Tacrolimus and ATG as GVHD Prophylaxis in Patients Undergoing Related Donor HSCT

• Proportion of aGVHD graded according to the Glucksberg criteria [ Time Frame: During the first 6 months post-transplant ] [ Designated as safety issue: No ]
  aGVHD is defined as any GVHD occurring within the first 100 days after transplant
  
  
• Safety of tacrolimus and anti-thymocyte globulin [ Time Frame: Within the first 6 months post-transplant ] [ Designated as safety issue: Yes ]
  Defined by serious adverse events (SAE) related to this immunosuppressive regimen. Except for stopping rule for safety concern, no statistical analysis will be performed for this endpoint.
  
  

• Proportion of chronic GVHD [ Time Frame: Within 2 years after transplant ] [ Designated as safety issue: No ]
  
• Time to engraftment: time to neutrophil (> 500) and platelet (> 25K) count recovery [ Time Frame: At days 10-12 post-transplant ] [ Designated as safety issue: No ]
  
• Overall and disease-free survival [ Time Frame: At 2 years post PBSCT ] [ Designated as safety issue: No ]
  
• Incidence of opportunistic infections, including fungal, and viral (CMV and EBV reactivation including PTLD) [ Time Frame: At weekly intervals beginning around day 21 and until day 100 post-transplant ] [ Designated as safety issue: No ]
  
• Biomarkers and immunocorrelative studies [ Time Frame: At baseline, 30, 60, 90, and 180 days post transplant ] [ Designated as safety issue: No ]
  

PRIMARY OBJECTIVES:

I. To determine the incidence and severity of acute GVHD (aGVHD) following human leukocyte antigen (HLA) matched related donor hematopoietic peripheral blood transplant in patients with hematologic malignancies that receive the immunosuppressive combination of Tacrolimus and Thymoglobulin (anti-thymocyte globulin) as GVHD prophylaxis.

II. To determine the safety of this combination in the first six months post transplant.

SECONDARY OBJECTIVES:

I. To determine engraftment time of neutrophils (absolute neutrophil count > 0.5 x 10^9/L for 3 consecutive days), and platelets (platelet count > 20 X 10^9/L for 3 consecutive days).

II. To determine incidence of opportunistic infections, defined as infection that occurs in people with weakened immune systems and caused by an organism that does not normally cause disease. These include: fungal infections, pneumocytics carinii pneumonia (PCP), and viral infections (cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV], BK virus [BK], Epstein-Barr virus [EBV], including post-transplant lymphoproliferative disorder [PTLD]).

III. To estimate incidence of chronic GVHD (cGVHD) at two years. IV. To determine overall and disease free survival at two years. V. To assess immune response with immunocorrelative studies both pre and at various points post transplant.

OUTLINE:

GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) continuously or orally (PO) on days -3 to 60 with taper to day 100 (high-risk disease) or on days -3 to 100 with taper to day 180 (low-risk disease). Patients also receive anti-thymocyte globulin IV over 4-6 hours on days -3 to -1.

PREPARATIVE REGIMEN: Patients receive standard of care (at the Karmanos Cancer Institute) preparative regimens chosen by the treating physician, based on diagnosis.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

After completion of study treatment, patients are followed up for 2 years.