Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

Modified Preemptive CMV Management Strategy After Allogeneic Hematopoietic Cell Transplantation and Laboratory Correlation With Innate Immune Function

RATIONALE: Infection prophylaxis and management may help prevent cytomegalovirus (CMV) infection caused by a stem cell transplant.

PURPOSE:This clinical trial studies infection prophylaxis and management in treating cytomegalovirus infection in patients with hematologic malignancies previously treated with donor stem cell transplant.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy and safety of a individualized strategy for cytomegalovirus (CMV) preemptive management, one that monitors CMV viral load and clinical markers of immunosuppression to optimize use of ganciclovir in recipients of allogeneic hematopoietic cell transplantation (HCT) who experience CMV reactivation.

SECONDARY OBJECTIVES:

I. To investigate how donor killer-cell immunoglobulin-like receptors (KIR) genes of interest (activating KIR2DS2 and 2DS4, inhibitory KIR2DL1, 2DL2/2DL3, 3DL1, 3DL2), together with their recipient ligands where known, influence CMV reactivation-free survival after allogeneic HCT, independently of clinical risk factors such as onset of acute graft-versus-host disease.

II. To investigate whether markers of natural killer (NK) cell function correlate with a) KIR/ligand compound genotype and baseline or concurrent clinical factors and b) with history of CMV reactivation and anti-CMV therapy at the time of NK cell collection.

III. To investigate associations between NK cell recovery and antigen-specific T cell immune reconstruction.

OUTLINE: Patients receive standard antiviral infection prophylaxis and management comprising ganciclovir, valganciclovir, or foscarnet sodium for 2 weeks or until the plasma CMV deoxyribonucleic acid (DNA) quantitative polymerase chain reaction (Q-PCR) is negative. Patients may receive additional courses based on subsequent CMV reactivations.

After completion of study treatment, patients are followed up for up to 1 year.

Inclusion Criteria:

• Diagnosis: hematologic malignancies/disorders including aplastic anemia and myelodysplastic syndrome
• Procedure: first allogeneic, T cell-replete transplantation of stem-cells from peripheral blood or bone marrow of an human leukocyte antigen (HLA) matched, unrelated or nonsyngeneic sibling donor
• CMV seropositive donor and/or recipient
• Performance level: must have already been determined to be eligible for HCT at City of Hope (COH)
• Organ function requirements: The minimum organ function requirements should be the same as the requirements for HCT
• Informed Consent: All patients must be capable of signing a written informed consent and no consent can be provided by a legal guardian

Exclusion Criteria:

• The recipient had prior polymerase chain reaction (PCR) positive CMV infection in blood or organ-specific disease in the past 12 months
• The source of hematopoietic stem cells is T-cell depleted
• Concomitant anti-graft-versus-host disease (GVD) treatment includes in vivo T cell depletion
• Recipient is human immunodeficiency virus (HIV)-1 positive
• No prior allogeneic HCT (Allo HCT) (autologous HCT [Auto HCT] is allowed)