Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation
Partially HLA-Matched Irradiated Allogeneic Cellular Therapy After Reduced Intensity Total Body Irradiation
RATIONALE: Giving low-dose total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant after total-body irradiation and to see how well it works in treating patients with relapsed or refractory hematologic cancer or acute myeloid leukemia or acute lymphocytic leukemia in complete remission.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients undergo low-dose total-body irradiation and infusion of irradiated donor cells on day 0. Patients also receive filgrastim subcutaneously (SC) daily or pegfilgrastim SC every 14 days starting on day 1.
Patients in complete remission (CR) or with persistent disease undergo irradiated donor lymphocyte infusion (DLI) at 8 weeks. Repeat irradiated DLI is administered if patients remain in CR or achieve stable or responding disease after the second infusion (if confirmed by histologic assessment) or third infusion (if confirmed by radiographic assessment). DLI repeats every 8 weeks pending disease and clinical status up to a total of 6 infusions over a 12-month period.
Blood samples are collected at baseline, upon recovery of counts, and then monthly thereafter for immunologic studies.
After completion of study treatment, patients are followed up periodically.
DISEASE CHARACTERISTICS:
Patients over 18 years old must meet the following criteria:
Histologically confirmed hematologic malignancy and not a candidate for a standard allogeneic transplantation
High-risk disease, including:
Patients 13-17 years old must meet the following criteria:
Histologically confirmed hematologic malignancy and not a candidate for a standard allogeneic transplantation
High-risk disease, including:
Eligible for haploidentical irradiated cellular therapy
No known active brain metastases or malignant meningitis
Available partially (≥ 3/6 class I antigen) HLA-matched (by serology) related donor NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-2
Karnofsky PS 60-100% (for patients > 16 years) or Lansky PS 60-100% (for patients ≤ 16 years)
Patients ≥ 18 years:
Patients 13-17 years:
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
AST/ALT ≤ 2.5 times ULN for age
Total bilirubin < 2.0 mg/dL (unless attributable to Gilbert syndrome)
Shortening fraction ≥ 27% by ECHO or ejection fraction ≥ 50% by radionuclide angiogram
FEV_1, forced vital capacity, and DLCO corrected for hemoglobin ≥ 60% by pulmonary function tests (PFTs)
Children unable to cooperate for PFTs must meet the following criteria:
Any other organ dysfunction thought to be secondary to disease will be considered separately and the patient will be eligible at the physician's discretion
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception before, during, and for 24 weeks after study treatment
No known HIV positivity
No history of current or prior medical problems that, in the investigator's opinion, would prevent administration of study treatment or assessment of response due to excess toxicity
No active uncontrolled infections or other medical, psychological, or social conditions that might increase the likelihood of patient adverse effects or poor outcomes
PRIOR CONCURRENT THERAPY: