Annual breast cancer screening for women >35 years who received chest radiotherapy. 1

Clonal Hematopoiesis Considerations

• Clonal hematopoiesis (CH) is detected in 45% of AML patients, 20% of myeloma patients, and 19% of lymphoma patients undergoing autologous HSCT. 6
• Lymphoma patients with CH-associated mutations have significantly higher relapse rates and reduced progression-free survival (p=0.007). 6
• CH does not significantly impact survival outcomes in AML and myeloma patients undergoing autologous HSCT. 6
• Consider enhanced post-transplant surveillance in lymphoma patients with detected CH mutations. 6

Anemia Management During Treatment

Transfusion Thresholds

• Transfuse red blood cells when hemoglobin falls below 7-8 g/dL or when severe anemia-related symptoms occur at any hemoglobin level. 7
• Target hemoglobin 7-9 g/dL for asymptomatic, hemodynamically stable patients. 7
• Target hemoglobin 8-10 g/dL for symptomatic anemia requiring symptom prevention. 7
• Transfusion rarely indicated when hemoglobin >10 g/dL. 7

ESA Considerations

• ESAs should NOT be used in curative-intent chemotherapy due to increased mortality risk. 8
• For non-Hodgkin lymphoma, CLL, and myeloma patients, observe hematologic response to cancer treatment before considering ESAs. 8
• ESAs increase thromboembolism risk and may increase on-study mortality. 8
• Blood transfusion remains the preferred option in most transplant settings. 7

Common Pitfalls to Avoid

• Do not delay stem cell collection in myeloma patients—harvest should occur after initial induction therapy regardless of transplant timing. 1
• Do not use autologous HSCT for Ph-negative high-risk ALL—allogeneic HSCT is superior. 1
• Do not overlook fertility preservation counseling before treatment initiation for all patients of reproductive age. 4
• Do not use cryopreserved grafts when fresh grafts are feasible—non-cryopreserved HSCT avoids DMSO toxicity and reduces costs while maintaining equivalent outcomes. 2
• Do not collect inadequate CD34+ cells—always target sufficient cells for potential tandem transplant or salvage therapy. 1, 5