Donor Lymphocyte Infusion After Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

• INCLUSION CRITERIA:

Inclusion Criteria - Recipient

• Histologically or cytologically confirmed hematologic malignancy classified as highor very high disease risk by the Refined Disease Risk Index for HCT including one ofthe following:

• Acute myeloid leukemia (AML) with favorable cytogenetics (t(8;21), inv(16),t(15,17)) with induction failure (persistent disease without first achievingremission of any type) or active relapse

• AML with intermediate cytogenetics (not classified as favorable or adverse) withinduction failure or active relapse (AML with intermediate cytogenetics inmorphologic complete remission [CR] with minimal residual disease detectable by anymodality also will be eligible)

• AML with adverse cytogenetics (complex karyotype with >= 4 abnormalities) regardlessof remission status

• Low risk myelodysplastic syndrome (MDS) (<= 5% blasts, including chronicmyelomonocytic leukemia) with adverse cytogenetics (abnormal chromosome 7 or >= 4abnormalities) with induction failure or active relapse

• High risk MDS (RAEB-1 or RAEB-2) with intermediate-risk cytogenetics (no abnormalchromosome 7 or < 4 abnormalities) with induction failure or active relapse

• High risk MDS (RAEB-1 or RAEB-2) with adverse cytogenetics (abnormal chromosome 7 or >= 4 abnormalities) regardless of remission status

• Acute lymphoblastic leukemia (ALL) in CR >= 2 or with induction failure or activerelapse (ALL in CR1 with minimal residual disease detected also will be eligible)

• Chronic myelocytic leukemia (CML) in blast crisis phase

• Hodgkin lymphoma with stable or progressive disease

• Mantle cell lymphoma with stable or progressive disease

• Relapsed Burkitt lymphoma in CR or partial remission (PR)

• Aggressive B-cell Non-Hodgkin Lymphoma (NHL) (e.g., diffuse large B-cell lymphoma,transformed indolent B-cell lymphoma) with stable or progressive disease

• T-cell NHL with stable or progressive disease

• Multiple myeloma (MM) with induction failure as defined by failure to achieveminimal response (CR, Very Good Partial Response [VGPR], or PR) or the developmentof progressive disease on primary therapy, or MM with active relapse as defined bypreviously treated myeloma that achieved a molecular response or better that thenprogressed

• Age 18-65 years.

• At least one potentially suitable HLA-haploidentical or HLA-matched donor

• Karnofsky performance score >=60%

• Recipient participants must have adequate organ function as defined below:

• Cardiac ejection fraction >=45% by 2D ECHO;

• Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusingcapacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of >=50% predicted;

• Estimated serum creatinine clearance of >=60 ml/minute/1.73m2 calculated using eGFRin the clinical lab;

• Total bilirubin <=2X the upper limit of normal;

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3X the upperlimit of normal.

• Myeloablative conditioning is toxic to the developing human fetus and isteratogenic. For this reason, the following measures apply:

• Women of child-bearing potential (WOCBP) and men must agree to use highly effectivecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for at least one-year post-transplant.

• WOCBP must have a negative serum or urine pregnancy test within 7 days prior toenrollment.

Inclusion Criteria - Donor

-Related donor (age >=12) deemed suitable, eligible, and willing to donate, per clinical evaluations, who are additionally willing to donate blood, bone marrow, and stool for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.

EXCLUSION CRITERIA:

Exclusion Criteria - Recipient

• Subjects who are receiving any other investigational agents. Prior experimentaltherapies must have been completed at least 3 weeks prior to the date of beginningconditioning.

• Prior myeloablative conditioning for autologous or allogeneic HCT.

• Active breastfeeding.

• Active malignancy of non-hematopoietic type (excluding non-melanoma skin cancers)which is metastatic, relapsed/refractory to treatment, or locally advanced and notamenable to curative treatment. This excludes non-melanoma skin cancers.

• Uncontrolled intercurrent illness (e.g. severe endocrinopathy, disseminatedintravascular coagulation, profound electrolyte disturbance, active hepatitis,uncontrolled dental infection) that in the opinion of the PI would make it unsafe toproceed with transplantation.

Exclusion Criteria - Donor

None.