Relapsed Malignant Blood Cancer After Allogeneic Hematopoietic Stem Cell Transplantation

• 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.