Relapsed Hematologic Malignancy After Allogeneic Hematopoietic Stem Cell Transplantation: Screening, Disease Characterization and Natural History

Inclusion Criteria

- INCLUSION CRITERIA:

RECIPIENT SUBJECTS:

1. Individuals who are candidates for allotransplant therapy for hematologic
malignancies and are being evaluated at the Clinical Center for planned
allotransplantation.

2. Individuals who have received allotransplant treatment for hematologic malignancy.

Potential subjects will be evaluated for participation on one of two cohorts.
Following hematologic recovery after allotransplant (defined in No. 2, below),
individuals have:

1. Relapse Cohort: Cancer progression, relapse or persistently stable (unremitting)
cancer; or

2. Remission (Control) Cohort: Cancer that is responding or in remission at/after
Day 100 post-allotransplant.

Note: subjects who enroll during screening for allotransplant will be assigned to one
of these two cohorts based on the results of their Day 100 (3-month) post-SCT visit
or at first progression of cancer, if before Day 100.

3. Hematologic recovery after allotransplant: neutrophil recovery to 500 cells/ml.
Secondary cytopenias or cytopenias due to disease progression will be permitted.
Note: this requirement will not apply to subjects enrolling pre-SCT.

4. An ongoing relationship with a primary oncologist who will continue to provide
continuity of care during and after study participation.

5. Following record review and information exchange between the patient's primary
oncologist and the NCI PI/LAI/Designee, the PI/LAI/Designee determines that the
individual reasonably could be expected to safely tolerate travel to and from the CC
to undergo evaluation as defined in the protocol, in the event that the patient is
ineligible or uninterested in participating in open treatment protocols.

6. 0-99 years.

7. Ability of individual or parent/legal guardian to give informed consent.

DONOR SUBJECTS:

1. Individuals who are/will be the donors of allogeneic hematopoietic stem cell
transplants received by Recipient-Subjects who are to be enrolled on this protocol.

2. Age 0-99 years. Note: minor subjects (age < 18 years) will be eligible for
enrollment only if they will be undergoing a therapeutic cell collection on another
protocol. Specifically, allocation of cells collected in excess of clinical
requirements for research under this study is permitted, but pediatric donor subjects
will not undergo studies and/or sample collections, or re-collection of cells
intended exclusively for research under this protocol.

3. Ability of donor or parent/legal guardian to give informed consent.

4. Adequate venous access for peripheral apheresis, or (adults) consent to use a
temporary central venous catheter for apheresis.

5. Individuals with evidence of infection with transfusion-transmittable agents
(Hepatitis B and C Viruses (HBV, HCV); Human Immunodeficiency Virus (HIV ), Human
TLymphotrophic Virus (HTLV I/II), West Nile Virus (WNV) and Trypanosoma cruzi) will
not be excluded from study participation. However, Donor-Subjects with evidence of
HIV infection will only be able to donate cells for research. Donors with a history
of HBV or HCV infection will be able to donate for research, and may be eligible to
donate for therapeutic administration. However, determination of permissibility for
clinical donation will require a hepatology consultation and the consent of the
intended recipient after discussion of the risk/benefit of the donor cell product and
the possibility/consequences of transmission. The PI/LAI/Designee will make the final
determination of permissibility of donation for recipient cell therapy.

6. Unrelated donor selection will be in accordance with the National Marrow Donor
Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor
product from an NMDP Center is identified, the recipient will complete an NMDP search
transfer request to allow NIH NMDP staff to contact the NMDP Coordinating Center, who
will, in turn, contact the donor's prior Donor Center. The NMDP Policy for Subsequent
Donation Requests will be followed and the appropriate forms (Subsequent Donation
Request Form and Therapeutic T Cell Collection Prescription Form) will be submitted
as required.

EXCLUSION CRITERIA:

RECIPIENT SUBJECTS:

1. Individuals with rapid disease progression or aggressive cancer histology who, in the
opinion of the PI/LAI/Designee, require urgent therapy within 30 days in order to
preserve organ function or quality of life. This restriction will not apply if there
is no approved therapy with a reasonable chance of disease response, if the patient
does not have access to an effective therapy and the patient appears to be eligible
for an accruing CC treatment protocol or if the patient is enrolled on an NIH/CC
clinical protocol, e.g., allotransplant protocol.

2. Pregnancy or lactating. Additionally, Recipient-Subjects of childbearing potential
that will receive cancer treatment under this protocol must be willing to use an
effective method of contraception.

DONOR SUBJECTS:

1. Hypertension that is not controlled by medication, stroke, or severe heart disease
(donors with symptomatic angina will be excluded). Donor-Subjects with a history of
coronary artery bypass grafting or angioplasty who are symptom-free may receive a
cardiology evaluation and be considered on a case-by-case basis.

2. Pregnancy. Additionally, Donor-Subjects of childbearing potential must be willing to
use an effective method of contraception (Section 4.8) until after completion of
apheresis. Potential fetal risks of apheresis, with or without use of exogenous
hematopoietic growth factors, are unknown. Lactating donors will be eligible provided
they are willing to express and discard milk that is produced while receiving
exogenous hematopoietic growth factors. The quantity of excretion into breast milk
during receipt of exogenous growth factors is unknown and its safety has not been
evaluated in breast-fed infants.

3. History of prior malignancy. Donor-Subjects with a history of prior malignancy will
not be able to donate cells for therapeutic administration. Exceptions may be made
for individuals who have a history of low-risk cancers that have been fully resected
(e.g., nonmelanomatous skin cancers, carcinoma-in-situ, etc.) and/or cancer survivors
who have undergone potentially curative therapy and have had no evidence of that
disease for at least five years; these individuals may be considered for therapeutic
cell donation on a case-by-case basis. Donor-Subjects who are not able to donate
cells for therapeutic administration may participate in cell collections intended for
research.

4. Anemia (Hb < 11 gm/dl) or thrombocytopenia (platelets < 100,000/microL). However,
potential donors with Hb levels < 11 gm/dl due to iron deficiency will be eligible
as long as the donor is initiated on iron replacement therapy. The NIH Clinical
Center, Department of Transfusion Medicine will determine the appropriateness of
anemic individuals as donors. Anemic donors who are not able to donate cells for
therapeutic administration may participate in cell collections intended for research.

5. Adult donors who are not eligible for clinical donation will not be excluded from
study participation, but will only be able to donate cells for research.