Treatment of Graft Failure After Hematopoietic Stem Cell Transplantation

Treatment of Graft Failure After Hematopoietic Stem Cell Transplantation

This is a guideline for the treatment of graft failure after hematopoietic stem cell transplant (HSCT). This regimen, consisting of cyclophosphamide and fludarabine with low dose total body irradiation (TBI) is designed to promote donor engraftment by day 42 after initial graft failure.

The graft will consist of bone marrow or G-CSF mobilized peripheral blood from a haploidentical related donor. The source of stem cells will be determined by the transplant team based on factors such as patient's age, medical history, donor availability and will be according to the current University of Minnesota Blood and Marrow Transplantation Program selection guidelines.

Inclusion Criteria:

• Patients with primary or secondary graft failure, as defined below, may receive a second transplant:

  • Primary graft failure is defined as not achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42 following the first transplant.
  • Secondary graft failure is defined as achieving an ANC ≥0.5x10^9/L for three consecutive days by day 35 - 42, but subsequently drops below 0.5x10^9/L without recovery.
  • Loss of chimerism is defined as achieving an ANC ≥0.5x10^9/L for three consecutive, but with less than 10% CD15+ donor cells in the marrow or peripheral blood.

• Recipients should have acceptable organ function defined as:

  • Renal: creatinine < 2.0 (adults) and creatinine clearance > 30. For creatinine clearance < 70, consultation with a BMT pharmacist is necessary for chemotherapy dose adjustments.
  • Hepatic: bilirubin, AST/ALT, ALP < 10 x upper limit of normal
  • Cardiac: left ventricular ejection fraction > 40%

Exclusion Criteria:

• Uncontrolled infection at the time of transplant.
• Patients with Fanconi Anemia or other DNA breakage syndromes.