Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer

• Quantification of HIV-1-specific immune response [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  Quantitative plasma HIV RNA will be determined by a branched-chain DNA based assay and CD4+ and CD8+ T cell subsets will be evaluated by flow cytometry.
• Quantification of latent HIV reservoir [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  Latent HIV will be detected in leukapheresis product using sensitive culture techniques and assessed by the log change in HIV-1 latent reservoir, measured as IUPM (infectious units per million).

• Quantification of HIV-1-specific immune response [ Time Frame: One year ] [ Designated as safety issue: No ]
• Quantification of latent HIV reservoir [ Time Frame: One year ] [ Designated as safety issue: No ]

• Number of participants who die from HIV-associated mortality [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
• Number of participants who receive continuous as opposed to disrupted HAART [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  Defined by number of days off HAART.
• Number of patients who have undetectable viral load after HCT [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  Defined by number of days without evidence of HIV-1 mRNA (viral load).

• HIV-associated mortality [ Time Frame: One year ] [ Designated as safety issue: Yes ]
• Feasibility of continuous HAART after conditioning [ Time Frame: Number of days off HAART ] [ Designated as safety issue: Yes ]
• Feasibility of controlling HIV-1 replication post-HCT [ Time Frame: Number of days without evidence of HIV-1 mRNA (viral load) ] [ Designated as safety issue: Yes ]

This phase II trial studies the immune response after stem cell transplant in human immunodeficiency virus (HIV)-positive patients with hematologic cancer. Studying samples of blood from HIV-positive patients with cancer in the laboratory may help doctors learn more about changes that occur in the immune system after stem cell transplant

PRIMARY OBJECTIVES:

I. To examine the development of donor-derived HIV-1-specific immune response following hematopoietic cell transplant (HCT) for treatment of hematologic malignancy in HIV+ patients.

II. To examine the affect of HCT on the pool of latently infected cluster of differentiation (CD)4+ T cells in HIV+ patients given HCT for treatment of hematologic malignancy.

SECONDARY OBJECTIVES:

I. To determine mortality caused by HIV-related events following HCT in HIV+ patients.

II. To determine feasibility of continuous HAART administration after conditioning, defined by number of days off highly active antiretroviral therapy (HAART).

III. Examine control of HIV-1 replication after HCT, defined by number of days without evidence of HIV-1 messenger ribonucleic acid (mRNA) (viral load).

OUTLINE:

Patients undergo leukapheresis for analysis of HIV-1 latent reservoir at baseline and at days +90, +180, +365, and +730. Patients receive conditioning regimen, undergo either allogeneic or autologous marrow or peripheral blood stem cell transplantation, and receive graft-vs-host disease prophylaxis according to standard medical procedures. Patients undergo blood sample collection periodically for biomarker analysis.

• Accelerated Phase Chronic Myelogenous Leukemia
• Adult Acute Lymphoblastic Leukemia in Remission
• Adult Acute Myeloid Leukemia in Remission
• Adult Nasal Type Extranodal NK/T-cell Lymphoma
• AIDS-related Diffuse Large Cell Lymphoma
• AIDS-related Diffuse Mixed Cell Lymphoma
• AIDS-related Diffuse Small Cleaved Cell Lymphoma
• AIDS-related Immunoblastic Large Cell Lymphoma
• AIDS-related Lymphoblastic Lymphoma
• AIDS-related Peripheral/Systemic Lymphoma
• AIDS-related Small Noncleaved Cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Blastic Phase Chronic Myelogenous Leukemia
• Childhood Acute Lymphoblastic Leukemia in Remission
• Childhood Acute Myeloid Leukemia in Remission
• Childhood Burkitt Lymphoma
• Childhood Chronic Myelogenous Leukemia
• Childhood Diffuse Large Cell Lymphoma
• Childhood Immunoblastic Large Cell Lymphoma
• Childhood Myelodysplastic Syndromes
• Childhood Nasal Type Extranodal NK/T-cell Lymphoma
• Chronic Myelomonocytic Leukemia
• Chronic Phase Chronic Myelogenous Leukemia
• de Novo Myelodysplastic Syndromes
• HIV-associated Hodgkin Lymphoma
• Juvenile Myelomonocytic Leukemia
• Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Adult Burkitt Lymphoma
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Adult Diffuse Mixed Cell Lymphoma
• Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
• Recurrent Adult Immunoblastic Large Cell Lymphoma
• Recurrent Adult Lymphoblastic Lymphoma
• Recurrent Adult T-cell Leukemia/Lymphoma
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Childhood Anaplastic Large Cell Lymphoma
• Recurrent Childhood Large Cell Lymphoma
• Recurrent Childhood Lymphoblastic Lymphoma
• Recurrent Childhood Small Noncleaved Cell Lymphoma
• Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
• Recurrent Grade 3 Follicular Lymphoma
• Recurrent Mantle Cell Lymphoma
• Secondary Myelodysplastic Syndromes

• Procedure: leukapheresis
  Undergo leukapheresis
• Procedure: allogeneic hematopoietic stem cell transplantation
  Undergo allogeneic HSCT
• Procedure: autologous hematopoietic stem cell transplantation
  Undergo autologous HSCT
• Procedure: peripheral blood stem cell transplantation
  Undergo PBSCT
  Other Names:

  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
• Other: laboratory biomarker analysis
  correlative study
• Other: DNA analysis
  correlative study
• Other: RNA analysis
  correlative study
• Other: flow cytometry
  correlative study
• Other: reverse transcriptase-polymerase chain reaction
  correlative study
  Other Name: RT-PCR
• Other: nucleic acid sequencing
  correlative study
  Other Names:

  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
• Other: protein expression analysis
  correlative study

Inclusion Criteria:

• HIV positive
• Treatment with HAART for at least 1 month
• Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy

• Hematologic malignancy associated with a poor prognosis with medical therapy alone - diagnoses to be included:

  • Acute Myeloid Leukemia in first remission, second remission, or relapse
  • Acute Lymphoblastic Leukemia in first remission, second remission, or relapse
  • Chronic Myeloid Leukemia in accelerated phase or blast phase. Chronic phase is allowed if patient has not achieved a cytogenetic remission or has developed unacceptable toxicity to medical therapy, such as tyrosine kinase inhibitor therapy
  • Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
  • Myeloproliferative disorders, including Chronic Myelomonocytic Leukemia (CMML), Agnogenic Myeloid Metaplasia with Myelofibrosis, Juvenile CML, or unclassified myeloproliferative disorders
  • Hodgkin Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference
  • Non-Hodgkin Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference
• Approval for allogenic regimen given at Patient Care Conference
• Additional inclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional required inclusion criteria; eligibility criteria for patients enrolled at other institutions may be determined by the Institutional Primary Research protocol in lieu of criteria listed above
• DONOR: Autologous peripheral blood with CD34+ cell dose of > 3.0 x 10^6 cells per kilogram recipient weight; autologous recipients are allowed to proceed to nonmyeloablative allogeneic HCT on protocol 1410
• DONOR: Related donor matched for at least 9 of 10 human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 alleles
• DONOR: Unrelated donor matched for at least 9 of 10 HLA-A, B, C, DRB1, and DQB1 alleles and willing to donate either marrow or peripheral blood stem cells; the acceptable level of the single mismatch is defined as an allele level mismatch at HLA-DRB1 or an antigen level mismatch at HLA-A, B, C, or DQB1
• DONOR: Donor inclusion criteria may be expanded in the case where the patient is also enrolled on a separate Institutional Review Board (IRB)-approved Primary Research Protocol; please refer to the Primary Research Protocol for Donor Inclusion Criteria

Exclusion Criteria:

• Positive serology for toxoplasma gondii AND requiring treatment or with evidence of active infection
• A medical history of noncompliance with HAART or medical therapy
• Serum creatinine > 2 times upper limit of normal (ULN)
• Serum bilirubin greater than 3 times the ULN unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 times the ULN, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome
• Forced vital capacity (FVC), forced expiratory volume (FEV)1 or diffusing capacity of the lung for carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
• Cardiac insufficiency or coronary artery disease requiring treatment
• Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
• Karnofsky performance score < 70
• Cardiac insufficiency or coronary artery disease requiring treatment
• Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
• Karnofsky performance score < 70
• Patients capable of conceiving a child and unwilling to use procedures to prevent conception
• Pregnancy or patients actively breastfeeding
• Additional exclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional exclusion criteria
• DONOR: HIV positive
• DONOR: Medical or psychological reason that would make donor procedure intolerable
• DONOR: Age > 75 years
• DONOR: Medical history, physical exam, or laboratory findings that indicate donation would entail excess risk to donor or patient; this includes, but is not limited to pregnancy, history of autoimmune disorder, thromboembolism, serious adverse reaction to anesthesia, current treatment with lithium or monoclonal antibodies or any experimental drug, laboratory findings of hemoglobinopathy, thrombocytopenia, or blood borne pathogens; any unrelated donor must have approval by the Donor Center after evaluation by history and physical

• National Cancer Institute (NCI)
• National Institute of Allergy and Infectious Diseases (NIAID)