Eligibility Details:
Inclusion Criteria:
- Must have a human leukocyte antigen (HLA)-matched or single allele-mismatched adult
sibling serving as donor
- Must have a myeloid or lymphoid malignant disease that is treated with TLI and ATG
reduced intensity conditioning for allogeneic transplant (any of the following AML,
myelodysplastic syndrome [MDS], myeloproliferative disease [MPD], CLL, B or T-cell
NHL, HL)
- Patients who due to age, pre-existing medical conditions, or, prior therapy are
considered to be at high risk for regimen related toxicity associated with fully
ablative transplant conditioning, and therefore reduced intensity conditioning is
recommended
- Ability to understand and the willingness to sign a written informed consent document;
patients must have signed informed consent to participate in the trial
- DONOR: Must be an HLA-matched or single allele mismatched sibling of enrolled
transplant patient
- DONOR: Must be 18-75 years of age, inclusive
- DONOR: Must be in a state of general good health and have completed a donor evaluation
with history, medical examination and standard blood tests within 35 days of starting
the hematopoietic cell collection procedure; in order to fairly represent the
interests of the donor, the donor evaluation and consent will be performed by a study
team member other than the recipient's attending physician
- DONOR: Must have a white blood cell count > 3.5 x 10^9/liter, platelets > 150 x
10^9/liter and hematocrit > 35%
- DONOR: Must be capable of undergoing leukapheresis
- DONOR: Must be able to understand and sign informed consent
- DONOR: Must not be seropositive for HIV 1 and 2, hepatitis B surface antigen,
hepatitis C antibody, human T-lymphotropic virus (HTLV) antibody, cytomegalovirus
(CMV) immunoglobulin M (IgM), or rapid plasma reagin (RPR) (Treponema); donors with
prior evidence of hepatitis B core antibody positivity will have a polymerase chain
reaction (PCR) test done to evaluate for hepatitis B infection; donors with a positive
hepatitis B PCR test are excluded
- DONOR: Females must not be pregnant or lactating
- DONOR: Must not have psychological traits or psychological or medical conditions which
make them unlikely to tolerate the procedure
- DONOR: Must not have developed a new malignancy requiring chemotherapy or radiation in
the interval since apheresis for initial hematocrit (HCT)
- PATIENT CRITERIA FOR PROCEEDING WITH CD8+ MEMORY T-CELL INFUSION:
- Patients must be beyond day 30 and before day 60 after transplant
- Patients must have evidence of mixed CD3 T-cell chimerism based on the day +28 (+/- 7
days) blood sample showing >= 5% and =< 95% donor type cells
- Patients must have no evidence of active graft-versus-host disease at the time of the
CD8+ memory T-cell infusion; patients with a history of acute GVHD overall grade II
based on skin only involvement or upper gastrointestinal (GI) tract involvement only
will be eligible; patients with a history of liver or lower GI tract GVHD will not be
eligible
- Patients must be on single immune suppression therapy with either tacrolimus or
cyclosporine at the time of CD8+ memory T-cell infusion; prednisone at a physiologic
dose of 5 mg per day or less is allowed
- Patients must have a Karnofsky performance status of >= 60% at the time of the CD8+
memory T-cell infusion
- Patients must not have an uncontrolled bacterial, fungal or viral infection, defined
as progressive symptoms despite therapy, at the time of the CD8+ memory T-cell
infusion; asymptomatic viremia is allowed
- Patients must have adequate organ function and performance status at the time of the
CD8+ memory T-cell infusion, defined by the following:
- Total bilirubin =< 4 mg/dL
- SGOT or SGPT =< 4 x ULN
- Creatinine =< 3 mg/dL or estimated creatinine clearance >= 40ml/min
Exclusion Criteria:
- Uncontrolled bacterial, viral or fungal infection defined as currently taking
medication and progression of clinical symptoms
- Progressive hemato-lymphoid malignancy despite conventional therapy
- Acute leukemia not in remission
- Chronic myelogenous leukemia (CML)
- Active central nervous system (CNS) involvement of the underlying malignancy
- Human immunodeficiency virus (HIV) positive
- Pregnant or lactating
- Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR
treated =< 5 years ago but have a greater than 50% chance of life expectancy of >= 5
years for that malignancy)
- Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of
the primary physician would place the patient at an unacceptable risk from transplant
- Ejection fraction < 30%, or uncontrolled cardiac failure
- Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% predicted
- Total bilirubin > 3 mg/dL
- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
transaminase (SGPT) > 4 x upper limit of normal (ULN)
- Creatinine > 2 mg/dL and an estimated creatinine clearance =< 40 mL/min
- Poorly controlled hypertension despite multiple antihypertensive medication OR
- Karnofsky performance status (KPS) < 60%
- Note: Patients positive for hepatitis B and C will be evaluated on a case by case
basis