Post Transplant Donor Lymphocyte Infusions (DLI)
Definition of Disease Progression
Disease
|
Progression
|
Multiple Myeloma
|
- Increasing bone pain or an increase in serum or urine monoclonal protein by 25% and/or serum free light chains.
|
CLL, NHL, & Hodgkin Lymphoma
|
- New sites of lymphadenopathy, or increase of 25% in lymph node size (as assessed by CT scans), or
- Blood or bone marrow involvement with clonal B cells (lymphoma), or
- Increase of 25% bone marrow involvement (CLL), or
- Increase of 25% blood involvement (if lymphocyte count less than 50 x 109/L) with clonal B cells (CLL).
|
AML/ALL
|
- Any evidence of relapse (>5% blasts) by morphologic evaluation of the bone marrow aspirate, or other evidence of relapse.
|
CML
|
- Inability to control granulocyte or platelet counts, or
- Increase in baseline number of metaphases that demonstrate the Ph+ chromosome by >25%, or rise in BCR/ABL, or
- Any other new clonal abnormality by cytogenetic evaluation, or
- Evidence of transformation to accelerated phase or blast crisis.
|
MDS
|
- Any evidence by morphologic evaluation of the bone marrow aspirate of new blasts (>5%), or other evidence of relapse, or
- Worsening cytopenia attributable to underlying disease.
|
|
|
Guidelines for post-transplant management of patients in the absence of GvHD
(PD: progressive disease, CR: complete remission)
DLI Decision-making Guidelines for High Risk Patients without GvHD and off all Immunosuppression
This is based on chimerism status and disease status on day +56. Management decisions must be taken by day +65.
Chimerism
|
Disease Status
|
Action
|
Full Donor Chimerism
>95% T-cells of donor origin at any time
|
CR
|
NONE
|
Continuing response
|
Continue to monitor for response and chimerism at monthly intervals
|
Stable or increasing tumour markers
|
DLI
|
Increasing Donor Chimerism
If >50% donor and >20% increase since day +28,
Or
if >80% donor on day +28 and >10% increase in donor cells
|
ANY
|
Continue to observe at monthly intervals for progression of chimerism, disease response and GvHD.
|
Stable Mixed Chimera
Donor engraftment subsequent to day +56 not fulfilling the above definitions
|
CR/no evidence of disease
|
DLI
|
|
Evidence of disease
|
DLI
|
ANY Evidence of Disease Activity
|
Early disease progression (prior to day +56)
|
Treatment failure
Chemotherapy or DLI as needed
|
Graft Rejection
|
ANY
|
Consider second transplant
|
Note:
- Patients with GvHD should not be offered DLI.
- DLIs are not to be irradiated.
- Analysis of DLI products is required for T cell subsets (CD3). Notify surface marker laboratory (ext 80917).
- Assess GvHD and CBC/ONCO fortnightly until day +90 after last DLI and monthly thereafter or as indicated. Document GvHD status at day +90 and day +365 after last DLI.
- If GvHD develops – see GvHD section.
- Chimerism monitoring is required at Day +28 (PB) and Day +56 (PB) after each DLI.
- Disease evaluation:
- If persistent or progressive disease pre-DLI, evaluate at days 28 and 56 after each DLI.
- If CR achieved, evaluate at 4, 6, 12, 18, and 24 months, annually thereafter.
Work-Up Prior to DLI
- Evaluate disease status.
- Check chimerism:
- If 100%, recheck if more than 6 months since the last report.
- If not 100%, check if more than 2 months since the last report.
- GvHD assessment: if no clinical evidence of GvHD and more than 6 months since last assessment, then repeat tests - lung function, oral health, liver function, ECHO.
Doses, Collection and Administration of DLI
- The following describes a plan for collection and sequential administration of DLI in a dose escalation scheme designed to avoid using higher doses of T cells than those required to eradicate the malignant clone. The rationale for this dose escalation schema includes prior reports that indicate T-cell dose is associated with the risk of GvHD after DLI and may also correlate with disease response.
- Each patient will receive up to 3 intravenous infusions of donor T cells at a starting dose of 1 x 10^6 CD3/kg (sibling donor) or 5 x 10^5 CD3/kg (unrelated donor). Increasing (1/2 log) cell doses are given at intervals of 8-12 weeks if appropriate.
- Donors will undergo leucopheresis and collection of non-mobilised PBMC on the day of the first DLI. Immunophenotyping of the PBMC product will be performed by the stem-cell lab, and will include T cells and their subsets, monocytes, and NK cells. The projected yield of T cells (CD3+) is expected to be in the range of 1.6 x 10^7 CD3/kg. After determining the CD3+ cell content the first dose of T cells will be infused. Residual cells will be cryopreserved for subsequent doses if possible. Additional apheresis will be undertaken to obtain cells at higher dose levels only after eligibility for higher T cell doses are confirmed.
- Collections will be performed first thing in the morning to allow immunophenotyping of product to determine appropriate volume of cells to be infused and cryopreserved. For DLI using fresh PBMC, infusion will take place in the Haematology Dayward in the afternoon of the day of the PBMC collection. Infusions of cryopreserved PBMC should be performed as per standard practice for outpatient PBSC/DLI infusions.
- For dose level 3, serial leucopheresis may be required and daily leucopheresis will be performed until the CD3+ cell total is achieved. Infusions of PBMC will be given on the same day as leucopheresis is performed. Therefore, patients may receive PBMC transfusions given over several days to achieve the planned CD3+ cell dose.
- Un-irradiated DLI will be administered by IV infusion over 30 minutes.
- Paracetamol, pethidine, or chlorphenamine IV 10 mg Q6H, or loratidine 10 mg PO 1-2 times daily, or promethazine 20-50 mg PO max of 75 mg per day may be administered (as needed) for chills. Steroids should be avoided whenever possible.
Note: Donor-specific DLI harvest schedules and patient-specific DLI infusion schedules are available.
Further Reading
Marks, D. I., et al. (2002). "The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation." Blood 100(9): 3108-3114.
Topic Code: 8939
Disclaimer