Donor Lymphocyte Infusion After Alternative Donor Transplantation

Phase 1

Terminated

Brief Summary: The purpose of this study is to determine the ability of a donor lymphocyte infusion (DLI) given with methotrexate to hasten immune recovery without causing severe graft-versus-host disease (GVHD) in recipients who have had a T-cell depleted transplant.

Detailed Description: Studies have shown that giving donor T cells after a mismatched T cell-depleted stem cell transplant can speed up recovery of T cells in the patient. This approach can cause severe graft versus host disease (GVHD). The purpose of this study is to determine whether giving a donor lymphocyte infusion (DLI) with methotrexate can accelerate immune recovery in recipients of T cell-depleted stem cell transplants. Thirty days after a T-cell depleted transplant, patients will be given a DLI. They will be monitored for immune recovery as measured by CD4 count and for GVHD toxicity.

Patients will be separated into six cohorts based on dose of DLI received: 3 x 10\^4, 4 x 10\^4, 5 x 10\^4, 6 X 10\^4, 8 x 10\^4, and 10 X10\^4 cells/ kg of body weight. A minimum of 3 patients will be tested at each dose starting with the lowest dose. Dose escalation will continue until the dose associated with CD4 count \>100 at Day +120 after transplant without significant GVHD is determined. All patients will receive thirteen doses of methotrexate after the DLI to prevent GVHD. Patients will be followed for 2 years for outcomes.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Active GVHD at the time when DLI are due
History of acute GVHD > grade I prior to DLI
Disease due to viral infection (eg. CMV) when DLI are due (asymptomatic viral replication or viral shedding is not a contraindication)
Uncontrolled bacterial or fungal infection
O2 saturation by pulse oximetry < 95%
Bilirubin > 3mg/dL or ALT > 5 x upper limit of normal
Creatinine > 3x baseline (at transplant)
ANC (WBC x % neutrophils + bands) < 500/ul
Significant effusions (eg. pleural or pericardial) or ascites
EBV-related PTLD
Persistent or increasing mixed chimerism requiring therapeutic DLI as defined on the LCH BMT 09-01 protocol

Arm && Interventions

Group	Intervention	Description
Infusion of donor lymphocytes	Infusion of donor lymphocytes	Patients will receive an infusion of donor lymphocyte after T-cell depleted transplant.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Immune Recovery Following Transplantation	120 days after transplant	Immune recovery was measured by CD4+ cells \> 100/μL by Day 120 following transplantation
Incidence and Severity of GVHD	180 days after transplant	Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)	1 year	Subjects were actively monitored for adenovirus, cytomegalovirus (CMV), human herpes virus 6 (HHV6), and Epstein-Barr virus (EBV) as part of standard post-transplant care. All infections were collected from date of DLI until 1 year after transplant.