Donor Lymphocyte Infusion (DLI)

1. Treatment Overview

The Smart T Web Hospital offers Gujarat's most comprehensive Donor Lymphocyte Infusion (DLI) program, delivering advanced cellular therapy to enhance graft-versus-tumor effects after stem cell transplantation. DLI provides additional immune cells from the original donor to strengthen the therapeutic response while controlling minimal residual disease.

Our program carefully balances effectiveness with safety through precise dosing protocols and comprehensive monitoring. DLI is carefully administered and monitored by our transplant team, with individualized treatment plans based on patient response and clinical parameters.

2. What is Donor Lymphocyte Infusion

2.1 Definition and Concept

Donor Lymphocyte Infusion (DLI) is a cellular therapy that:

• Delivers donor immune cells: T lymphocytes from the original transplant donor
• Enhances graft-versus-tumor effect: Strengthens anti-cancer immune response
• Controls minimal residual disease: Targets remaining cancer cells
• Restores donor chimerism: Ensures complete donor cell engraftment
• Provides cellular immunotherapy: Natural anti-tumor activity

2.2 Historical Development

DLI development milestones:

• 1990s: First clinical applications
• Early success: Chronic myeloid leukemia treatment
• Expanded indications: Multiple hematologic malignancies
• Refined protocols: Dose escalation strategies
• Modern era: Personalized approach

2.3 Scientific Foundation

DLI is based on:

• Graft-versus-leukemia (GVL) effect
• Donor T-cell recognition of tumor antigens
• Immune surveillance mechanisms
• Adoptive cellular immunotherapy principles

3. Mechanism of Action

3.1 Graft-Versus-Tumor Effect

• Donor T-Cell Recognition:
  • Identification of tumor-associated antigens
  • Recognition of minor histocompatibility antigens
  • Activation of cytotoxic T lymphocytes
• Immune Surveillance:
  • Detection of minimal residual disease
  • Elimination of cancer stem cells
  • Prevention of immune escape

3.2 Cellular Mechanisms

• Direct Cytotoxicity:
  • Perforin-granzyme pathway activation
  • Fas-FasL mediated apoptosis
  • TNF-α induced cell death
• Indirect Effects:
  • Cytokine production and signaling
  • Enhancement of antigen presentation
  • Activation of other immune cells

3.3 Chimerism Restoration

• Conversion of mixed to complete chimerism
• Elimination of recipient cells
• Establishment of donor hematopoiesis
• Long-term immune reconstitution

4. Clinical Indications

4.1 Primary Indications

• Disease Relapse:
  • Hematologic relapse post-transplant
  • Molecular relapse detection
  • Progressive disease
• Mixed Chimerism:
  • Declining donor chimerism
  • Graft rejection risk
  • Immune reconstitution failure
• Minimal Residual Disease:
  • Detectable MRD post-transplant
  • Rising MRD levels
  • High-risk disease markers

4.2 Disease-Specific Applications

• Chronic Myeloid Leukemia:
  • BCR-ABL positivity
  • Cytogenetic relapse
  • Molecular relapse
  • Excellent response rates
• Acute Leukemias:
  • Morphologic relapse
  • Molecular persistence
  • Extramedullary disease
  • Variable response rates
• Myelodysplastic Syndrome:
  • Disease progression
  • Cytogenetic abnormalities
  • Transfusion dependence
• Lymphoid Malignancies:
  • Non-Hodgkin lymphoma relapse
  • Multiple myeloma progression
  • Hodgkin lymphoma recurrence

4.3 Prophylactic DLI

• High-risk disease characteristics
• Poor-risk cytogenetics
• History of multiple relapses
• Planned dose reduction

5. Patient Selection Criteria

5.1 Ideal Candidates

• Disease Status:
  • Complete or partial remission
  • Low disease burden
  • Molecular or cytogenetic relapse
  • Mixed chimerism
• Transplant History:
  • Successful engraftment
  • No active GVHD
  • Adequate performance status
  • Stable organ function

5.2 Timing Considerations

• Post-Transplant Timing:
  • Minimum 3 months post-transplant
  • Stable engraftment required
  • Resolution of acute complications
• Disease-Specific Timing:
  • Early molecular relapse: immediate
  • Mixed chimerism: 6-12 months
  • Prophylactic: 3-6 months

5.3 Exclusion Criteria

• Active acute GVHD (grade ≥2)
• Extensive chronic GVHD
• Severe organ dysfunction
• Active uncontrolled infection
• High disease burden
• Poor performance status

6. Pre-Treatment Preparation

6.1 Patient Assessment

• Disease Evaluation:
  • Bone marrow assessment
  • Imaging studies
  • Molecular monitoring
  • Chimerism analysis
• Clinical Evaluation:
  • Performance status assessment
  • Organ function testing
  • GVHD evaluation
  • Infection screening

6.2 Donor Evaluation

• Donor Availability:
  • Original donor contact
  • Consent for additional donation
  • Health status assessment
• Donor Screening:
  • Medical history update
  • Physical examination
  • Laboratory testing
  • Infectious disease screening

6.3 Treatment Planning

• Dose selection strategy
• Escalation schedule
• Monitoring plan
• GVHD prophylaxis consideration

7. Lymphocyte Collection Process

7.1 Collection Methods

• Apheresis Collection:
  • Standard lymphocyte apheresis
  • 4-6 hour procedure
  • Outpatient setting
  • Multiple collections possible
• Whole Blood Collection:
  • Standard blood donation
  • Laboratory lymphocyte isolation
  • Lower cell yields
  • Simple procedure

7.2 Target Cell Doses

• Initial Dose Levels:
  • 1 × 10⁷ CD3⁺ cells/kg (low dose)
  • 1 × 10⁸ CD3⁺ cells/kg (intermediate)
  • 5 × 10⁸ CD3⁺ cells/kg (high dose)
• Disease-Specific Dosing:
  • CML: Lower doses effective
  • Acute leukemia: Higher doses needed
  • Lymphoma: Variable dosing

7.3 Collection Quality Control

• Total nucleated cell count
• Lymphocyte subset analysis
• Viability assessment
• Sterility testing
• Endotoxin screening

8. Cell Processing & Quality Control

8.1 Cell Processing Steps

• Initial Processing:
  • Volume reduction if needed
  • Red blood cell removal
  • Platelet depletion
  • Final volume adjustment
• Cell Washing:
  • Removal of plasma proteins
  • ABO incompatibility management
  • Final buffer preparation

8.2 Quality Control Testing

• Cell Count Analysis:
  • Total nucleated cell count
  • Lymphocyte percentage
  • CD3⁺, CD4⁺, CD8⁺ enumeration
  • Viability assessment
• Safety Testing:
  • Sterility cultures
  • Endotoxin testing
  • Mycoplasma screening
  • Gram staining

8.3 Product Release Criteria

• Target cell dose achieved
• Viability >70%
• Sterility test negative
• Endotoxin <5 EU/kg
• Documentation complete

9. Administration Protocol

9.1 Pre-Administration

• Patient Preparation:
  • Baseline vital signs
  • Pre-medication if indicated
  • IV access confirmation
  • Emergency equipment ready
• Product Preparation:
  • Final quality review
  • Volume and concentration check
  • Administration rate calculation

9.2 Infusion Process

• Administration Method:
  • Central venous access preferred
  • Gravity infusion or pump
  • Standard blood filter use
  • Infusion rate: 2-5 ml/minute
• Monitoring During Infusion:
  • Vital signs every 15 minutes
  • Clinical assessment
  • Adverse reaction monitoring
  • Documentation requirements

9.3 Post-Administration

• Observation period (2-4 hours)
• Vital sign monitoring
• Symptom assessment
• Documentation completion

10. Dosing Strategies

10.1 Dose Escalation Protocol

• Starting Doses:
  • CML: 1 × 10⁷ CD3⁺ cells/kg
  • Acute leukemia: 1 × 10⁸ CD3⁺ cells/kg
  • Lymphoma: 5 × 10⁷ CD3⁺ cells/kg
• Escalation Schedule:
  • 8-12 week intervals
  • 10-fold dose increases
  • Maximum: 1 × 10⁹ CD3⁺ cells/kg
  • Response-based modification

10.2 Modified Approaches

• CD8⁺ Depletion:
  • Reduced GVHD risk
  • Preserved GVL effect
  • Higher starting doses
• Suicide Gene Approach:
  • Genetically modified lymphocytes
  • GVHD safety mechanism
  • Investigational protocols

10.3 Individualized Dosing

• Patient risk factors
• Disease characteristics
• Prior GVHD history
• HLA matching status

11. Post-Infusion Monitoring

11.1 Early Monitoring (Days 1-30)

• Clinical Assessment:
  • Daily evaluation first week
  • GVHD symptom screening
  • Infection surveillance
  • Performance status
• Laboratory Monitoring:
  • Complete blood count
  • Comprehensive metabolic panel
  • Liver function tests
  • Inflammatory markers

11.2 Response Assessment

• Disease Response:
  • Molecular monitoring
  • Cytogenetic analysis
  • Flow cytometry
  • Imaging studies
• Chimerism Analysis:
  • Serial chimerism studies
  • T-cell subset chimerism
  • Conversion to full donor

11.3 Long-term Follow-up

• Monthly clinical assessments
• Quarterly disease evaluations
• Annual survivorship planning
• Late effects screening

12. Treatment Outcomes

12.1 Disease-Specific Responses

• Chronic Myeloid Leukemia:
  • Complete remission: 70-90%
  • Molecular remission: 60-80%
  • Durable responses common
  • Low GVHD rates
• Acute Leukemias:
  • Overall response: 30-50%
  • Complete remission: 20-40%
  • Variable durability
  • Higher GVHD risk
• Multiple Myeloma:
  • Response rates: 40-60%
  • Disease stabilization
  • Quality of life improvement

12.2 Survival Outcomes

• Overall Survival:
  • CML: 80-90% at 5 years
  • Acute leukemia: 40-60%
  • Disease-dependent variation
• Progression-Free Survival:
  • Improved disease control
  • Reduced relapse rates
  • Extended remission duration

12.3 Quality of Life

• Reduced transfusion dependence
• Improved functional status
• Enhanced immune reconstitution
• Better long-term outcomes

13. Side Effects & Risks

13.1 Acute Side Effects

• Infusion-Related Reactions:
  • Fever and chills (10-20%)
  • Nausea and vomiting
  • Headache
  • Hypotension (rare)
• Early Complications:
  • Cytopenias
  • Fatigue
  • Infection risk

13.2 Graft-Versus-Host Disease

• Acute GVHD:
  • Incidence: 40-70%
  • Skin, liver, GI involvement
  • Dose-dependent risk
  • Treatable with immunosuppression
• Chronic GVHD:
  • Incidence: 30-50%
  • Multi-organ involvement
  • Quality of life impact
  • Long-term management needed

13.3 Risk Mitigation

• Careful dose selection
• Patient risk assessment
• Early GVHD detection
• Prompt treatment initiation
• Experienced team management

14. GVHD Prevention & Management

14.1 Prevention Strategies

• Dose Escalation:
  • Start with lowest effective dose
  • Gradual dose increases
  • Response monitoring
• CD8⁺ Depletion:
  • Selective T-cell depletion
  • Preserved GVL effect
  • Reduced GVHD risk

14.2 Early Detection

• Clinical Monitoring:
  • Skin examination
  • GI symptom assessment
  • Liver function monitoring
• Biomarker Testing:
  • GVHD biomarkers
  • Inflammatory markers
  • Tissue biopsy when indicated

14.3 Treatment Protocols

• First-line: Corticosteroids
• Second-line: Calcineurin inhibitors
• Refractory: Novel agents
• Supportive care measures

15. Treatment Cost

15.1 Cost Components

• Collection and Processing:
  • Donor lymphocyte collection: ₹75,000 - ₹1,25,000
  • Cell processing: ₹25,000 - ₹50,000
  • Quality control testing: ₹15,000 - ₹25,000
• Administration:
  • Day care admission: ₹10,000 - ₹15,000
  • Monitoring and support: ₹5,000 - ₹10,000

15.2 Follow-up Costs

• Monthly monitoring: ₹15,000 - ₹25,000
• Response assessment: ₹20,000 - ₹30,000
• GVHD management: Variable

15.3 Insurance and Support

• Insurance coverage available
• Government scheme eligibility
• Hospital financial assistance
• Payment plan options

16. Our Expert Team

16.1 Medical Leadership

• Dr. Rajesh Patel - Transplant Director
  • DM Hematology, 25+ years experience
  • 200+ DLI procedures performed
  • International training in cellular therapy
• Dr. Priya Sharma - Cellular Therapy Director
  • PhD Immunology
  • DLI protocol development expert
  • Research in adoptive immunotherapy

16.2 Multidisciplinary Team

• Transplant physicians
• Apheresis specialists
• Cellular therapy nurses
• Laboratory technologists
• Patient coordinators

17. Advanced Technology

17.1 Collection Technology

• State-of-the-art apheresis systems
• Automated cell processing
• Real-time monitoring
• Quality assurance protocols

17.2 Laboratory Capabilities

• Flow cytometry analysis
• Cell counting and viability
• Sterility testing
• Molecular monitoring

17.3 Monitoring Systems

• Chimerism analysis
• MRD detection
• GVHD biomarkers
• Response assessment

18. Research & Clinical Trials

18.1 Current Studies

• Optimal dosing strategies
• GVHD prevention methods
• Response biomarkers
• Quality of life outcomes

18.2 Novel Approaches

• Genetically modified lymphocytes
• Targeted cell subsets
• Combination therapies
• Prophylactic applications

18.3 Collaborative Research

• Multi-center trials
• International partnerships
• Academic collaborations
• Industry partnerships

19. Patient Support Services

19.1 Pre-Treatment Support

• Education and counseling
• Donor coordination
• Insurance authorization
• Financial counseling

19.2 During Treatment

• Dedicated nursing care
• Patient advocacy
• Family support
• Social services

19.3 Long-term Care

• Follow-up coordination
• Survivorship programs
• Support groups
• Quality of life programs

20. Frequently Asked Questions