Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
- Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated
allogeneic stem cell transplantation for a hematological malignancy.
- For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia
chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least
two measurements over a 6 month interval. If cytogenetics are normal and there is
PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of
a quantitative increase in CML measured either by quantitative PCR or by fluorescent
in situ hybridization (FISH).
- For non-CML, relapse will be defined based on disease specific morphologic criteria
from a bone marrow biopsy and aspirate or recurrence of disease specific
cytogenetics. For disease specific definition of relapse, see appendix 3. Relapse
can be determined morphologically with less than 5 percent blasts if definitive
relapse can be determined. Equivocal results for relapse should result in a repeated
test after an appropriate time interval (suggested 1 month) to determine eligibility.
Post-transplant lymphoproliferative diseases (often referred to as EBV-associated
lymphomas) are NOT eligible for this protocol.
- For Chronic Phase CML patients only
- - must have failed (no response in 3 months or incomplete response at 6 months) or
refused treatment with Gleevec
- - if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI
with chemotherapy per this protocol will be offered
- Patients must be within one year of identification of relapse or if beyond that time
period, must have at least 10% donor DNA by RFLP or cytogenetics.
- Same allogeneic donor (sibling or URD) used for transplantation is available for
- No severe organ damage (by laboratory or clinical assessment) as measured by:
- - blood creatinine ≤ 2.0 mg/dL
- - liver function tests < 5 x normal
- - left ventricular ejection fraction > 40% (testing required only if symptomatic or
prior known impairment).
- - pulmonary functions > 50% (testing required only if symptomatic or prior known
impairment). Oxygen saturation (>92%) can be used in child where PFT's cannot be
- - chest x-ray without evidence of active infection
- Off prednisone and other immunosuppressive agents (given for any reason) for at
least 3 days prior to DLI infusions.
- Performance status ≥ 60%
- Women must not be pregnant or lactating. The agents used in this study may be
teratogenic to a fetus and there is no information on the excretion of agents into
breast milk All females of childbearing potential must have a blood test or urine
study within 2 weeks prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males are strongly advised to use
an accepted and effective method of contraception
- Patient must given written informed consent indicating understanding of the nature of
the treatment and its potential risks
- Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing
treatment at the time of relapse will be ineligible.
- Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other
immunosuppressive medications are not eligible until these medications are
discontinued for at least 2 weeks without a flare of GVHD.
- Active CNS leukemia
- Active fungal infection or pulmonary infiltrates (stable prior treated disease is
- HIV positive