Using Multi-virus Cytotoxic T-cells Following T-Cell Depleted Allogeneic HPCT for Prophylaxis Against EBV, ADV, and CMV

This protocol is a phase I study. Patients may be eligible for an infusion of Multi-virus Cytotoxic T Lymphocytes (CTL) if they received a T-cell depleted (TCD) transplant from a related family member or an unrelated donor. Recipients of these types of transplants are severely immune compromised during the early post-transplant period and are more susceptible to certain viruses. The investigators hypothesize that the adoptive transfer of Cytotoxic T Lymphocytes (CTL) against certain viruses: Adenovirus, Cytomegalovirus and Epstein Barr Virus (Ad, CMV, and EBV) will be safe with regard to producing graft versus host disease (GVHD) or other infusion related toxicities.

Within this clinical trial, the investigators will test the hypotheses that the administration of CTLs for prophylaxis against Ad, CMV and EBV in recipients of TCD-HPCT will be safe and well tolerated. Graded doses of Multi-Virus CTL will be administered to recipients of genotypically haploidentical or mismatched unrelated TCD grafts.

Eligibility Criteria:
Inclusion Criteria:

* Patient age \< 22 years.
* Both genders and all races are eligible.
* The patient population chosen for the T-cell depleted allogeneic HPCT from a related or unrelated allogeneic donor must meet eligibility based on institutional SOPs and/or the IRB approved T cell depleted allogeneic HPCT protocol which they are enrolled.
* Must be willing to sign a written informed consent.
* Patient Organ Status at the time of enrollment (pre-transplant)

  * Lansky or Karnofsky score \> 50
  * Echocardiogram shortening fraction \> 27%
  * Renal function: serum creatinine \< 2 x normal for age
  * DLCO \> 50% predicted in patients old enough to comply with PFTs or no baseline oxygen requirement for younger patients.
  * Hepatic: AST, ALT \< 5x upper limit of normal; bilirubin \< 2.0 mg/dl
* Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months following CTL infusion. The male partner should use a condom.
* Patients must be between 28 and 100 days post T-cell depleted allogeneic HPCT
* Patients must meet the following criteria (within 72 hours of CTL infusion):

  * Achieved primary engraftment with an ANC of at least 1000 per μl for 3 consecutive days.
  * No oxygen requirement with oxygen saturations \> 90%.
  * AST, ALT \< 5x upper limit of normal for age; bilirubin \< 2 mg/dl.
  * Hemoglobin \> 8 gm/dl prior to infusion. (May be transfusion dependent).
  * Renal function: serum creatinine \< 2 x normal for age.
* The Patient must not have the following conditions on the day of CTL infusion:

  * Exhibit overt hematologic manifestations of relapse or persistent disease.
  * Evidence of recurrent/persistent disease based primarily on flow cytometry, cytogenetics, chimerism analysis, or other molecular studies does not by itself represent grounds for exclusion.

Exclusion Criteria:

* Currently enrolled on another Phase I clinical trial.
* Pregnant or nursing
* Overt hematologic manifestations of relapse or persistent disease
* Having \> grade 1 graft-versus-host disease.