Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
- Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral
blood mononuclear cells (PBMC) after CD34-selected megadose haploidentical
hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers
or other diseases.
- Determine the feasibility of collecting parental allogeneic stimulator cells to induce
anergy to the nonshared donor-recipient haplotype in these patients.
- Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo
- Determine the number of transplanted individuals who meet the criteria for proceeding
to delayed infusion of ex vivo anergized donor PBMC.
- Establish the safety of delayed infusion of ex vivo anergized donor PBMC by
establishing the maximum number of donor T cells that can be infused without
unacceptable graft-versus-host disease.
- Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in
donor PBMC after ex vivo anergization.
- Assess, in vitro, the function of immune cells engrafted in these patients.
- Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these
- Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and
its rate of recovery.
- Describe the patterns of opportunistic infections in these patients.
OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic
peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except
dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).
- Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily
on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7,
fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin
IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo
CD34-selected PBSCT on day 0.
- Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are
free of active uncontrolled infection and graft-vs-host disease, patients undergo
allogeneic or autologous PBMC infusion on day 35 or 42.
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of
5 or 3 of 8 patients experience dose-limiting toxicity.
After completion of study, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Primary Purpose: Treatment
Eva Guinan, MD
Dana-Farber Cancer Institute
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Childrens Hospital Los Angeles||Los Angeles, California 90027|
|M. D. Anderson Cancer Center at University of Texas||Houston, Texas 77030-4009|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|Children's Hospital Boston||Boston, Massachusetts 02115|